Clinical characteristics, respiratory management, and determinants of oxygenation in COVID-19 ARDS: A prospective cohort study.

PURPOSE: To identify determinants of oxygenation over time in patients with COVID-19 acute respiratory distress syndrome (ARDS); and to analyze their characteristics according to Berlin definition categories. MATERIALS AND METHODS: Prospective cohort study including consecutive mechanically ventilated patients admitted between 3/20/2020-10/31/2020 with ARDS. Epidemiological and clinical data on admission; outcomes; ventilation, respiratory mechanics and oxygenation variables were registered on days 1, 3 and 7 for the entire population and for ARDS categories. RESULTS: 1525 patients aged 61 ± 13, 69% male, met ARDS criteria; most frequent comorbidities were obesity, hypertension, diabetes and respiratory disease. On admission, 331(21%), 849(56%) and 345(23%) patients had mild, moderate and severe ARDS; all received lung-protective ventilation (mean tidal volumes between 6.3 and 6.7 mL/kg PBW) and intermediate PEEP levels (10-11 cmH2O). PaO2/FiO2, plateau pressure, static compliance, driving pressure, ventilation ratio, pH and D-dimer >2 mg/L remained significantly different among the ARDS categories over time. In-hospital mortality was, respectively, 55%, 58% and 70% (p < 0.000). Independent predictors of changes of PaO2/FiO2 over time were BMI; preexistent respiratory disease; D-dimer >2 mg/L; day 1-PEEP, and day 1-ventilatory ratio. CONCLUSION: Hypoxemia in patients with COVID-19-related ARDS is associated with comorbidities, deadspace and activated coagulation markers, and disease severity-reflected by the PEEP level required.

Capacidad estructural, recursos humanos tecnológicos y requerimientos de ventilación mecánica en 58 unidades de cuidados intensivos en argentina durante la pandemia por SARS-CoV-2. Estudio SATICOVID-19 / Structural capacity, technological human resources and mechanical ventilation requirements in 58 intensive care units in Argentina during the SARS-CoV-2 pandemic. A SATICOVID-19 Study

Resumen Durante la pandemia por SARS-CoV-2 hubo un marcado requerimiento de camas de cuidados críticos, insumos y profesionales entrenados para asistir a pacientes con insuficiencia respiratoria grave. La Sociedad Argentina de Terapia Intensiva (SATI) diseñó un estudio para caracterizar estos aspectos en las Unidades de Cuidados Intensivos (UCIs). Estudio multicéntrico, de cohorte prospectiva; las UCIs participantes completaron un formulario al final del estudio (31/10/2020) sobre características hospitalarias, número de camas de áreas críticas pre- e intra-pandemia, incorporación de profesionales, insumos y recursos tecnológicos, y carga de trabajo. Participaron 58 UCIs; 28(48%) de Provincia de Buenos Aires, 22(38%) de Ciudad Autónoma de Bue nos Aires, 10(17%) de otras; 31(53%) UCIs pertenecían al sector público; 23(47%) al privado-seguridad social. En 35/58(60%) hospitales las camas de cuidados críticos aumentaron de 902 a 1575(75%); 37% en UCI y 63% principalmente en Unidad Coronaria y Emergencias-shock room. En 41/55(75%) UCIs se incorporó personal: 27(49%) médicos/as (70% intensivistas), 36(65%) enfermeros/as, 28(51%) kinesiólogos/as, 20(36%) personal de limpieza, y 1(2%) otros/as; 96% de las UCIS reportaron disponer de respiradores suficientes, y 95%, insumos y EPP suficientes. De todos los pacientes en ventilación mecánica invasiva, 55% [43-64] presentaron COVID-19. Se requirió oxigenoterapia como soporte no invasivo en 14% [8-24] de los ingresos por COVID-19. Se registró una importante expansión de las áreas críticas operativas, secundariamente al aumento de camas, personal, y adecuada disponibilidad de respiradores e insumos esenciales. La carga de la enfermedad crítica por COVID-19 fue intensa, constituyendo más de la mitad de los pacientes en ventilación mecánica.

Abstract During the SARS-CoV-2 pandemic, there was a marked requirement for critical care beds, supplies and trained professionals to assist patients with severe respiratory failure. The Argentine Society of Intensive Care (SATI) designed a study to characterize these aspects in intensive care units (ICUs). Multicenter, prospective cohort study; the participating ICUs completed a form at the end of the study (31/10/2020) on hospital characteristics, number of beds in pre- and intra-pandemic critical areas, incorporation of professionals, technological resources, and workload. Fifty-eight ICUs participated; 28(48%) were located in Buenos Aires Province, 22(38%) in Buenos Aires Autonomous City and 10 (17%) in other provinces; 31 (53%) of UCIs belonged to the public sector; 23 (47%) to the private-social security. In 35/58 (60%) of the hospitals critical care beds increased from 902 to 1575 (75%), 37% in ICU and 63% mainly in Coronary Care Unit and Emergency-shock room. In 41/55 (75%) UCIs, staff were incorporated: 27(49%) physicians (70% intensivists), 36 (65%) nurses, 28 (51%) respiratory therapists, 20(36%) cleaning staff, and 1(2%) others. A 96% of the ICUS reported having sufficient ventilators and 95% enough sup plies and PPE. Of all patients on invasive mechanical ventilation, 55% [43-64] had COVID-19. Oxygen therapy was required as noninvasive support in 14% [8-24] of COVID-19 admissions. There was a significant expansion of critical operational areas, secondary to the increase in beds, staff, and adequate availability of ventilators and essential supplies. The burden of critical illness from COVID-19 was intense, with more than half of patients on mechanical ventilation.

[Structural capacity, technological human resources and mechanical ventilation requirements in 58 intensive care units in Argentina during the SARS-CoV-2 pandemic. A SATICOVID-19 Study]. / Capacidad estructural, recursos humanos tecnológicos y requerimientos de ventilación mecánica en 58 unidades de cuidados intensivos en Argentina durante la pandemia por SARS-CoV-2. Estudio SATICOVID-19.

During the SARS-CoV-2 pandemic, there was a marked requirement for critical care beds, supplies and trained professionals to assist patients with severe respiratory failure. The Argentine Society of Intensive Care (SATI) designed a study to characterize these aspects in intensive care units (ICUs). Multicenter, prospective cohort study; the participating ICUs completed a form at the end of the study (31/10/2020) on hospital characteristics, number of beds in pre- and intra-pandemic critical areas, incorporation of professionals, technological resources, and workload. Fifty-eight ICUs participated; 28(48%) were located in Buenos Aires Province, 22(38%) in Buenos Aires Autonomous City and 10 (17%) in other provinces; 31 (53%) of UCIs belonged to the public sector; 23 (47%) to the private-social security. In 35/58 (60%) of the hospitals critical care beds increased from 902 to 1575 (75%), 37% in ICU and 63% mainly in Coronary Care Unit and Emergency-shock room. In 41/55 (75%) UCIs, staff were incorporated: 27(49%) physicians (70% intensivists), 36 (65%) nurses, 28 (51%) respiratory therapists, 20(36%) cleaning staff, and 1(2%) others. A 96% of the ICUS reported having sufficient ventilators and 95% enough supplies and PPE. Of all patients on invasive mechanical ventilation, 55% [43-64] had COVID-19. Oxygen therapy was required as noninvasive support in 14% [8-24] of COVID-19 admissions. There was a significant expansion of critical operational areas, secondary to the increase in beds, staff, and adequate availability of ventilators and essential supplies. The burden of critical illness from COVID-19 was intense, with more than half of patients on mechanical ventilation.

Durante la pandemia por SARS-CoV-2 hubo un marcado requerimiento de camas de cuidados críticos, insumos y profesionales entrenados para asistir a pacientes con insuficiencia respiratoria grave. La Sociedad Argentina de Terapia Intensiva (SATI) diseñó un estudio para caracterizar estos aspectos en las Unidades de Cuidados Intensivos (UCIs). Estudio multicéntrico, de cohorte prospectiva; las UCIs participantes completaron un formulario al final del estudio (31/10/2020) sobre características hospitalarias, número de camas de áreas críticas pre- e intra-pandemia, incorporación de profesionales, insumos y recursos tecnológicos, y carga de trabajo. Participaron 58 UCIs; 28(48%) de Provincia de Buenos Aires, 22(38%) de Ciudad Autónoma de Buenos Aires, 10(17%) de otras; 31(53%) UCIs pertenecían al sector público; 23(47%) al privado-seguridad social. En 35/58(60%) hospitales las camas de cuidados críticos aumentaron de 902 a 1575(75%); 37% en UCI y 63% principalmente en Unidad Coronaria y Emergencias-shock room. En 41/55(75%) UCIs se incorporó personal: 27(49%) médicos/as (70% intensivistas), 36(65%) enfermeros/as, 28(51%) kinesiólogos/as, 20(36%) personal de limpieza, y 1(2%) otros/as; 96% de las UCIS reportaron disponer de respiradores suficientes, y 95%, insumos y EPP suficientes. De todos los pacientes en ventilación mecánica invasiva, 55% [43-64] presentaron COVID-19. Se requirió oxigenoterapia como soporte no invasivo en 14% [8-24] de los ingresos por COVID-19. Se registró una importante expansión de las áreas críticas operativas, secundariamente al aumento de camas, personal, y adecuada disponibilidad de respiradores e insumos esenciales. La carga de la enfermedad crítica por COVID-19 fue intensa, constituyendo más de la mitad de los pacientes en ventilación mecánica.

Clinical characteristics and outcomes of invasively ventilated patients with COVID-19 in Argentina (SATICOVID): a prospective, multicentre cohort study.

BACKGROUND: Although COVID-19 has greatly affected many low-income and middle-income countries, detailed information about patients admitted to the intensive care unit (ICU) is still scarce. Our aim was to examine ventilation characteristics and outcomes in invasively ventilated patients with COVID-19 in Argentina, an upper middle-income country. METHODS: In this prospective, multicentre cohort study (SATICOVID), we enrolled patients aged 18 years or older with RT-PCR-confirmed COVID-19 who were on invasive mechanical ventilation and admitted to one of 63 ICUs in Argentina. Patient demographics and clinical, laboratory, and general management variables were collected on day 1 (ICU admission); physiological respiratory and ventilation variables were collected on days 1, 3, and 7. The primary outcome was all-cause in-hospital mortality. All patients were followed until death in hospital or hospital discharge, whichever occurred first. Secondary outcomes were ICU mortality, identification of independent predictors of mortality, duration of invasive mechanical ventilation, and patterns of change in physiological respiratory and mechanical ventilation variables. The study is registered with ClinicalTrials.gov, NCT04611269, and is complete. FINDINGS: Between March 20, 2020, and Oct 31, 2020, we enrolled 1909 invasively ventilated patients with COVID-19, with a median age of 62 years [IQR 52-70]. 1294 (67·8%) were men, hypertension and obesity were the main comorbidities, and 939 (49·2%) patients required vasopressors. Lung-protective ventilation was widely used and median duration of ventilation was 13 days (IQR 7-22). Median tidal volume was 6·1 mL/kg predicted bodyweight (IQR 6·0-7·0) on day 1, and the value increased significantly up to day 7; positive end-expiratory pressure was 10 cm H2O (8-12) on day 1, with a slight but significant decrease to day 7. Ratio of partial pressure of arterial oxygen (PaO2) to fractional inspired oxygen (FiO2) was 160 (IQR 111-218), respiratory system compliance 36 mL/cm H2O (29-44), driving pressure 12 cm H2O (10-14), and FiO2 0·60 (0·45-0·80) on day 1. Acute respiratory distress syndrome developed in 1672 (87·6%) of patients; 1176 (61·6%) received prone positioning. In-hospital mortality was 57·7% (1101/1909 patients) and ICU mortality was 57·0% (1088/1909 patients); 462 (43·8%) patients died of refractory hypoxaemia, frequently overlapping with septic shock (n=174). Cox regression identified age (hazard ratio 1·02 [95% CI 1·01-1·03]), Charlson score (1·16 [1·11-1·23]), endotracheal intubation outside of the ICU (ie, before ICU admission; 1·37 [1·10-1·71]), vasopressor use on day 1 (1·29 [1·07-1·55]), D-dimer concentration (1·02 [1·01-1·03]), PaO2/FiO2 on day 1 (0·998 [0·997-0·999]), arterial pH on day 1 (1·01 [1·00-1·01]), driving pressure on day 1 (1·05 [1·03-1·08]), acute kidney injury (1·66 [1·36-2·03]), and month of admission (1·10 [1·03-1·18]) as independent predictors of mortality. INTERPRETATION: In patients with COVID-19 who required invasive mechanical ventilation, lung-protective ventilation was widely used but mortality was high. Predictors of mortality in our study broadly agreed with those identified in studies of invasively ventilated patients in high-income countries. The sustained burden of COVID-19 on scarce health-care personnel might have contributed to high mortality over the course of our study in Argentina. These data might help to identify points for improvement in the management of patients in middle-income countries and elsewhere. FUNDING: None. TRANSLATION: For the Spanish translation of the Summary see Supplementary Materials section.

Characteristics of resuscitation, and association between use of dynamic tests of fluid responsiveness and outcomes in septic patients: results of a multicenter prospective cohort study in Argentina.

BACKGROUND: Resuscitation of septic patients regarding goals, monitoring aspects and therapy is highly variable. Our aim was to characterize cardiovascular and fluid management of sepsis in Argentina, a low and middle-income country (LMIC). Furthermore, we sought to test whether the utilization of dynamic tests of fluid responsiveness, as a guide for fluid therapy after initial resuscitation in patients with persistent or recurrent hypoperfusion, was associated with decreased mortality. METHODS: Secondary analysis of a national, multicenter prospective cohort study (n = 787) fulfilling Sepsis-3 definitions. Epidemiological characteristics, hemodynamic management data, type of fluids and vasopressors administered, physiological variables denoting hypoperfusion, use of tests of fluid responsiveness, and outcomes, were registered. Independent predictors of mortality were identified with logistic regression analysis. RESULTS: Initially, 584 of 787 patients (74%) had mean arterial pressure (MAP) < 65 mm Hg and/or signs of hypoperfusion and received 30 mL/kg of fluids, mostly normal saline (53%) and Ringer lactate (35%). Vasopressors and/or inotropes were administered in 514 (65%) patients, mainly norepinephrine (100%) and dobutamine (9%); in 22%, vasopressors were administered before ending the fluid load. After this, 413 patients (53%) presented persisting or recurrent hypotension and/or hypoperfusion, which prompted administration of additional fluid, based on: lactate levels (66%), urine output (62%), heart rate (54%), central venous O2 saturation (39%), central venous-arterial PCO2 difference (38%), MAP (31%), dynamic tests of fluid responsiveness (30%), capillary-refill time (28%), mottling (26%), central venous pressure (24%), cardiac index (13%) and/or pulmonary wedge pressure (3%). Independent predictors of mortality were SOFA and Charlson scores, lactate, requirement of mechanical ventilation, and utilization of dynamic tests of fluid responsiveness. CONCLUSIONS: In this prospective observational study assessing the characteristics of resuscitation of septic patients in Argentina, a LMIC, the prevalent use of initial fluid bolus with normal saline and Ringer lactate and the use of norepinephrine as the most frequent vasopressor, reflect current worldwide practices. After initial resuscitation with 30 mL/kg of fluids and vasopressors, 413 patients developed persistent or recurrent hypoperfusion, which required further volume expansion. In this setting, the assessment of fluid responsiveness with dynamic tests to guide fluid resuscitation was independently associated with decreased mortality.

Poor agreement in the calculation of venoarterial PCO2 to arteriovenous O2 content difference ratio using central and mixed venous blood samples in septic patients.

PURPOSE: Central venous minus arterial PCO2 to arterial minus central venous O2 content difference ratio (Pcv-aCO2/Ca-cvO2) has been proposed as a clinical surrogate for respiratory quotient. Our goal was to assess its interchangeability with mixed venous minus arterial PCO2 to arterial minus mixed venous O2 content difference ratio (Pmv-aCO2/Ca-mvO2). MATERIALS AND METHODS: This is a subanalysis of a previously published study. We studied 23 septic patients who had an indwelling Swan-Ganz catheter. The agreement between Pcv-aCO2/Ca-cvO2 and Pmv-aCO2/Ca-mvO2 was evaluated by Bland and Altman analysis. We also performed linear regression analysis with Pmv-aCO2/Ca-mvO2 as the dependent variable. RESULTS: 95% limits of agreement between Pcv-aCO2/Ca-cvO2 and Pmv-aCO2/Ca-mvO2 were 1.48. Pmv-aCO2/Ca-mvO2 was significantly correlated with hemoglobin and lactate (R2 = 0.48 and 0.31, respectively, P < 0.01 for both). CONCLUSIONS: In this study, Pcv-aCO2/Ca-cvO2 and Pmv-aCO2/Ca-mvO2 were not interchangeable. In addition, Pmv-aCO2/Ca-mvO2 is a composite variable, which depends on several determinants. Values of Pcv-aCO2/Ca-cvO2 should be cautiously interpreted in the assessment of critically ill patients.

Predictive Validity of Sepsis-3 Definitions and Sepsis Outcomes in Critically Ill Patients: A Cohort Study in 49 ICUs in Argentina.

OBJECTIVES: The new Sepsis-3 definitions have been scarcely assessed in low- and middle-income countries; besides, regional information of sepsis outcomes is sparse. Our objective was to evaluate Sepsis-3 definition performance in Argentina. DESIGN: Cohort study of 3-month duration beginning on July 1, 2016. SETTINGS: Forty-nine ICUs. PATIENTS: Consecutive patients admitted to the ICU with suspected infection that triggered blood cultures and antibiotic administration. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were classified as having infection, sepsis (infection + change in Sequential Organ Failure Assessment ≥ 2 points), and septic shock (vasopressors + lactate > 2 mmol/L). Patients on vasopressors and lactate less than or equal to 2 mmol/L (cardiovascular dysfunction) were analyzed separately, as those on vasopressors without serum lactate measurement. Systemic inflammatory response syndrome was also recorded. Main outcome was hospital mortality. Of 809 patients, 6% had infection, 29% sepsis, 20% cardiovascular dysfunction, 40% septic shock, and 3% received vasopressors with lactate unmeasured. Hospital mortality was 13%, 20%, 39%, 51%, and 41%, respectively (p = 0.000). Independent predictors of outcome were lactate, Sequential Organ Failure Assessment score, comorbidities, prior duration of symptoms (hr), mechanical ventilation requirement, and infection by highly resistant microorganisms. Area under the receiver operating characteristic curves for mortality for systemic inflammatory response syndrome and Sequential Organ Failure Assessment were 0.53 (0.48-0.55) and 0.74 (0.69-0.77), respectively (p = 0.000). CONCLUSIONS: Increasing severity of Sepsis-3 categories adequately tracks mortality; cardiovascular dysfunction subgroup, not included in Sepsis-3, has distinct characteristics. Sequential Organ Failure Assessment score shows adequate prognosis accuracy-contrary to systemic inflammatory response syndrome. This study supports the predictive validity of Sepsis-3 definitions.

The Effects of Arterial Hypertension and Age on the Sublingual Microcirculation of Healthy Volunteers and Outpatients with Cardiovascular Risk Factors.

OBJECTIVES: To quantitatively assess the effects of age, blood pressure, chronic arterial hypertension, and physical activity on sublingual microcirculation in ambulatory volunteers. METHODS: Sublingual microcirculation was assessed in 61 volunteers with or without chronic arterial hypertension. RESULTS: Volunteers with chronic arterial hypertension had lower TVD all vessels, and TVD small vessels and PVD small vessels than those without this condition (16.0 ± 1.4 vs. 17.2 ± 1.6 mm/mm(2), p < 0.01, 15.1 ± 1.3 vs. 16.1 ± 1.7 mm/mm(2), p < 0.04, and 15.1 ± 1.3 vs. 16.1 ± 1.7 mm/mm(2), p < 0.04, respectively). Mean blood pressure correlated with TVD all vessels (r = -0.34, p < 0.01), TVD small vessels (r = -0.31, p < 0.02), and PVD small vessels (r = -0.27, p < 0.04) but not with other microvascular variables. Age was not correlated with any microcirculatory variables. Physical activity correlated with TVDall vessels and RBCV small vessels (r = 0.30, p < 0.02 and r = -0.47, p < 0.001, respectively). Chronic arterial hypertension was the only independent determinant of PVD small vessels . CONCLUSIONS: Preexistent chronic arterial hypertension was associated with lower vascular densities. In contrast, age showed no effect on sublingual microcirculation.

Effects of norepinephrine on tissue perfusion in a sheep model of intra-abdominal hypertension.

BACKGROUND: The aim of the study was to describe the effects of intra-abdominal hypertension (IAH) on regional and microcirculatory intestinal blood flow, renal blood flow, and urine output, as well as their response to increases in blood pressure induced by norepinephrine. METHODS: This was a pilot, controlled study, performed in an animal research laboratory. Twenty-four anesthetized and mechanically ventilated sheep were studied. We measured systemic hemodynamics, superior mesenteric and renal blood flow, villi microcirculation, intramucosal-arterial PCO2, urine output, and intra-abdominal pressure. IAH (20 mm Hg) was generated by intraperitoneal instillation of warmed saline. After 1 h of IAH, sheep were randomized to IAH control (n = 8) or IAH norepinephrine (n = 8) groups, for 1 h. In this last group, mean arterial pressure was increased about 20 mm Hg with norepinephrine. A sham group (n = 8) was also studied. Fluids were administered to prevent decreases in cardiac output. Differences between groups were analyzed with two-way repeated measures of analysis of variance (ANOVA). RESULTS: After 2 h of IAH, abdominal perfusion pressure decreased in IAH control group compared to IAH norepinephrine and sham groups (49 ± 11, 73 ± 11, and 86 ± 15 mm Hg, P < 0.0001). There were no differences in superior mesenteric artery blood flow, intramucosal-arterial PCO2, and villi microcirculation among groups. Renal blood flow (49 ± 30, 32 ± 24, and 102 ± 45 mL.min(-1).kg(-1), P < 0.0001) and urinary output (0.3 ± 0.1, 0.2 ± 0.2, and 1.0 ± 0.6 mL.h(-1).kg(-1), P < 0.0001) were decreased in IAH control and IAH norepinephrine groups, compared to the sham group. CONCLUSIONS: In this experimental model of IAH, the gut and the kidney had contrasting responses: While intestinal blood flow and villi microcirculation remained unchanged, renal perfusion and urine output were severely compromised.

What is microcirculatory shock?

PURPOSE OF REVIEW: Microcirculatory shock is a condition defined by the presence of tissue hypoperfusion despite the normalization of systemic and regional blood flow. In this article, we discuss the characteristics of the microcirculation in septic shock, the main form of microcirculatory shock, along with its interaction with systemic hemodynamics, and the response to different therapies. RECENT FINDINGS: In septic shock, microcirculatory abnormalities are common, and more severe in nonsurvivors. In addition, the microcirculation shows a behavior that is frequently dissociated from that of systemic hemodynamics. Therefore, microcirculatory alterations may persist despite correction of systemic hemodynamic variables. Sublingual and intestinal microcirculation might also display divergent behaviors. Moreover, microvascular alterations may improve in response to hemodynamic resuscitation, but the response might depend on the underlying microcirculatory alterations. Particularly, the response to fluids seems to be related to both its basal state and the magnitude of the increase in cardiac output. SUMMARY: The optimal treatment of microcirculatory shock might require monitoring and therapeutic goals targeted on the microcirculation, more than in systemic variables. The clinical benefits of this approach should be demonstrated in clinical trials.

Systemic and microcirculatory effects of dobutamine in patients with septic shock.

PURPOSE: The aim of this study was to characterize the cardiovascular responses to dobutamine and their predictors. Our hypotheses were that dobutamine mainly produces tachycardia and vasodilation and fails to improve the microcirculation of patients with septic shock. MATERIALS AND METHODS: Systemic hemodynamics and sublingual microcirculation were evaluated with dobutamine (0, 2.5, 5.0, and 10.0 µg kg(-1) min(-1)) in 23 patients with septic shock. RESULTS: Dobutamine increased heart rate, cardiac index, and stroke volume index (SVI). Mean blood pressure was unchanged, and systemic vascular resistance decreased. Individual responses were heterogeneous. Stroke volume index increased in 52% of the patients. These patients showed lower changes in mean blood pressure (3 ± 16 mm Hg vs -10 ± 6 mm Hg, P < .05) and higher increases in cardiac index (1.47 ± 0.93 L m(-1) m(-2) vs 0.20 ± 0.5 L m(-1) m(-2)) than did nonresponders. Changes in SVI significantly correlated with echocardiographic left ventricular ejection fraction (r = 0.55). In the whole group, perfused capillary density remained unchanged (14.0 ± 4.3 mm/mm(2) vs 14.8 ± 3.7 mm/mm(2)), but improved if basal values were 12 mm/mm(2) or less (9.1 ± 4.3 mm/mm(2) vs 12.5 ± 4.8 mm/mm(2)). CONCLUSIONS: Dobutamine produced variable hemodynamic effects. Systolic dysfunction was the only variable associated with increases in SVI. Finally, dobutamine only improved sublingual microcirculation when severe alterations were found at baseline.

Comparison of different methods for the calculation of the microvascular flow index.

The microvascular flow index (MFI) is commonly used to semiquantitatively characterize the velocity of microcirculatory perfusion as absent (0), intermittent (1), sluggish (2), or normal (3). There are three approaches to compute MFI: (1) the average of the predominant flow in each of the four quadrants (MFI(by quadrants)), (2) the direct assessment during the bedside video acquisition (MFI(point of care)), and (3) the mean value of the MFIs determined in each individual vessel (MFI(vessel by vessel)). We hypothesized that the agreement between the MFIs is poor and that the MFI(vessel by vessel) better reflects the microvascular perfusion. For this purpose, we analyzed 100 videos from septic patients. In 25 of them, red blood cell (RBC) velocity was also measured. There were wide 95% limits of agreement between MFI(by quadrants) and MFI(point of care) (1.46), between MFI(by quadrants) and MFI(vessel by vessel) (2.85), and between MFI(by point of care) and MFI(vessel by vessel) (2.56). The MFIs significantly correlated with the RBC velocity and with the fraction of perfused small vessels, but MFI(vessel by vessel) showed the best R(2). Although the different methods for the calculation of MFI reflect microvascular perfusion, they are not interchangeable and MFI(vessel by vessel) might be better.

The microcirculation as a therapeutic target in the treatment of sepsis and shock.

Largely ignored throughout the history of clinical medicine, the microcirculation has recently been recognized at the bedside as the center of several pathophysiological processes. Normal microcirculatory function is critical for adequate tissue oxygenation and organ function, but it has a poorly understood and highly heterogeneous structure that is related to the diversity of functions that it accomplishes. The most important function of the microcirculation is the regulation and distribution of oxygen carrying red blood cells within the different organs. The determinants of oxygen delivery, blood flow regulation, tissue oxygen tension, and mitochondrial well-being are not fully understood; however, it is clear that insight into the function of the microcirculation is key in this respect. In fact, it is clear that the origin of circulatory failure in critical illness unresponsive to therapy is not represented in systemic hemodynamic variables but rather in the dysfunction of the microcirculation. The introduction of bedside techniques into clinical practice that allow the evaluation of the microcirculation has opened up a new field of functional hemodynamic monitoring, identified the microcirculatory failure as the most sensitive indicator of circulatory failure associated with adverse outcome, and has provided the promise of identifying new therapeutic targets. Clinical research has identified various conventional and new therapeutic approaches that are successful in modifying the microcirculation. Current research must determine whether some of these approaches are successful in improving the outcome of critically ill patients by recruiting the microcirculation.

Comparison of 6% hydroxyethyl starch 130/0.4 and saline solution for resuscitation of the microcirculation during the early goal-directed therapy of septic patients.

PURPOSE: The aim of this study was to show that 6% hydroxyethyl starch (HES) 130/0.4 achieves a better resuscitation of the microcirculation than normal saline solution (SS), during early goal-directed therapy (EGDT) in septic patients. MATERIALS AND METHODS: Patients with severe sepsis were randomized for EGDT with 6% HES 130/0.4 (n = 9) or SS (n = 11). Sublingual microcirculation was evaluated by sidestream dark field imaging 24 hours after the beginning of EGDT. RESULTS: On admission, there were no differences in Sequential Organ Failure Assessment score, mean arterial pressure, lactate, or central venous oxygen saturation. After 24 hours, no difference arose in those parameters. Sublingual capillary density was similar in both groups (21 ± 8 versus 20 ± 3 vessels/mm(2)); but capillary microvascular flow index, percent of perfused capillaries, and perfused capillary density were higher in 6% HES 130/0.4 (2.5 ± 0.5 versus 1.6 ± 0.7, 84 ± 15 versus 53 ± 26%, and 19 ± 6 versus 11 ± 5 vessels/mm(2), respectively, P < .005). CONCLUSIONS: Fluid resuscitation with 6% HES 130/0.4 may have advantages over SS to improve sublingual microcirculation. A greater number of patients would be necessary to confirm these findings.

Effects of recruitment manoeuvres on haemodynamics, oxygen exchange and oxygen delivery in patients with acute lung injury and acute respiratory distress syndrome.

OBJECTIVE: To evaluate the impact of a recruitment manoeuvre (RM) on haemodynamics, gas exchange, and oxygen transport in patients with acute lung injury (ALI) an acute respiratory distress syndrome (ARDS) under mechanical ventilation. DESIGN, SETTING AND PARTICIPANTS: Prospective interventional study in the intensive care unit of a teaching hospital in Buenos Aires, Argentina. The study was carried out between June 2002 and March 2003. Eleven consecutive patients with ALI and ARDS who required an RM were included. Haemodynamic measurements and blood samples were taken before and during the RM, and at 2 and 30 minutes after the RM. INTERVENTION: After baseline measurements, positive end-expiratory pressure (PEEP) was set at 40cmH(2)O for 45 seconds. MAIN OUTCOME MEASURES: Systemic haemodynamics, oxygen exchange and oxygen delivery. RESULTS: Mean PEEP before the RM was 14 (SD, 3) cmH(2)O, and was maintained after the RM. The RM did not modify the arterial partial pressure of oxygen (PaO(2)) but did induce small but significant changes in the mean arterial partial pressure of carbon dioxide (Pa-ETCO(2)) and arterial minus end-tidal PCO(2) gradient (PaCO(2)) at 2 minutes and 30 minutes after the RM (P<0.05). The mean cardiac index dropped from 3.08 (SD, 0.84) to 2.37 (SD, 0.75) L/min/m(2) (P<0.001) during the RM and then returned to baseline values. Mean systolic blood pressure also fell transitorily during the RM, from 131 (SD, 15) to 104 (SD, 25) mmHg, but diastolic and mean arterial pressures remained unchanged. Oxygen consumption and the arterial mixed venous oxygen content gradient increased after the RM (P<0.05). CONCLUSION: In our small series of patients with ALI/ARDS ventilated with high levels of PEEP, the RM failed to improve oxygen exchange and induced deleterious effects on haemodynamics.

Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study.

INTRODUCTION: Our goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation. METHODS: Twenty septic shock patients were prospectively studied in two teaching intensive care units. The patients were mechanically ventilated and required norepinephrine to maintain a mean arterial pressure (MAP) of 65 mmHg. We measured systemic hemodynamics, oxygen transport and consumption (DO2 and VO2), lactate, albumin-corrected anion gap, and gastric intramucosal-arterial PCO2 difference (DeltaPCO2). Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. After basal measurements at a MAP of 65 mmHg, norepinephrine was titrated to reach a MAP of 75 mmHg, and then to 85 mmHg. Data were analyzed using repeated measurements ANOVA and Dunnett test. Linear trends between the different variables and increasing levels of MAP were calculated. RESULTS: Increasing doses of norepinephrine reached the target values of MAP. The cardiac index, pulmonary pressures, systemic vascular resistance, and left and right ventricular stroke work indexes increased as norepinephrine infusion was augmented. Heart rate, DO2 and VO2, lactate, albumin-corrected anion gap, and DeltaPCO2 remained unchanged. There were no changes in sublingual capillary microvascular flow index (2.1 +/- 0.7, 2.2 +/- 0.7, 2.0 +/- 0.8) and the percent of perfused capillaries (72 +/- 26, 71 +/- 27, 67 +/- 32%) for MAP values of 65, 75, and 85 mmHg, respectively. There was, however, a trend to decreased capillary perfused density (18 +/- 10,17 +/- 10,14 +/- 2 vessels/mm2, respectively, ANOVA P = 0.09, linear trend P = 0.045). In addition, the changes of perfused capillary density at increasing MAP were inversely correlated with the basal perfused capillary density (R2 = 0.95, P < 0.0001). CONCLUSIONS: Patients with septic shock showed severe sublingual microcirculatory alterations that failed to improve with the increases in MAP with norepinephrine. Nevertheless, there was a considerable interindividual variation. Our results suggest that the increase in MAP above 65 mmHg is not an adequate approach to improve microcirculatory perfusion and might be harmful in some patients.