Individualised perioperative blood pressure and fluid therapy in oesophagectomy ­ study protocol for a randomised clinical trial

INTRODUCTION: Oesophagectomy is the mainstay of curative treatment for oesophageal cancer, but it is associated with a high risk of major complications. Goal-directed fluid therapy and individualised blood pressure management may prevent complications after surgery. Extending goal-directed fluid therapy after surgery and applying an individual blood pressure target may have substantial benefit in oesophagectomy. This is a protocol for a clinical trial implementing a novel haemodynamic protocol from the start of anaesthesia to the next day with the patient's own night-time blood pressure as the lower threshold. METHODS: This is a single-centre, single-blind, randomised, clinical trial. Oesophagectomy patients are randomised 1:1 for either perioperative haemodynamic management according to a goal-directed fluid therapy protocol with an individual target blood pressure or for standard care. The primary endpoint is the total burden of morbidity and mortality assessed by the Comprehensive Complication Index 30 days after surgery. Secondary endpoints are complications, reoperations, fluid and vasopressor dosage and quality of life at 90 days after surgery. CONCLUSIONS: The results from this trial provide an objective and easy-to-follow algorithm for fluid administration, which may improve patient-centred outcomes in oesophagectomy patients. FUNDING: The trial is supported by Aarhus University (1,293,400 DKK) and the Novo Nordisk Foundation (625,200 DKK). TRIAL REGISTRATION: EudraCT number: 2021-002816-30.

Near-infrared spectroscopy monitoring during endovascular treatment for acute ischaemic stroke.

Introduction: The aim of endovascular treatment (EVT) for acute ischaemic stroke is to relieve the cerebral tissue hypoxia in the area supplied by the occluded artery. Near-infrared spectroscopy (NIRS) monitoring is developed to assess regional cerebral tissue oxygen haemoglobin saturation (rSO2). We aimed to investigate whether NIRS can detect inter- and intra-hemispheric rSO2 differences during EVT. Patients and methods: In this prospective, observational study, patients undergoing EVT for a proximal intracranial occlusion of the anterior circulation between May 2019 and November 2020, were included. A four-wavelength NIRS monitor (O3® Regional Oximeter (Masimo, Irvine, CA)) was used to measure rSO2 during EVT with sensors placed over the temporal lobes in 20 patients and over the frontal lobes in 13 patients. The Wilcoxon signed-rank test was used to test for inter-hemispheric rSO2 differences after groin puncture and after recanalisation, and intra-hemispheric rSO2 changes before and after recanalisation. Results: In the temporal cohort, no inter-hemispheric rSO2 differences were observed after groin puncture (median [IQR] rSO2 affected hemisphere, 70% [67-73] and unaffected hemisphere, 70% [66-72]; p = 0.79) and after recanalisation. There were no intra-hemispheric rSO2 changes over time. In the frontal cohort, no inter- and intra-hemispheric rSO2 differences or changes were found. Discussion and conclusion: A NIRS monitor could not detect inter- and intra-hemispheric rSO2 differences or changes during EVT, irrespective of the sensor position. It is likely that even with temporal sensor application, a significant proportion of the received NIRS signal was influenced by oxygenation of surrounding tissues.

Efficacy and safety of ceftobiprole in patients aged 65 years or older: a post hoc analysis of three Phase III studies.

Aim: To evaluate the efficacy and safety of ceftobiprole in patients aged ≥65 years. Materials & methods: We conducted a post hoc analysis of three randomized, double-blind, Phase III studies in patients with acute bacterial skin and skin structure infections, community-acquired pneumonia and hospital-acquired pneumonia. Results: Findings for patients aged ≥65 years (n = 633) were consistent with those for the overall study populations, although a trend toward improved outcomes was reported in some subgroups, for example, patients aged ≥75 years with community-acquired pneumonia were more likely to achieve an early clinical response with ceftobiprole than comparator (treatment difference 16.3% [95% CI:1.8-30.8]). The safety profile was similar between treatment groups in all studies. Conclusion: This analysis further supports the efficacy and safety of ceftobiprole in older patients with acute bacterial skin and skin structure infections or pneumonia. Clinicaltrials.gov trial identifiers: NCT03137173, NCT00326287, NCT00210964, NCT00229008.

Lay abstract Infections are a common cause of severe disease and death in older patients. Antibiotic treatment may also be complicated by age-related changes within the body. The present study analyzed results from three large clinical trials that assessed the benefits of the novel antibiotic ceftobiprole in the older population. In patients aged over 65 years with skin infections or with pneumonia acquired either in the community or in a hospital setting, ceftobiprole offered similar benefits to established antibiotics. There was also some preliminary evidence that older patients may respond more quickly to ceftobiprole compared with the other antibiotics used in these studies. Overall, ceftobiprole was well tolerated and will be a useful treatment option for infections in older patients. Clinical trial registration: NCT03137173, NCT00326287, NCT00210964, NCT00229008 (Clinicaltrials.gov).

Additional postoperative cell salvage of shed mediastinal blood in cardiac surgery does not reduce allogeneic blood transfusions: a cohort study.

OBJECTIVES: Does additional postoperative collection and processing of mediastinal shed blood with a cell salvage device reduce the number of allogeneic blood transfusions compared to intraoperative cell salvage alone? METHODS: A single-centre cohort study in which adult patients with coronary artery bypass grafting or aortic valve replacement were allocated to either a C.A.T.S(®) group with intraoperative blood processing only or a CardioPat(®) group with both intra- and postoperative blood processing. The primary endpoint was the number of allogeneic blood transfusions during hospital admission. RESULTS: The study included 99 patients; 50 in the C.A.T.S(®) and 49 in the CardioPat(®) group.There was no difference in the number of red blood cells (RBC) (C.A.T.S(®) group 43 units versus CardioPat(®) 50 units, p=0.74), fresh frozen plasma (C.A.T.S(®) 8 units versus CardioPat(®) 8 units, p=1.00) or platelets (C.A.T.S(®) 5 units versus CardioPat(®) 4 units, p=1.00) transfused during the hospital stay.Cardiac creatinine kinase (CK-MB) and troponin levels did not differ between the groups although a significant time effect (p<0.001) was present. Creatinine kinase (CK) levels were not different between the groups three hours after arrival in the intensive care unit (ICU) (CardioPat(®) group versus C.A.T.S(®) group, p=0.17). But, compared to the C.A.T.S(®) group on the first (350 [232-469] IU/L) and second postoperative days (325 [201-480] IU/L), the increase in CK levels was more in the CardioPat(®) group on the first (431 [286-642] IU/L, p=0.02) and second postoperative days (406 [239-760] IU/L, p=0.05), resulting in a difference between the groups (p=0.04) CONCLUSIONS: Postoperative cell salvage does not reduce transfusion requirements compared to intraoperative cell salvage alone, but results in elevated total CK levels that suggest haemolysis.

Hemodynamics and tissue oxygenation during balanced anesthesia with a high antinociceptive contribution: an observational study.

BACKGROUND: In particular surgical conditions, a balanced anesthesia with a high-antinociceptive contribution is required. This may induce cardiovascular impairment and thus compromise tissue oxygenation. In this prospective observational study, we investigated the hemodynamic stability and tissue oxygen saturation (StO2) in 40 patients with a high-antinociceptive general anesthesia, goal-directed fluid therapy, and norepinephrine. In addition, optimal surgical conditions and safe and fast emergence are pivotal parts of anesthetic management. METHODS: In high-antinociceptive propofol/remifentanil anesthesia with bispectral index (BIS) between 40 and 60, norepinephrine was administered to maintain mean arterial pressure (MAP) above 80% of individual baseline. Fluid was administered if the ∆ plethysmographic waveform amplitude exceeded 10%. Surgical and recovery conditions, hemodynamic responses, and tissue oxygenation were investigated. RESULTS: Mean (SD) StO2 at the left thenar eminence increased from 83 (6)% before to 86 (4)% 20 min after induction of anesthesia (p <0.05). Cardiac index dropped from 3.0 (0.7) to 2.1 (0.4) L min(-1) (p <0.05), MAP from 109 (16) to 83 (14) mm Hg, and heart rate from 73 (12) to 54 (8) bpm (p <0.05). Thirteen out of 40 patients received a fluid bolus. The median (range) norepinephrine administration rate was 0.05 (0.0-0.10) µg kg(-1) min(-1). After complete akinesia in all patients during surgery, a median (IQR) extubation time of 311 (253-386) s was observed. CONCLUSIONS: This high-antinociceptive balanced anesthesia with goal-directed fluid and vasopressor therapy adequately preserved StO2 and hemodynamic homeostasis. TRIAL REGISTRATION: ISRCTN20153044.