Liberal transfusion strategy to prevent mortality and anaemia-associated, ischaemic events in elderly non-cardiac surgical patients - the study design of the LIBERAL-Trial.

BACKGROUND: Perioperative anaemia leads to impaired oxygen supply with a risk of vital organ ischaemia. In healthy and fit individuals, anaemia can be compensated by several mechanisms. Elderly patients, however, have less compensatory mechanisms because of multiple co-morbidities and age-related decline of functional reserves. The purpose of the study is to evaluate whether elderly surgical patients may benefit from a liberal red blood cell (RBC) transfusion strategy compared to a restrictive transfusion strategy. METHODS: The LIBERAL Trial is a prospective, randomized, multicentre, controlled clinical phase IV trial randomising 2470 elderly (≥ 70 years) patients undergoing intermediate- or high-risk non-cardiac surgery. Registered patients will be randomised only if Haemoglobin (Hb) reaches ≤9 g/dl during surgery or within 3 days after surgery either to the LIBERAL group (transfusion of a single RBC unit when Hb ≤ 9 g/dl with a target range for the post-transfusion Hb level of 9-10.5 g/dl) or the RESTRICTIVE group (transfusion of a single RBC unit when Hb ≤ 7.5 g/dl with a target range for the post-transfusion Hb level of 7.5-9 g/dl). The intervention per patient will be followed until hospital discharge or up to 30 days after surgery, whichever occurs first. The primary efficacy outcome is defined as a composite of all-cause mortality, acute myocardial infarction, acute ischaemic stroke, acute kidney injury (stage III), acute mesenteric ischaemia and acute peripheral vascular ischaemia within 90 days after surgery. Infections requiring iv antibiotics with re-hospitalisation are assessed as important secondary endpoint. The primary endpoint will be analysed by logistic regression adjusting for age, cancer surgery (y/n), type of surgery (intermediate- or high-risk), and incorporating centres as random effect. DISCUSSION: The LIBERAL-Trial will evaluate whether a liberal transfusion strategy reduces the occurrence of major adverse events after non-cardiac surgery in the geriatric population compared to a restrictive strategy within 90 days after surgery. TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT03369210 ).

6% Hydroxyethyl starch (HES 130/0.4) diminishes glycocalyx degradation and decreases vascular permeability during systemic and pulmonary inflammation in mice.

BACKGROUND: Increased vascular permeability is a pathophysiological hallmark of sepsis and results in increased transcapillary leakage of plasma fluid, hypovolemia, and interstitial edema formation. 6% hydroxyethyl starch (HES 130/0.4) is commonly used to treat hypovolemia to maintain adequate organ perfusion and oxygen delivery. The present study was designed to investigate the effects of 6% HES 130/0.4 on glycocalyx integrity and vascular permeability in lipopolysaccharide (LPS)-induced pulmonary inflammation and systemic inflammation in mice. METHODS: 6% HES 130/0.4 or a balanced electrolyte solution (20 ml/kg) was administered intravenously 1 h after cecal ligation and puncture (CLP) or LPS inhalation. Sham-treated animals receiving 6% HES 130/0.4 or the electrolyte solution served as controls. The thickness of the endovascular glycocalyx was visualized by intravital microscopy in lung (LPS inhalation model) or cremaster muscle (CLP model). Syndecan-1, hyaluronic acid, and heparanase levels were measured in blood samples. Vascular permeability in the lungs, liver, kidney, and brain was measured by Evans blue extravasation. RESULTS: Both CLP induction and LPS inhalation resulted in increased vascular permeability in the lung, liver, kidney, and brain. 6% HES 130/0.4 infusion led to significantly reduced plasma levels of syndecan-1, heparanase, and hyaluronic acid, which was accompanied by a preservation of the glycocalyx thickness in postcapillary venules of the cremaster (0.78 ± 0.09 µm vs. 1.39 ± 0.10 µm) and lung capillaries (0.81 ± 0.09 µm vs. 1.49 ± 0.12 µm). CONCLUSIONS: These data suggest that 6% HES 130/0.4 exerts protective effects on glycocalyx integrity and attenuates the increase of vascular permeability during systemic inflammation.

Intra- versus postoperative initiation of pain control via a thoracic epidural catheter for lumbar spinal fusion surgery.

BACKGROUND: Thoracic epidural anesthesia (TEA) is one of the pillars of perioperative pain care. Particularly for spine surgery which causes significant postoperative pain TEA seems like an appealing option. However, beneficial effects of a TEA are questionable when the catheter is not used intraoperatively, a decision that is usually based on the surgeon's wish to perform immediate neurological examination postoperatively. METHODS: Forty patients undergoing transforaminal lumbar interbody fusion surgery (TLIF) were randomized into two groups. Patients received preoperative insertion of a TEA. For patients in the intraoperative group an epidural infusion was started preoperatively and maintained throughout. For patients in the postoperative group the epidural infusion was started once neurological examination had been performed. The primary outcome measure in this study was postoperative requirements of piritramide during the first two postoperative hours. Secondary outcomes involved postoperative pain numeric rating scale (NRS) scores, intraoperative opioid requirements, side effects and ability to perform direct postoperative neurological examination. RESULTS: Postoperative group patients required significantly more opioids both intra- and postoperatively (P=0.036 and P=0.039) and NRS scores were significantly higher on admission to recovery, at 30 and 60 min as compared to patients in the intraoperative group (P=0.013; P=0.004 and P=0.012). Early postoperative neurological examination was feasible in all patients in both groups. CONCLUSIONS: Epidural catheters used intraoperatively during TLIF are feasible, significantly reduce pain, intra- and postoperative use of opioids and do not influence the quality of neurological tests directly after the surgical procedure.

Long-Term Clinical Outcomes after Early Initiation of RRT in Critically Ill Patients with AKI.

Whether earlier initiation of RRT in critically ill patients with AKI can improve outcomes remains debated. We examined follow-up data from a large clinical trial to prospectively investigate the long-term outcomes associated with the timing of RRT initiation in such patients. We extended the follow-up of patients in the Early Versus Delayed Initiation of RRT in Critically Ill Patients with AKI (ELAIN) Trial from 90 days to 1 year after randomization for 230 (99.6%) patients. The primary outcome was a composite of major adverse kidney events (persistent renal dysfunction, dialysis dependence, and mortality) at 1 year. Secondary outcomes included inflammatory markers. Overall, 72 of 111 (64.9%) and 106 of 119 (89.1%) patients met the primary outcome in the early (stage 2 AKI) and delayed (stage 3 AKI) initiation groups, respectively (odds ratio [OR] with early initiation, 0.23; 95% confidence interval [95% CI], 0.11 to 0.45; P< 0.001). The early initiation group had a 1-year all-cause mortality rate (56 of 111 [50.2%]) significantly lower than that of the delayed initiation group (83 of 119 [69.8%]; absolute difference, -19.6%; 95% CI, -32.0% to -7.2%; P<0.01). After 1 year, 16 of 55 (29.1%) and 23 of 36 (63.9%) surviving patients in the early and delayed groups, respectively, failed to recover renal function (absolute difference, -34.8%; 95% CI, -54.6% to -15.0%; P=0.001). In conclusion, early initiation of RRT in these critically ill patients with AKI significantly reduced the occurrence of major adverse kidney events, reduced mortality, and enhanced renal recovery at 1 year.

[Ultrasound in regional anesthesia]. / Ultraschall in der Anästhesie und Intensivmedizin - Ultraschall in der Regionalanästhesie.

The ultrasound in regional anesthesia is gaining currency. Of fundamental importance for a successful blockade is not only the direct process. Many decisions taken in advance, have enormous impact on the quality of implementation. The aim of this article is about the current state of knowledge on implementing instructions of the risk stratification, hygiene, choice of the needle, the training and the sequence concerning ultrasound regional anesthesia. There are pitfalls and presented important conditions for successful work with this method.