European Society of Anaesthesiology.

Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine.

SummaryMortality after lower limb amputation is high, with UK 30-day mortality rates of 9-17%. We performed a retrospective analysis of factors affecting early and late outcome after lower limb amputation for peripheral vascular disease or diabetic complications at a UK tertiary referral vascular centre between 2003 and 2010. Three hundred and thirty-nine patients (233 male), of median (IQR [range]) age 73 (62-79 [26-92]) years underwent amputation. Thirty-day mortality was 12.4%. On regression modelling, the risk of 30-day mortality was increased in patients of ASA grade ≥ 4 (OR 4.23, 95% CI 2.07-8.63), p < 0.001 and age between 74 and 79 years (OR 3.8, 95% CI 1.10-13.13), p = 0.04 and older than 79 years (OR 4.08, 95% CI 1.25-13.25), p = 0.02. Peri-operative (30-day) mortality for these groups was 23.2%, 13.7% and 18.8%, respectively. Survival and Cox regression analysis demonstrated that long-term mortality was associated with: age 74-79 years (HR 2.15, 95% CI 1.38-3.35), p = 0.001; age > 79 years (HR 2.78, 95% CI 1.82-4.25), p < 0.001; ASA grade ≥ 4 (HR 2.04, 95% CI 1.51-2.75), p < 0.001; out-of-hours operating (HR 1.51, 95% CI 1.08-2.10), p = 0.02; and chronic kidney disease stage 4-5 (1.57, 95% CI 1.07-2.30), p = 0.02. Anaesthetic technique was associated with long-term mortality on survival analysis (p = 0.04), but not when analysed using regression modelling. Mortality after lower limb amputation relates to patient age, ASA, out-of-hours surgery and renal dysfunction. These data support lower limb amputations' being performed during daytime hours and after modification of correctable risk factors.

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.

Background And ObjectivesNociceptin/Orphanin FQ (N/OFQ) is a non-classical endogenous opioid peptide that modulates immune function in vitro. Its importance in inflammation and human sepsis is unknown. The objectives of this study were to determine the relationship between N/OFQ, transcripts for its precursor (pre-pro-N/OFQ [ppNOC]) and receptor (NOP), inflammatory markers and clinical outcomes in patients undergoing cardiopulmonary bypass and with sepsis.MethodsA prospective observational cohort study of 82 patients admitted to Intensive Care (ICU) with sepsis and 40 patients undergoing cardiac surgery under cardiopulmonary bypass (as a model of systemic inflammation). Sixty three healthy volunteers, matched by age and sex to the patients with sepsis were also studied. Clinical and laboratory details were recorded. Polymorph ppNOC and NOP receptor mRNA were determined using quantitative PCR. Plasma N/OFQ was determined using ELISA and cytokines (TNF- α, IL-8, IL-10) measured using radioimmunoassay. Data from patients undergoing cardiac surgery were recorded before, 3 and 24 hours after cardiopulmonary bypass. ICU patients with sepsis were assessed on Days 1 and 2 of ICU admission, and after clinical recovery.Main ResultsPlasma N/OFQ concentrations increased (p<0.0001) on Days 1 and 2 of ICU admission with sepsis compared to matched recovery samples. Polymorph ppNOC (p= 0.019) and NOP mRNA (p<0.0001) decreased compared to healthy volunteers. TNF-α, IL-8 and IL-10 concentrations increased on Day 1 compared to matched recovery samples and volunteers (p<0.0001). Similar changes (increased plasma N/OFQ, [p=0.0058], decreased ppNOC [p<0.0001], increased IL-8 and IL-10 concentrations [both p<0.0001]) occurred after cardiac surgery but these were comparatively lower and of shorter duration.ConclusionsThe N/OFQ system is modulated in ICU patients with sepsis with similar but reduced changes after cardiac surgery under cardiopulmonary bypass. Further studies are required to clarify the role of the N/OFQ system in inflammation and sepsis, and the mechanisms involved.

The optimal dose of intrathecal morphine for postoperative analgesia after major surgery is a matter of debate, with some uncertainty concerning the therapeutic potential and safety of intrathecal morphine in the dose range 0.3-1.0 mg. This randomised double-blind study compared the efficacy and side-effect profile of 0.2 mg and 0.5 mg intrathecal morphine in 70 patients undergoing knee replacement surgery. The primary endpoint was the number of patients requiring rescue analgesia (tramadol) during the first 24 h postoperatively. Secondary endpoints included consumption of tramadol and the incidence of adverse effects. Fewer patients in the 0.5-mg group required rescue analgesia in the first 24 h than in the 0.2-mg group (16 (48%) vs 28 (85%), respectively; p = 0.003). Median (IQR [range]) tramadol consumption was lower in the 0.5-mg group than in the 0.2-mg group (0 (0-100 [0-350]) mg vs 100 (50-100 [0-350]) mg, respectively; p = 0.02). The incidence of adverse effects was similar in both groups. This study has demonstrated that 0.5 mg intrathecal morphine produces better analgesia than 0.2 mg after knee replacement without any increase in side-effects.

In the patient cohorts studied, the BLARt assessment tool was a strong predictor of whether or not patients would be able to walk with a prosthetic limb after surgery. It is simple to administer and could be useful in clinical practice to inform expectations for patients and clinicians. Implications for rehabilitation Patients undergoing lower limb amputation face major physical and psychological challenges after surgery that have a considerable impact on rehabilitation and their ability to walk independently. Many amputees are unable to walk with a prosthetic limb, but there are no validated tools to predict this before surgery. The BLARt is a potentially valuable measure that can predict the likelihood of being unable to walk after amputation. It is simple to use and could be useful to inform patients' and clinicians' expectations before surgery.

Background: The perioperative management of antiplatelet therapy in noncardiac surgery patients who have undergone previous percutaneous coronary intervention (PCI) remains a dilemma. Continuing dual antiplatelet therapy (DAPT) may carry a risk of bleeding, while stopping antiplatelet therapy may increase the risk of perioperative major adverse cardiovascular events (MACE). Methods: Occurrence of Bleeding and Thrombosis during Antiplatelet Therapy In Non-Cardiac Surgery (OBTAIN) was an international prospective multicentre cohort study of perioperative antiplatelet treatment, MACE, and serious bleeding in noncardiac surgery. The incidences of MACE and bleeding were compared in patients receiving DAPT, monotherapy, and no antiplatelet therapy before surgery. Unadjusted risk ratios were calculated taking monotherapy as the baseline. The adjusted risks of bleeding and MACE were compared in patients receiving monotherapy and DAPT using propensity score matching. Results: A total of 917 patients were recruited and 847 were eligible for inclusion. Ninety-six patients received no antiplatelet therapy, 526 received monotherapy with aspirin, and 225 received DAPT. Thirty-two patients suffered MACE and 22 had bleeding. The unadjusted risk ratio for MACE in patients receiving DAPT compared with monotherapy was 1.9 (0.93e3.88), P¼0.08. There was no difference in MACE between no antiplatelet treatment and monotherapy 1.03 (0.31e 3.46), P¼0.96. Bleeding was more frequent with DAPT 6.55 (2.3e17.96) P¼0.0002. In a propensity matched analysis of