The future of intensive care: the study of the microcirculation will help to guide our therapies.

The goal of hemodynamic resuscitation is to optimize the microcirculation of organs to meet their oxygen and metabolic needs. Clinicians are currently blind to what is happening in the microcirculation of organs, which prevents them from achieving an additional degree of individualization of the hemodynamic resuscitation at tissue level. Indeed, clinicians never know whether optimization of the microcirculation and tissue oxygenation is actually achieved after macrovascular hemodynamic optimization. The challenge for the future is to have noninvasive, easy-to-use equipment that allows reliable assessment and immediate quantitative analysis of the microcirculation at the bedside. There are different methods for assessing the microcirculation at the bedside; all have strengths and challenges. The use of automated analysis and the future possibility of introducing artificial intelligence into analysis software could eliminate observer bias and provide guidance on microvascular-targeted treatment options. In addition, to gain caregiver confidence and support for the need to monitor the microcirculation, it is necessary to demonstrate that incorporating microcirculation analysis into the reasoning guiding hemodynamic resuscitation prevents organ dysfunction and improves the outcome of critically ill patients.

Airways management in SARS-COV-2 acute respiratory failure: A prospective observational multi-center study.

Objective: Few studies have reported the implications and adverse events of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units. The aim of the present study was to determine the adverse events related to tracheal intubation in COVID-19 patients, defined as the onset of hemodynamic instability, severe hypoxemia, and cardiac arrest. Setting: Tertiary care medical hospitals, dual-centre study performed in Northern Italy from November 2020 to May 2021. Patients: Adult patients with positive SARS-CoV-2 PCR test, admitted for respiratory failure and need of advanced invasive airways management. Interventions: Endotracheal Intubation Adverse Events. Main variables of interests: The primary endpoint was to determine the occurrence of at least 1 of the following events within 30 minutes from the start of the intubation procedure and to describe the types of major adverse peri-intubation events: severe hypoxemia defined as an oxygen saturation as measured by pulse-oximetry <80%; hemodynamic instability defined as a SBP 65 mmHg recoded at least once or SBP < 90 mmHg for 30 minutes, a new requirement or increase of vasopressors, fluid bolus >15 mL/kg to maintain the target blood pressure; cardiac arrest. Results: Among 142 patients, 73.94% experienced at least one major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 65.49% of all patients undergoing emergency intubation, followed by severe hypoxemia (43.54%). 2.82% of the patients had a cardiac arrest. Conclusion: In this study of intubation practices in critically ill patients with COVID-19, major adverse peri-intubation events were frequent. Clinical Trial registration: www.clinicaltrials.gov identifier: NCT04909476.

Objetivo: Pocos estudios han informado las implicaciones y los eventos adversos de realizar una intubación endotraqueal para pacientes críticos con COVID-19 ingresados ​​en unidades de cuidados intensivos. El objetivo del presente estudio fue determinar los eventos adversos relacionados con la intubación traqueal en pacientes con COVID-19, definidos como la aparición de inestabilidad hemodinámica, hipoxemia severa y paro cardíaco. Ámbito: Hospitales médicos de atención terciaria, estudio de doble centro realizado en el norte de Italia desde noviembre de 2020 hasta mayo de 2021. Pacientes: Pacientes adultos con prueba PCR SARS-CoV-2 positiva, ingresados por insuficiencia respiratoria y necesidad de manejo avanzado de vías aéreas invasivas. Intervenciones: Eventos adversos de la intubación endotraqueal. Principales variables de interés: El punto final primario fue determinar la ocurrencia de al menos 1 de los siguientes eventos dentro de los 30 minutos posteriores al inicio del procedimiento de intubación y describir los tipos de eventos adversos periintubación mayores. : hipoxemia severa definida como una saturación de oxígeno medida por pulsioximetría <80%; inestabilidad hemodinámica definida como PAS 65 mmHg registrada al menos una vez o PAS < 90 mmHg durante 30 minutos, nuevo requerimiento o aumento de vasopresores, bolo de líquidos > 15 mL/kg para mantener la presión arterial objetivo; paro cardiaco. Resultados: Entre 142 pacientes, el 73,94% experimentó al menos un evento periintubación adverso importante. El evento predominante fue la inestabilidad cardiovascular, observada en el 65,49% de todos los pacientes sometidos a intubación de urgencia, seguido de la hipoxemia severa (43,54%). El 2,82% de los pacientes tuvo un paro cardíaco. Conclusión: En este estudio de prácticas de intubación en pacientes críticos con COVID-19, los eventos adversos periintubación mayores fueron frecuentes. Registro de ensayos clínicos: www.clinicaltrials.gov identificador: NCT04909476.

Airways management in SARS-COV-2 acute respiratory failure: A prospective observational multi-center study.

OBJECTIVE: Few studies have reported the implications and adverse events of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units. The aim of the present study was to determine the adverse events related to tracheal intubation in COVID-19 patients, defined as the onset of hemodynamic instability, severe hypoxemia, and cardiac arrest. SETTING: Tertiary care medical hospitals, dual-centre study performed in Northern Italy from November 2020 to May 2021. PATIENTS: Adult patients with positive SARS-CoV-2 PCR test, admitted for respiratory failure and need of advanced invasive airways management. INTERVENTIONS: Endotracheal Intubation Adverse Events. MAIN VARIABLES OF INTERESTS: The primary endpoint was to determine the occurrence of at least 1 of the following events within 30 minutes from the start of the intubation procedure and to describe the types of major adverse peri-intubation events: severe hypoxemia defined as an oxygen saturation as measured by pulse-oximetry <80%; hemodynamic instability defined as a SBP 65 mmHg recoded at least once or SBP < 90 mmHg for 30 minutes, a new requirement or increase of vasopressors, fluid bolus >15 mL/kg to maintain the target blood pressure; cardiac arrest. RESULTS: Among 142 patients, 73.94% experienced at least one major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 65.49% of all patients undergoing emergency intubation, followed by severe hypoxemia (43.54%). 2.82% of the patients had a cardiac arrest. CONCLUSION: In this study of intubation practices in critically ill patients with COVID-19, major adverse peri-intubation events were frequent. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov identifier: NCT04909476.

Brain injury after cardiac surgery.

In patients undergoing cardiac surgery, postoperative brain injury significantly contributes to increase morbidity and mortality and has negative consequences on quality of life and costs. Moreover, over the past years, compelling medical and technological improvements have allowed an even older patients' population, with several comorbidities, to be treated with cardiac surgery; however, the risk of brain injury after such interventions is also increased in these patients. With the aim of improving post-operative neurological outcome, a variety of neuromonitoring methods and devices have been introduced in clinical practice. These techniques allow the assessment of a number of parameters, such as cerebral blood flow, brain embolic events, cerebral cortical activity, depth of anesthesia and brain oxygenation. Some of them have been used to optimize the hemodynamic management of such patients and to select specific therapeutic interventions. Also, various pharmacological and non-pharmacological approaches have been proposed to minimize the incidence of brain injury in this setting. In this review we describe the risk factors and mechanisms of cerebral injury after cardiac surgery and focus on monitoring techniques and clinical strategies that could help clinicians to minimize the incidence of brain injury.

Assessment of microperfusion in sepsis.

Microcirculatory alterations are frequent in sepsis and different mechanisms can be implied and variously studied. The severity of microvascular alterations is associated with organ dysfunction and mortality. The aim of this review is to make an overview of the most actual and used techniques applied on septic humans. We aimed at focus on the impact of different techniques on the evaluation of patients' management and outcome.

Colloids for fluid resuscitation: what is their role in patients with shock?

BACKGROUND: Fluid therapy is widely used in critically ill patients to restore effective intravascular volume and improve organ perfusion. Recent studies have questioned the administration of colloid-based solutions, especially if containing hydroxyethyl starch (HES), in different ICU populations; however, there is still uncertainty on the use of colloids as initial fluid therapy for early resuscitation. METHODS: The aim of this study was to investigate the effect of two different resuscitation fluid strategies on the mortality of patients with shock. In a multicentric (57 ICUs), controlled, open-label trial (from February 2003 to August 2012), the authors randomized patients with signs of acute hypovolemia, defined by the combination of hypotension, evidence of low filling pressures or cardiac index and at least two signs of tissue hypoperfusion (such as altered consciousness, mottled skin, oliguria, lactate levels > 2 mmol/L), to received either a colloid- or crystalloid-based therapy. Both cohorts received maintenance fluids consisting in isotonic crystalloids and albumin in case of severe hypoalbuminemia (<2 g/dL). Exclusion criteria included previous fluid therapy, pregnancy, brain death, extended burns, chronic hemodialysis or liver disease, known coagulopathy, acute anaphylaxis, dehydration and hypotension due to sedative drugs. RESULTS: Among the 6498 eligible patients, 2857 were eventually randomized in one of the two groups. The 28-day mortality was 25.4% in the colloid and 27.0% in the crystalloid group (P=0.26). In the sub-group analysis, similar mortality rates were reported for shock due to hypovolemia, sepsis or trauma. Also, the use of continuous renal replacement therapy was similar between groups (11.0% vs. 12.5%, P=0.19). There were more days alive without mechanical ventilation or vasopressors during the first 7 and 28 days and a lower 90-day mortality in the colloid group. CONCLUSION: These data suggest that mortality was not increased and probably decreased with the use of colloids in different forms of shock requiring early fluid resuscitation. We discussed herein some methodological issues that may explain the discrepancies of this trial with the other studies developed in the same field.

Is two (antibiotics) better than one?

The use of antibiotic therapy combining at least two drugs remains controversial in patients with severe sepsis and septic shock. Some studies have suggested an improvement in patients' outcome with combination therapy over monotherapy, especially in those patients with expected mortality exceeding 25%. Nevertheless, a recent large randomized multicentric clinical trial, comparing the effects of meropenem and moxifloxacin to meropenem alone on the occurrence of sepsis-related organ dysfunction, found no significant advantage for combination therapy. Also, mortality rates were similar at 28 days and at 90 days in both groups. Considering some opposite observations coming from other recent non-randomized studies, we aimed to discuss the raisons of these conflicting findings on antimicrobials combination in patients with severe sepsis and septic shock.

Echocardiography and pulse contour analysis to assess cardiac output in trauma patients.

BACKGROUND: Echocardiography is a valuable technique to assess cardiac output (CO) in trauma patients, but it does not allow a continuous bedside monitoring. Beat-to-beat CO assessment can be obtained by other techniques, including the pulse contour method MostCare. The aim of our study was to compare CO obtained with MostCare (MC-CO) with CO estimated by transthoracic echocardiography (TTE-CO) in trauma patients. METHODS: Forty-nine patients with blunt trauma admitted to an intensive care unit and requiring hemodynamic optimization within 24 hours from admission were studied. TTE-CO and MC-CO were estimated simultaneously at baseline, after a fluid challenge and after the start of vasoactive drug therapy. RESULTS: One hundred sixteen paired CO values were obtained. TTE-CO values ranged from 2.9 to 7.6 L·min(-1), and MC-CO ranged from 2.8 to 8.2 L·min(-1). The correlation between the two methods was 0.94 (95% confidence interval [CI]=0.89 to 0.97; P<0.001). The mean bias was -0.06 L·min(-1) with limits of agreements (LoA) of -0.94 to 0.82 L·min(-1) (lower 95% CI, -1.16 to -0.72; upper 95% CI, 0.60 to 1.04) and a percentage error of 18%. Changes in CO showed a correlation of 0.91 (95% CI=0.87 to 0.95; P<0.001), a mean bias of -0.01 L·min(-1) with LoA of -0.67 to 0.65 L·min(-1) (lower 95% CI, -0.83 to -0.51; upper 95% CI, 0.48 to 0.81). CONCLUSION: CO measured by MostCare showed good agreement with CO obtained by transthoracic echocardiography. Pulse contour analysis can complement echocardiography in evaluating hemodynamics in trauma patients.

When, where and how to initiate hypothermia after adult cardiac arrest.

Therapeutich hypothermia (TH) has been shown to improve neurological outcome and survival after witnessed cardiac arrest (CA) that is due to ventricular fibrillation. Although TH is widely used following witnessed CA as well as all forms of initial rhythm, the mortality rate after CA remains unacceptably high, and additional study is needed to understand when and how to implement hypothermia in the post-resuscitation phase. Experimental studies have emphasized the importance of initiating cooling soon after the return of spontaneous circulation (ROSC) or even during cardiopulmonary resuscitation (CPR). Clinical studies have shown that pre-hospital induction of hypothermia is feasible and has no major adverse events-even when used intra-arrest-and may provide some additional benefits compared to delayed in-hospital cooling. Thus, hypothermia use should not be limited to the Intensive Care Unit but can be initiated in the field/ambulance or in the Emergency Department, then continued after hospital admission- even during specific procedures such as coronary angiography-as part of the global management of CA patients. Various methods (both non-invasive and invasive) are available to achieve and maintain the target temperature; however, only some of these methods-which include cold fluids, ice packs, iced pads and helmet and trans-nasal cooling- are easily deployed in the pre-hospital setting.

Comparison between an uncalibrated pulse contour method and thermodilution technique for cardiac output estimation in septic patients.

BACKGROUND: The purpose of this study was to evaluate the reliability of a new uncalibrated pulse contour method, the MostCare, in determining cardiac output (CO) in septic patients. METHODS: Thirty patients with septic shock admitted to an intensive care unit, receiving a norepinephrine infusion and requiring haemodynamic monitoring with a pulmonary artery catheter, were prospectively enrolled. Thermodilution measurements of CO (ThD-CO) were considered as the 'gold standard'. MostCare was connected to the monitoring system of the radial arterial pressure waveform to obtain a continuous CO calculation (MostCare-CO). ThD-CO and MostCare-CO measurements were recorded at three different haemodynamic states: baseline (T1), after raising mean arterial pressure (MAP) to 90 mm Hg by increasing the norepinephrine infusion (T2), and after returning the MAP to baseline value by decreasing vasopressor therapy (T3). A Bland-Altman and linear regression analyses were performed. RESULTS: A total of 90 paired ThD-CO and MostCare-CO measures were obtained (range 4.1-13.9 litre min(-1) for ThD-CO and 4.5-13.5 litre min(-1) for MostCare-CO). A good correlation between ThD-CO and MostCare-CO was observed (R = 0.93). The mean bias between the two techniques was -0.26 litre min(-1) (sd 0.98 litre min(-1)) and the 95% limits of agreement were -2.22 to 1.70 litre min(-1). The percentage of error was 25%. Pearson's R was 0.94, 0.92, and 0.93 at T1, T2, and T3, respectively. CONCLUSIONS: MostCare-CO and ThD-CO showed a good agreement at each time of the study. The reliability of the MostCare system was not affected by the vascular tone changes produced by a norepinephrine infusion.