Measurement of the balance between nociception and anti-nociception during anaesthesia is challenging and not yet clinically established. The Surgical pleth index (SPI), derived from photoplethysmography, was proposed as a surrogate measure of nociception. Recently, the analgesia nociception index (ANI) derived by heart rate (HR) variability was developed. The aim of the present study was to challenge the ability of ANI compared with SPI to detect standardized noxious stimulation during propofol–remifentanil anaesthesia. After Ethics approval and informed consent, 25 patients were anaesthetized with propofol [bispectral index (BIS) 30–60]. A laryngeal mask (LMA) was inserted and remifentanil stepwise increased to effect-site concentrations (Ce_remi) of 0, 2, and 4 ng ml⁻¹. At each step, tetanic stimulation (STIM) was applied. ANI, SPI, BIS, HR, and mean arterial pressure (MAP) were obtained before and after LMA insertion and each STIM. Analysis was performed using Wilcoxon rank tests and calculation of prediction probabilities (P_K). ANI and SPI, but not BIS, HR, or MAP, were significantly (P<0.05) changed at all examined steps. ANI response to STIM was (median [IQR]) −24 [−12–35], −30 [−20–−40] and −13 [−5–−27] at 0, 2 and 4 ng ml⁻¹ Ce_remi. However, prediction of movement to STIM was not better than by chance, as P_K values were 0.41 (0.08) for ANI and 0.62 (0.08) for SPI. The two variables, ANI and SPI, enabled consistent reflection of stimulation during propofol–remifentanil anaesthesia. Nevertheless, ANI and SPI may improve detection but not prediction of a possible inadequate nociception–anti-nociception balance. Clinicaltrials.gov Identifier. NCT01522508.

Evaluation of analgesia and antinociception during anaesthesia is still a challenging issue and routinely based on indirect and non-specific signs such as movement, tachycardia, or lacrimation. Recently, the surgical pleth index (SPI) derived by finger plethysmography was introduced to detect nociceptive stimulation during anaesthesia. While SPI guidance reduced the number of unwanted events during total i.v. anaesthesia (TIVA), the impact of SPI during volatile-based anaesthesia with intermittent opioid administration has not yet been elucidated. Ninety-four patients were randomized into either SPI-guided analgesia or standard practice (Control). In both groups, anaesthesia was maintained with sevoflurane to keep bispectral index values between 40 and 60. In the SPI group, patients received a sufentanil bolus (10 μg) whenever SPI value increased above 50, whereas in the control group, sufentanil was administered according to standard clinical practice. The number of unwanted somatic events, haemodynamics, sufentanil consumption, and recovery times were recorded. The incidence of intraoperative unwanted somatic events was comparable between the groups (P=0.89). No significant differences with respect to hypotensive or hypertensive events were found. The mean (95% confidence interval) sufentanil consumption was non-significantly (P=0.07) reduced in the SPI group, 0.64 (0.57–0.71) vs 0.78 (0.64–0.91) µg min⁻¹. Recovery times were comparable between the groups. Sufentanil administration guided by SPI during sevoflurane anaesthesia is clinically feasible. In contrast to TIVA, it did not improve anaesthesia conduct with respect to unwanted somatic events, haemodynamic stability, sufentanil consumption, emergence time, or post-anaesthesia care unit care. Therefore, we conclude that anaesthesia regimen has an impact on beneficial effects by SPI guidance. NCT01525537. (Registered at Clinicaltrials.gov.)

Article: Analgesia/nociception monitoring for opioid guidance: meta-analysis of randomized clinical trials - Minerva Anestesiologica 2017 February;83(2):200-13 - Minerva Medica - Journals

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. 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. 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. ClinicalTrials.gov (identifier: NCT03369210 ).

Remote ischemic preconditioning (RIPC) is a phenomenon, whereby repeated, non-lethal episodes of ischemia to an organ or limb exert protection against ischemia–reperfusion (I/R) injury in distant organs. Despite intensive research, there is still an apparent lack of knowledge concerning the RIPC-mediated mechanisms, especially in the intestine. Aim of this study was to evaluate possible protective effects RIPC on intestinal I/R injury. Thirty rats were randomly assigned to four groups: I/R; I/R + RIPC; Sham; Sham + RIPC. Animals were anesthetized and the superior mesenteric artery was clamped for 30 min, followed by 60 min of reperfusion. RIPC-treated rats received 3 × 5 min of bilateral hindlimb I/R prior to surgery, sham groups obtained laparotomy without clamping. After I/R injury serum/tissue was analyzed for: Mucosal damage, Caspase-3/7 activity, expression of cell stress proteins, hydrogen peroxide (H2O2) and malondialdehyde (MDA) production, Hypoxia-inducible factor-1α (HIF-1α) protein expression and matrix metalloproteinase (MMP) activity. Intestinal I/R resulted in increased mucosal injury (P < 0.001) and elevated Caspase-3/7 activity (P < 0.001). RIPC significantly reduced the histological signs of intestinal I/R injury (P < 0.01), but did not affect Caspase-3/7 activity. Proteome profiling suggested a RIPC-mediated regulation of several cell stress proteins after I/R injury: Cytochrome C (+ 157%); Cited-2 (− 39%), ADAMTS1 (+ 74%). Serum concentrations of H2O2 and MDA remained unchanged after RIPC, while the reduced intestinal injury was associated with increased HIF-1α levels. Measurements of MMP activities in serum and intestinal tissue revealed an attenuated gelatinase activity at 130 kDa within the serum samples (P < 0.001) after RIPC, while the activity of MMPs within the intestinal tissue was not affected by I/R injury or RIPC. RIPC ameliorates intestinal I/R injury in rats. The underlying mechanisms may involve HIF-1α protein expression and a decreased serum activity of a 130 kDa factor with gelatinase activity.