The value of a dynamic echocardiographic approach to diastolic dysfunction in intensive care medicine.

Diastolic dysfunction is an underestimated feature in the context of the critically ill setting and perioperative medicine. Advances in echocardiography, its noninvasive, safe and easy use, have allowed Doppler echocardiography to become a cornerstone for diagnosing diastolic dysfunction in clinical practice. The diagnosis of diastolic dysfunction and increased filling pressures is nevertheless complex. Using an echocardiographic assessment and the routine application of preload stress maneuvers during echocardiographic examination can help identify early stages of diastolic dysfunction leading to better management of patients at risk of acute heart decompensation in the perioperative period or during ICU stay.

Role of serum albumin and proteinuria in patients with SARS-CoV-2 pneumonia.

BACKGROUND: Hypoalbuminemia is frequently observed in patients with SARS-CoV-2 infection although its underlying mechanism and relationship with the clinical outcome still need to be clarified. METHODS: We retrospectively evaluated in patients with COVID-19 hospitalised at the Fatebenefratelli-Sacco Hospital in Milan, the prevalence of hypoalbuminemia, its association with the severity of COVID-19, with the levels of C-reactive protein, d-dimer and interleukin-6 and with clinical outcome over a follow-up period of 30 days. Urinalysis was evaluated in a subgroup of patients. RESULTS: Serum albumin levels <30 g/L were found in 105/207 (50.7%) patients at hospital admission. Overall, the median albumin value was 29.5 g/L (IQR 25-32.8). A negative association was found between albumin levels and severity of COVID-19 (P < .0001) and death (P = .003). An inverse correlation was observed between albumin and both C-reactive protein and D-dimer at hospital admission (r = -.487 and r = -.479, respectively; P < .0001). Finally, a positive correlation was found between albumin levels and eGFR (r = .137; P = .049). Proteinuria was observed in 75% of patients with available data and it did not differ between patients with hypoalbuminemia and those with albumin ≥30 g/L (81% and 67%, respectively; P = .09). CONCLUSION: In patients with COVID-19, hypoalbuminemia is common and observed in quite an early stage of pulmonary disease. It is strictly associated with inflammation markers and clinical outcome. The common finding of proteinuria, even in the absence of creatinine increase, indicates protein loss as a possible biomarker of local and systemic inflammation worthwhile to evaluate disease severity in COVID-19.

Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy.

BACKGROUND: Tocilizumab, a humanized monoclonal antibody, targets IL-6 receptors blocking downstream pro-inflammatory effects of IL-6. In preliminary reports it was suggested to be beneficial in patients with severe COVID-19. METHODS: In this open-label prospective study we describe clinical characteristics and outcome of 51 patients hospitalized with confirmed and severe COVID-19 pneumonia treated with tocilizumab intravenously. All patients had elevated IL-6 plasma level (>40 pg/mL) and oxygen saturation <93% in ambient air. Clinical outcomes, oxygen support, laboratory data and adverse events were collected over a follow-up of 30 days. RESULTS: Forty-five patients (88%) were on high-flow oxygen supplementation, six of whom with invasive ventilation. From baseline to day 7 after tocilizumab we observed a dramatic drop of body temperature and CRP value with a significant increase in lymphocyte count (p<0.001). Over a median follow-up time of 34 days from tocilizumab, 34 patients (67%) showed an improvement in their clinical severity class; 31 were discharged; 17 (33%) showed a worsening of their clinical status, of these 14 died (27%). The mortality rate was significantly associated with mechanical ventilation at baseline (83.3% vs 20% of patients on non-invasive oxygen support; p=0.0001). The most frequent side effects were an increase of hepatic enzymes (29%), thrombocytopenia (14%), and serious bacterial and fungal infections (27%). CONCLUSION: Tocilizumab exerts a rapidly beneficial effect on fever and inflammatory markers, although no significant impact on the clinical outcome can be inferred by our results. Critically ill patients seem to have a high risk of serious infections with this drug.

Tethering role of the autonomic nervous system on cardioventilatory coupling.

Hypovolemia and intermittent positive pressure ventilation are conditions that frequently characterize the state of critical illness, but their interaction and resulting cardioventilatory coupling is poorly understood even in healthy humans. We explored heart rate variability, baroreflex activity, and their interaction in an experimental protocol involving twelve mildly hypovolemic healthy subjects during spontaneous breathing and noninvasive positive-pressure ventilation. In seven subjects, an echocardiographic assessment was also performed. Correction of hypovolemia, raising cardiac preload, produced an increase in high-frequency spectral power density of heart rate, left low-frequency spectral power density unchanged but enhanced baroreflex sensitivity. Cardioventilatory coupling was affected by both central blood volume and ventilatory mode and was mainly entrained by the respiratory oscillation. In conclusion, the autonomic nervous system and baroreflex have a significant role in compensating the hemodynamic perturbation due to changes of volemia and ventilatory-induced fluctuations of venous return. They exert an integrative function on the adaptive pattern of cardioventilatory coupling.

Association between left ventricular outflow tract opening and successful resuscitation after cardiac arrest.

BACKGROUND: Survival after cardiac arrest depends on adequate cardiopulmonary resuscitation (CPR). Manual or mechanical external chest compression may be ineffective to restore circulation: structures subjected to external chest compression may differ in forces transfer to intrathoracic structures due to anatomic characteristics and physiological changes. This clinical study aims to assess the association of trans-oesophageal findings during CPR and successful resuscitation. METHODS: Retrospective cohort study. Trans-oesophageal assessment of right ventricular fractional area change, right ventricular outflow tract fractional shortening, left ventricular volumes, ejection fraction, and aortic diameters were performed in refractory out-of-hospital cardiac arrest patients admitted to emergency department for extracorporeal CPR. RESULTS: 19 patients were analyzed. 15 of 19 patients (79%) received venous-arterial extracorporeal membrane oxygenation support. Resuscitation was successful with return of spontaneous circulation or electromechanical activity in 7 patients (group-SUXX) and failed in 12 patients (group-FAIL). 6 patients (32%) were alive at 24 h from the cardiac arrest, one patient (5%) survived to hospital discharge. Left ventricular outflow tract (LVOT) was open during CPR in all patients in group-SUXX and in 1 patient in group-FAIL (p 0.0002). None of the patients with closed LVOT had successful resuscitation. Patients in group-SUXX had a higher ejection fraction (p 0.03), ascending aortic diameter (p 0.04), and survival rate than those in group-FAIL (p 0.015). In a multiple variable Cox's proportional model LVOT opening was the only variable associated with successful resuscitation. CONCLUSIONS: Trans-oesophageal echocardiography can be useful in the emergency setting of cardiopulmonary arrest for discriminating between successful and failing resuscitation.

The Role of Failing Autonomic Nervous System on Life-Threatening Idiopathic Systemic Capillary Leak Syndrome.

Idiopathic systemic capillary leak syndrome (ISCLS) is a rare disease that involves the endothelium and microcirculation, leading to an abrupt shift of fluids and proteins from the intravascular to the interstitial compartment. The consequence of the capillary leakage is a life-threatening hypovolemic shock that can lead to lethal multiple organ dysfunction. The autonomic nervous system (ANS) is central in regulating the cardiovascular response to hypovolemia, but ANS modulation in ISCLS has not yet been investigated. Here, we report ANS activity during acute phase and recovery from a severe ISCLS shock and speculate on the possibility that autonomic mechanisms underlie the pathogenesis of attacks.

Severe Plasmodium falciparum malaria in the intensive care unit: A 6-year experience in Milano, Italy.

BACKGROUND: Severe imported Plasmodium falciparum malaria is a potentially life-threatening disease with a reported mortality rate of 5-10% when patients are admitted to the Intensive Care Unit. METHODS: To retrospectively review the clinical aspects, the value of severity predictive scores and the management of patients with severe P. falciparum malaria admitted to an ICU in Milano, Italy between January 2010 and December 2015. RESULTS: Twelve patients were included: seven were male and five female with a median age of 43 years. All were initially treated with intravenous quinine. Median parasitaemia upon admission was 14,5% (range 1-20%). At the time of ICU admission, 3 patients (25%) had 5 or more World Health Organization criteria for severe malaria while another 6 of them developed one or more of the latter during their stay in ICU. Five required mechanical ventilation because of respiratory failure due to ARDS. Four patients required renal replacement therapy. Three patients underwent blood exchange transfusion. All patients survived. CONCLUSIONS: Our retrospective evaluation of adults patients admitted to the ICU with severe imported P. falciparum malaria demonstrated a favourable outcome. Severity predictive scores currently in use probably overestimate the risk of malaria mortality in patients treated in health care systems of high income countries.