Explore the vast range of titles available.

BackgroundPreliminary reports have described significant procoagulant events in patients with coronavirus disease-2019 (COVID-19), including life-threatening pulmonary embolism (PE).Main textWe review the current data on the epidemiology, the possible underlying pathophysiologic mechanisms, and the therapeutic implications of PE in relation to COVID-19. The incidence of PE is reported to be around 2.6–8.9% of COVID-19 in hospitalized patients and up to one-third of those requiring intensive care unit (ICU) admission, despite standard prophylactic anticoagulation. This may be explained by direct and indirect pathologic consequences of COVID-19, complement activation, cytokine release, endothelial dysfunction, and interactions between different types of blood cells.ConclusionThromboprophylaxis should be started in all patients with suspected or confirmed COVID-19 admitted to the hospital. The use of an intermediate therapeutic dose of low molecular weight (LMWH) or unfractionated heparin can be considered on an individual basis in patients with multiple risk factors for venous thromboembolism, including critically ill patients admitted to the ICU. Decisions about extending prophylaxis with LMWH after hospital discharge should be made after balancing the reduced risk of venous thromboembolism (VTE) with the risk of increased bleeding events and should be continued for 7–14 days after hospital discharge or in the pre-hospital phase in case of pre-existing or persisting VTE risk factors. Therapeutic anticoagulation is the cornerstone in the management of patients with PE. Selection of an appropriate agent and correct dosing requires consideration of underlying comorbidities.

Keywords: COVID-19, ICU, SARS-CoV-2

The cardiovascular system plays a key role in sepsis, and septic myocardial depression is a common finding associated with increased morbidity and mortality. Myocardial depression during sepsis is not clearly defined, but it can perhaps be best described as a global (systolic and diastolic) dysfunction of both the left and right sides of the heart. The pathogenesis of septic myocardial depression involves a complex mix of systemic (hemodynamic) factors and genetic, molecular, metabolic, and structural alterations. Pulmonary artery catheterization and modern echo-Doppler techniques are important diagnostic tools in this setting. There are no specific therapies for septic myocardial depression, and the cornerstone of management is control of the underlying infectious process (adequate antibiotic therapy, removal of the source) and hemodynamic stabilization (fluids, vasopressor and inotropic agents). In this review, we will summarize the pathogenesis, diagnosis, and treatment of myocardial depression in sepsis. Additional studies are needed in order to improve diagnosis and identify therapeutic targets in septic myocardial dysfunction.

Opposite to the angiotensin-converting enzyme (ACE)/Ang II axis, RAS has a counter-regulatory axis, which is composed by angiotensin-(1–7) (Ang 1–7) and ACE2 [2]. Since ACE2 can minimize the risk of acute lung injury, a recombinant form of human ACE2 (rhACE2) has been tested in patients with ARDS in a recent phase II trial [2]; this study showed that rhACE2 increases surfactant protein D concentrations without major side effects. [...]ECMO patients need an adequate accurate anti-coagulation for the integrity of the extracorporeal system. [...]we would argue that a theoretical improvement in oxygenation, as suggested by animal studies, is less relevant during ECMO when oxygenation is provided via the extracorporeal circuit.

Recently, an international randomized controlled trial (ATHOS-3) [1] has shown that Ang II can induce a significant increase in mean arterial pressure (MAP) if compared to placebo. [...]during the first 48 hours from the randomization, doses of the vasopressors (norepinephrine (NE) and vasopressin) were significantly reduced in the Ang II group but not in the placebo group. According to the case of the nonselective nitric oxide synthase inhibitor [5], Ang II could reduce the cardiac output due to its preferential vasoconstrictive action and provide some detrimental effects for those patients with myocardial dysfunction. [...]Ang II significantly increased the heart rate (HR) in the ATHOS-3 trial.

Critically ill patients frequently require analgesic and sedative medications to manage pain, agitation, and the stress associated with their condition. The onset of Acute Kidney Injury (AKI) can complicate the pharmacokinetics of these drugs, requiring careful dose adjustments to prevent adverse effects. Additionally, Kidney Replacement Therapy (KRT) may further influence drug metabolism and clearance. As renal dysfunction may alter the elimination of these medications, a comprehensive understanding of their pharmacologic profiles and the impact of KRT is essential for optimizing pain and sedation management in critically ill patients. In particular, this review explores the challenges and strategies involved in dosing analgesic and sedative drugs in critically ill patients with AKI undergoing various KRT modalities, including intermittent hemodialysis (IHD), continuous kidney replacement therapy (CKRT), and prolonged intermittent kidney replacement therapy (PIKRT). Moreover, this narrative review is aimed at summarizing existing evidence on pharmacokinetic alterations, clearance rates and eventual dose adjustments in critically ill patients with AKI undergoing various KRT modalities. Special emphasis is placed on the effects of different KRT modalities on drug elimination and associated therapeutic implications, seeking to provide healthcare professionals with evidence-based guidelines for the safe and effective administration of analgesics and sedatives in this complex, high-risk patient population.

[...]there is a need to validate these composite SPs in large observational and prospective studies, to avoid the biases inherent to retrospective studies. [...]we suggest that a prompt identification of different SPs could facilitate the patient stratification in the era of individualized medicine. Authors Sample size (n.) Population Type of SPs Classification Findings Shald4 et al. 320 ICU septic patients Clinical presentation SP 1: MOF SP 2: ND SP 3: RD SP 4: other patients SP 1 showed higher mortality rate Bhavani6et al. 12,473 Patients with sepsis/suspected infection Clinical presentation SP A: higher temperature, HR, RR SP B: lower temperature, HR, RR SP C: older patients SP D: older patients, high doses of vasopressors SP A and D showed higher mortality rate Seymour5 et al. 20,189 Septic patients Clinical presentation SP α: low doses of vasopressors SP β: older patients SP γ: higher rate of inflammation and RD SP δ: LD and septic shock SP δ showed higher mortality rate Seymour1 et al. 191 Animal study Inflammatory status/laboratory alterations Class 1:hypoinflamatory profile Class 2:hyperinflammatory profile Class 2 showed a rapid clinical deterioration Carcillo2 et al. 100 Pediatric study Inflammatory status/laboratory alterations Type 1. immune paralysis + MOF Type 2: thrombocytopenia + MOF Type 3: LD + MOF Type 2 showed higher mortality rate Kudo3 et al. 3696 ICU septic shock patients Inflammatory status/laboratory alterations Cluster dA: severe coagulopathy Cluster dB: moderate coagulopathy Cluster dC: mixed cases Cluster dD: mixed cases Treatment with rhTM lower mortality rate in clusters with severe coagulopathy Table 1 Classification of septic phenotypes based on current literature.

We reviewed the different studies using the terms “refractory septic shock” and/or “catecholamine resistance” and/or “high dose norepinephrine” so as to highlight the heterogeneity of the definitions used by authors addressing such concepts. A systematic review was conducted assessing the papers reporting data on refractory septic shock. We used keywords as exact phrases and subject headings according to database syntax. Of 276 papers initially reviewed, we included 8 studies – 3 randomized controlled trials, 3 prospective studies and 2 retrospective studies, representing a total of 562 patients with septic shock. Catecholamine resistance was generally defined as “a decreased vascular responsiveness to catecholamine independently of the administered norepinephrine dose”. Refractory septic shock was broadly defined as “a clinical condition characterized by persistent hyperdynamic shock even though adequate fluid resuscitation (individualized doses) and high doses of norepinephrine (≥ 1 μg/kg/min)”. Reported “high doses” of norepinephrine were often ≥1 μg/kg/min. However, wide variability was found throughout the literature on the use of these terms. Marked inconsistencies were identified in the usage of the terms for refractory septic shock. There is a pressing need to determine consensus definitions so as to establish a common language in the medical literature and to harmonize future studies. •The terms “catecholamine resistance”, “refractory septic shock” and “high dose norepinephrine” are often used in the literature.•Catecholamine resistance was generally defined as “a decreased vascular responsiveness to catecholamine independently of the administered norepinephrine dose”.•Refractory septic shock was “a clinical condition characterized by persistent hyperdynamic shock even though adequate fluid resuscitation (individualized doses) and high doses of norepinephrine (≥ 1 μg/kg/min)”.•Reported “high doses” of norepinephrine were often ≥1 μg/kg/min.•Wide variability was found throughout the literature on the use of these terms.