Characterization of the Inflammatory Response to Severe COVID-19 Illness.

Rationale: Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood.Objectives: To define the cytokine profile of COVID-19 and to identify evidence of immunometabolic alterations in those with severe illness.Methods: Levels of IL-1ß, IL-6, IL-8, IL-10, and sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed in plasma from healthy volunteers, hospitalized but stable patients with COVID-19 (COVIDstable patients), patients with COVID-19 requiring ICU admission (COVIDICU patients), and patients with severe community-acquired pneumonia requiring ICU support (CAPICU patients). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of AAT (alpha-1 antitrypsin) to COVID-19 was also evaluated.Measurements and Main Results: IL-1ß, IL-6, IL-8, and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVIDstable patients, and demonstrated higher levels of IL-1ß, IL-6, and sTNFR1 but lower IL-10 than CAPICU patients. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, HIF-1α (hypoxia-inducible factor-1α), and lactate. The production and sialylation of AAT increased in COVID-19, but this antiinflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P < 0.0001). In critically unwell patients with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6:AAT was associated with clinical resolution (P < 0.0001).Conclusions: The COVID-19 cytokinemia is distinct from that of other types of pneumonia, leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population.

Management of donation after brain death (DBD) in the ICU: the potential donor is identified, what's next?

The success of any donation process requires that potential brain-dead donors (PBDD) are detected and referred early to professionals responsible for their evaluation and conversion to actual donors. The intensivist plays a crucial role in organ donation. However, identification and referral of PBDDs may be suboptimal in the critical care environment. Factors influencing lower rates of detection and referral include the lack of specific training and the need to provide concomitant urgent care to other critically ill patients. Excellent communication between the ICU staff and the procurement organization is necessary to ensure the optimization of both the number and quality of organs transplanted. The organ donation process has been improved over the last two decades with the involvement and commitment of many healthcare professionals. Clinical protocols have been developed and implemented to better organize the multidisciplinary approach to organ donation. In this manuscript, we aim to highlight the main steps of organ donation, taking into account the following: early identification and evaluation of the PBDD with the use of checklists; donor management, including clinical maintenance of the PBDD with high-quality intensive care to prevent graft failure in recipients and strategies for optimizing donated organs by simplified care standards, clinical guidelines and alert tools; the key role of the intensivist in the donation process with the interaction between ICU professionals and transplant coordinators, nurse protocol managers, and communication skills training; and a final remark on the importance of the development of research with further insight into brain death pathophysiology and reversible organ damage.

Blood biocompatibility of surface-bound multi-walled carbon nanotubes.

Blood clots when it contacts foreign surfaces following platelet activation. This can be catastrophic in clinical settings involving extracorporeal circulation such as during heart-lung bypass where blood is circulated in polyvinyl chloride tubing. Studies have shown, however, that surface-bound carbon nanotubes may prevent platelet activation, the initiator of thrombosis. We studied the blood biocompatibility of polyvinyl chloride, surface-modified with multi-walled carbon nanotubes in vitro and in vivo. Our results show that surface-bound multi-walled carbon nanotubes cause platelet activation in vitro and devastating thrombosis in an in vivo animal model of extracorporeal circulation. The mechanism of the pro-thrombotic effect likely involves direct multi-walled carbon nanotube-platelet interaction with Ca(2+)-dependant platelet activation. These experiments provide evidence, for the first time, that modification of surfaces with nanomaterials modulates blood biocompatibility in extracorporeal circulation.

Acute kidney injury in cardiac surgery.

PURPOSE OF REVIEW: Acute kidney injury (AKI) is a long-recognized complication of cardiac surgery. It is a commonly encountered clinical syndrome that, in its most severe form, increases the odds of operative mortality three to eight-fold. The pathogenesis of cardiac surgery-associated acute kidney injury (CSA-AKI) is complex. No single intervention is likely to provide a panacea, and thus, the purpose of this review is to assess the wide breadth of emerging research into potential strategies to prevent, diagnose, and treat CSA-AKI. RECENT FINDINGS: Research in the field of CSA-AKI published within the last 18 months adds further layers of knowledge to many previously studied areas. These include its definition (Risk, Injury, Failure, Loss, End-stage kidney disease, Acute Kidney Injury Network, and Kidney Disease: Improving Global Outcomes criteria), diagnosis (biomarkers and intraoperative renal oximetry), prevention (statin therapy, acetylsalicylic acid, N-acetylcysteine, sodium bicarbonate, off-pump coronary revascularization, goal-directed hemodynamic therapy, and minimizing blood transfusion), and treatment (early initiation of renal replacement therapy). SUMMARY: Although there has been much high-quality research conducted in this field in recent years, preventing CSA-AKI by avoiding renal insults remains the mainstay of management. Although biomarkers have the potential to diagnose CSA-AKI at an earlier stage, efficacious interventions to treat established CSA-AKI remain elusive.

Critical care in pregnancy--is it different?

In the first part of this review, the epidemiology of obstetric critical care is discussed. This includes the incidence of severe morbidity in pregnancy, identification of critically ill and potentially critically ill patients, the incidence of obstetric ICU admissions, the type of critical illness by stage of pregnancy, ICU admission diagnoses, the severity of illness in obstetric ICU patients compared to non-obstetric patients, ICU mortality of obstetric patients, the ICU proportion of total maternal mortality, and the causes of death for obstetric patients in ICU. In the second part, the management of obstetric patients who happen to be admitted to a general ICU is discussed. Rather than focusing on the management of particular obstetric conditions, general principles of ICU management will be discussed as applied to obstetric ICU patients. These include drug safety, monitoring the fetus, management of the airway, sedation, muscle relaxation, ventilation, cardiovascular support, thromboprophylaxis, and radiology and ethical issues.