The Effects of Dobutamine in Septic Shock: An Updated Narrative Review of Clinical and Experimental Studies.

The key objective in the hemodynamic treatment of septic shock is the optimization of tissue perfusion and oxygenation. This is usually achieved by the utilization of fluids, vasopressors, and inotropes. Dobutamine is the inotrope most commonly recommended and used for this purpose. Despite the fact that dobutamine was introduced almost half a century ago in the treatment of septic shock, and there is widespread use of the drug, several aspects of its pharmacodynamics remain poorly understood. In normal subjects, dobutamine increases contractility and lacks a direct effect on vascular tone. This results in augmented cardiac output and blood pressure, with reflex reduction in systemic vascular resistance. In septic shock, some experimental and clinical research suggest beneficial effects on systemic and regional perfusion. Nevertheless, other studies found heterogeneous and unpredictable effects with frequent side effects. In this narrative review, we discuss the pharmacodynamic characteristics of dobutamine and its physiologic actions in different settings, with special reference to septic shock. We discuss studies showing that dobutamine frequently induces tachycardia and vasodilation, without positive actions on contractility. Since untoward effects are often found and therapeutic benefits are occasional, its profile of efficacy and safety seems low. Therefore, we recommend that the use of dobutamine in septic shock should be cautious. Before a final decision about its prescription, efficacy, and tolerance should be evaluated throughout a short period with narrow monitoring of its wanted and side effects.

Microcirculatory effects of rewarming in experimental hemorrhagic shock.

BACKGROUND: Rewarming is a recommended therapy during the resuscitation of hypothermic patients with hemorrhagic shock. In experimental models, however, it increases inflammatory response and mortality. Although microcirculation is potential target of inflammation, the microvascular effects of rewarming during the resuscitation of hemorrhagic shock have not been studied. Our goal was to assess the systemic and microcirculatory effects of an increase in core temperature (T°) during the retransfusion of hemorrhagic shock in sheep. Our hypothesis was that rewarming could hamper microcirculation. METHODS: In anesthetized and mechanically ventilated sheep, we measured systemic, intestinal, and renal hemodynamics and oxygen transport. O2 consumption (VO2) and respiratory quotient were measured by indirect calorimetry. Cortical renal, intestinal villi and sublingual microcirculation were assessed by IDF-videomicroscopy. After basal measurements, hemorrhagic shock was induced and T° was reduced to ~33 °C. After 1 h of shock and hypothermia, blood was retransfused and Ringer lactate solution was administered to prevent arterial hypotension. In the control group (n = 12), T° was not modified, while in the intervention (rewarming) group, it was elevated ~3 °C. Measurements were repeated after 1 h. RESULTS: During shock, both groups showed similar systemic and microvascular derangements. After retransfusion, VO2 remained decreased compared to baseline in both groups, but was lower in the control compared to the rewarming group. Perfused vascular density has a similar behavior in both groups. Compared to baseline, it remained reduced in peritubular (control vs. rewarming group, 13.8 [8.7-17.5] vs. 15.7 [10.1-17.9] mm/mm2, PNS) and villi capillaries (14.7 [13.6-16.8] vs. 16.3 [14.2-16.9] mm/mm2, PNS), and normalized in sublingual mucosa (19.1 [16.0-20.3] vs. 16.6 [14.7-17.2] mm/mm2, PNS). CONCLUSIONS: This is the first experimental study assessing the effect of rewarming on systemic, regional, and microcirculatory perfusion in hypothermic hemorrhagic shock. We found that a 3 °C increase in T° neither improved nor impaired the microvascular alterations that persisted after retransfusion. In addition, sublingual mucosa was less susceptible to reperfusion injury than villi and renal microcirculation.

Venous Minus Arterial Carbon Dioxide Gradients in the Monitoring of Tissue Perfusion and Oxygenation: A Narrative Review.

According to Fick's principle, the total uptake of (or release of) a substance by tissues is the product of blood flow and the difference between the arterial and the venous concentration of the substance. Therefore, the mixed or central venous minus arterial CO2 content difference depends on cardiac output (CO). Assuming a linear relationship between CO2 content and partial pressure, central or mixed venous minus arterial PCO2 differences (Pcv-aCO2 and Pmv-aCO2) are directly related to CO. Nevertheless, this relationship is affected by alterations in the CO2Hb dissociation curve induced by metabolic acidosis, hemodilution, the Haldane effect, and changes in CO2 production (VCO2). In addition, Pcv-aCO2 and Pmv-aCO2 are not interchangeable. Despite these confounders, CO is a main determinant of Pcv-aCO2. Since in a study performed in septic shock patients, Pmv-aCO2 was correlated with changes in sublingual microcirculation but not with those in CO, it has been proposed as a monitor for microcirculation. The respiratory quotient (RQ)-RQ = VCO2/O2 consumption-sharply increases in anaerobic situations induced by exercise or critical reductions in O2 transport. This results from anaerobic VCO2 secondary to bicarbonate buffering of anaerobically generated protons. The measurement of RQ requires expired gas analysis by a metabolic cart, which is not usually available. Thus, some studies have suggested that the ratio of Pcv-aCO2 to arterial minus central venous O2 content (Pcv-aCO2/Ca-cvO2) might be a surrogate for RQ and tissue oxygenation. In this review, we analyze the physiologic determinants of Pcv-aCO2 and Pcv-aCO2/Ca-cvO2 and their potential usefulness and limitations for the monitoring of critically ill patients. We discuss compelling evidence showing that they are misleading surrogates for tissue perfusion and oxygenation, mainly because they are systemic variables that fail to track regional changes. In addition, they are strongly dependent on changes in the CO2Hb dissociation curve, regardless of changes in systemic and microvascular perfusion and oxygenation.

Assessment of the peripheral microcirculation in patients with and without shock: a pilot study on different methods.

Microvascular dysfunction has been associated with adverse outcomes in critically ill patients, and the current concept of hemodynamic incoherence has gained attention. Our objective was to perform a comprehensive analysis of microcirculatory perfusion parameters and to investigate the best variables that could discriminate patients with and without circulatory shock during early intensive care unit (ICU) admission. This prospective observational study comprised a sample of 40 adult patients with and without circulatory shock (n = 20, each) admitted to the ICU within 24 h. Peripheral clinical [capillary refill time (CRT), peripheral perfusion index (PPI), skin-temperature gradient (Tskin-diff)] and laboratory [arterial lactate and base excess (BE)] perfusion parameters, in addition to near-infrared spectroscopy (NIRS)-derived variables were simultaneously assessed. While lactate, BE, CRT, PPI and Tskin-diff did not differ significantly between the groups, shock patients had lower baseline tissue oxygen saturation (StO2) [81 (76-83) % vs. 86 (76-90) %, p = 0.044], lower StO2min [50 (47-57) % vs. 55 (53-65)  %, p = 0.038] and lower StO2max [87 (80-92) % vs. 93 (90-95) %, p = 0.017] than patients without shock. Additionally, dynamic NIRS variables [recovery time (r = 0.56, p = 0.010), descending slope (r = - 0.44, p = 0.05) and ascending slope (r = - 0.54, p = 0.014)] and not static variable [baseline StO2 (r = - 0.24, p = 0.28)] exhibited a significant correlation with the administered dose of norepinephrine. In our study with critically ill patients assessed within the first twenty-four hours of ICU admission, among the perfusion parameters, only NIRS-derived parameters could discriminate patients with and without shock.

Health inequities in the diagnosis and outcome of sepsis in Argentina: a prospective cohort study.

BACKGROUND: Socioeconomic variables impact health outcomes but have rarely been evaluated in critical illness. Low- and middle-income countries bear the highest burden of sepsis and also have significant health inequities. In Argentina, public hospitals serve the poorest segment of the population, while private institutions serve patients with health coverage. Our objective was to analyze differences in mortality between public and private hospitals, using Sepsis-3 definitions. METHODS: This is a multicenter, prospective cohort study including patients with sepsis admitted to 49 Argentine ICUs lasting 3 months, beginning on July 1, 2016. Epidemiological, clinical, and socioeconomic status variables and hospital characteristics were compared between patients admitted to both types of institutions. RESULTS: Of the 809 patients included, 367 (45%) and 442 (55%) were admitted to public and private hospitals, respectively. Those in public institutions were younger (56 ± 18 vs. 64 ± 18; p < 0.01), with more comorbidities (Charlson score 2 [0-4] vs. 1 [0-3]; p < 0.01), fewer education years (7 [7-12] vs. 12 [10-16]; p < 0.01), more frequently unemployed/informally employed (30% vs. 7%; p < 0.01), had similar previous self-rated health status (70 [50-90] vs. 70 [50-90] points; p = 0.30), longer pre-admission symptoms (48 [24-96] vs. 24 [12-48] h; p < 0.01), had been previously evaluated more frequently in any healthcare venue (28 vs. 20%; p < 0.01), and had higher APACHE II, SOFA, lactate levels, and mechanical ventilation utilization. ICU admission as septic shock was more frequent in patients admitted to public hospitals (47 vs. 35%; p < 0.01), as were infections caused by multiresistant microorganisms. Sepsis management in the ICU showed no differences. Twenty-eight-day mortality was higher in public hospitals (42% vs. 24%; p < 0.01) as was hospital mortality (47% vs. 30%; p < 0.01). Admission to a public hospital was an independent predictor of mortality together with comorbidities, lactate, SOFA, and mechanical ventilation; in an alternative prediction model, it acted as a correlate of pre-hospital symptom duration and infections caused by multiresistant microorganisms. CONCLUSIONS: Patients in public hospitals belonged to a socially disadvantaged group and were sicker at admission, had septic shock more frequently, and had higher mortality. Unawareness of disease severity and delays in the health system might be associated with late admission. This marked difference in outcome between patients served by public and private institutions constitutes a state of health inequity.

Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial.

Importance: Abnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of peripheral perfusion as a target during resuscitation in early septic shock has not been established. Objective: To determine if a peripheral perfusion-targeted resuscitation during early septic shock in adults is more effective than a lactate level-targeted resuscitation for reducing mortality. Design, Setting, and Participants: Multicenter, randomized trial conducted at 28 intensive care units in 5 countries. Four-hundred twenty-four patients with septic shock were included between March 2017 and March 2018. The last date of follow-up was June 12, 2018. Interventions: Patients were randomized to a step-by-step resuscitation protocol aimed at either normalizing capillary refill time (n = 212) or normalizing or decreasing lactate levels at rates greater than 20% per 2 hours (n = 212), during an 8-hour intervention period. Main Outcomes and Measures: The primary outcome was all-cause mortality at 28 days. Secondary outcomes were organ dysfunction at 72 hours after randomization, as assessed by Sequential Organ Failure Assessment (SOFA) score (range, 0 [best] to 24 [worst]); death within 90 days; mechanical ventilation-, renal replacement therapy-, and vasopressor-free days within 28 days; intensive care unit and hospital length of stay. Results: Among 424 patients randomized (mean age, 63 years; 226 [53%] women), 416 (98%) completed the trial. By day 28, 74 patients (34.9%) in the peripheral perfusion group and 92 patients (43.4%) in the lactate group had died (hazard ratio, 0.75 [95% CI, 0.55 to 1.02]; P = .06; risk difference, -8.5% [95% CI, -18.2% to 1.2%]). Peripheral perfusion-targeted resuscitation was associated with less organ dysfunction at 72 hours (mean SOFA score, 5.6 [SD, 4.3] vs 6.6 [SD, 4.7]; mean difference, -1.00 [95% CI, -1.97 to -0.02]; P = .045). There were no significant differences in the other 6 secondary outcomes. No protocol-related serious adverse reactions were confirmed. Conclusions and Relevance: Among patients with septic shock, a resuscitation strategy targeting normalization of capillary refill time, compared with a strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT03078712.

Sublingual microcirculatory alterations in cirrhotic patients.

OBJECTIVE: To assess sublingual microcirculation in cirrhotic patients and its relationship to spider angiomas, complications, and outcome. METHODS: Thirty-one cirrhotic patients were prospectively compared to 31 matched controls. Sublingual microcirculation was evaluated by videomicroscopy. We specifically looked for capillaries with increased RBCV, which was defined as a velocity higher than the percentile 100th of controls. RESULTS: Compared to controls, cirrhotic patients showed decreased total and PVD (14.4 ± 2.2 vs 16.0 ± 1.3 and 14.1 ± 2.3 vs 15.9 ± 1.6 mm/mm2 , respectively, P < .001 for both) and increased HFI (0.64 ± 0.39 vs 0.36 ± 0.21, P = .001). They also exhibited high RBCV in 2% of the microvessels (P < .0001). Patients with MELD score ≥10 had higher RBCV than patients with score <10 (1414 ± 290 vs 1206 ± 239 µm/s, P < .05). Patients with spider angiomas showed lower vascular densities. Microcirculation did not differ between survivors and nonsurvivors. CONCLUSIONS: Cirrhosis is associated with microcirculatory alterations that can be easily monitored in the sublingual mucosa. Alterations included decreased density and PPV and hyperdynamic microvessels. The most striking finding, however, was the microvascular heterogeneity. Patients with spider angiomas had more severe alterations. Larger studies should clarify the relationship between microcirculatory abnormalities and outcome.

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.

Monitoring peripheral perfusion and microcirculation.

PURPOSE OF REVIEW: Microcirculatory alterations play a major role in the pathogenesis of shock. Monitoring tissue perfusion might be a relevant goal for shock resuscitation. The goal of this review was to revise the evidence supporting the monitoring of peripheral perfusion and microcirculation as goals of resuscitation. For this purpose, we mainly focused on skin perfusion and sublingual microcirculation. RECENT FINDINGS: Although there are controversies about the reproducibility of capillary refill time in monitoring peripheral perfusion, it is a sound physiological variable and suitable for the ICU settings. In addition, observational studies showed its strong ability to predict outcome. Moreover, a preliminary study suggested that it might be a valuable goal for resuscitation. These results should be confirmed by the ongoing ANDROMEDA-SHOCK randomized controlled trial. On the other hand, the monitoring of sublingual microcirculation might also provide relevant physiological and prognostic information. On the contrary, methodological drawbacks mainly related to video assessment hamper its clinical implementation at the present time. SUMMARY: Measurements of peripheral perfusion might be useful as goal of resuscitation. The results of the ANDROMEDA-SHOCK will clarify the role of skin perfusion as a guide for the treatment of shock. In contrast, the assessment of sublingual microcirculation mainly remains as a research tool.

The practice of intensive care in Latin America: a survey of academic intensivists.

BACKGROUND: Intensive care medicine is a relatively young discipline that has rapidly grown into a full-fledged medical subspecialty. Intensivists are responsible for managing an ever-increasing number of patients with complex, life-threatening diseases. Several factors may influence their performance, including age, training, experience, workload, and socioeconomic context. The aim of this study was to examine individual- and work-related aspects of the Latin American intensivist workforce, mainly with academic appointments, which might influence the quality of care provided. In consequence, we conducted a cross-sectional study of intensivists at public and private academic and nonacademic Latin American intensive care units (ICUs) through a web-based electronic survey submitted by email. Questions about personal aspects, work-related topics, and general clinical workflow were incorporated. RESULTS: Our study comprised 735 survey respondents (53% return rate) with the following country-specific breakdown: Brazil (29%); Argentina (19%); Chile (17%); Uruguay (12%); Ecuador (9%); Mexico (7%); Colombia (5%); and Bolivia, Peru, Guatemala, and Paraguay combined (2%). Latin American intensivists were predominantly male (68%) young adults (median age, 40 [IQR, 35-48] years) with a median clinical ICU experience of 10 (IQR, 5-20) years. The median weekly workload was 60 (IQR, 47-70) h. ICU formal training was between 2 and 4 years. Only 63% of academic ICUs performed multidisciplinary rounds. Most intensivists (85%) reported adequate conditions to manage patients with septic shock in their units. Unsatisfactory conditions were attributed to insufficient technology (11%), laboratory support (5%), imaging resources (5%), and drug shortages (5%). Seventy percent of intensivists participated in research, and 54% read scientific studies regularly, whereas 32% read no more than one scientific study per month. Research grants and pharmaceutical sponsorship are unusual funding sources in Latin America. Although Latin American intensivists are mostly unsatisfied with their income (81%), only a minority (27%) considered changing to another specialty before retirement. CONCLUSIONS: Latin American intensivists constitute a predominantly young adult workforce, mostly formally trained, have a high workload, and most are interested in research. They are under important limitations owing to resource constraints and overt dissatisfaction. Latin America may be representative of other world areas with similar challenges for intensivists. Specific initiatives aimed at addressing these situations need to be devised to improve the quality of critical care delivery in Latin America.

Relationship of at Admission Lactate, Unmeasured Anions, and Chloride to the Outcome of Critically Ill Patients.

OBJECTIVES: To investigate the association between the concentration of the causative anions responsible for the main types of metabolic acidosis and the outcome. DESIGN: Prospective observational study. SETTING: Teaching ICU. PATIENTS: All patients admitted from January 2006 to December 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four thousand nine hundred one patients were admitted throughout the study period; 1,609 met criteria for metabolic acidosis and 145 had normal acid-base values. The association between at admission lactate, unmeasured anions, and chloride concentration with outcome was assessed by multivariate analysis in the whole cohort and in patients with metabolic acidosis. We also compared the mortality of patients with lactic, unmeasured anions, and hyperchloremic metabolic acidosis with that of patients without acid-base disorders. In the whole population, increased lactate and unmeasured anions were independently associated with increased mortality, even after adjusting for potential confounders (odds ratio [95% CI], 1.14 (1.08-1.20); p < 0.0001 and 1.04 (1.02-1.06); p < 0.0001, respectively). In patients with metabolic acidosis, the results were similar. Patients with lactic and unmeasured anions acidosis, but not those with hyperchloremic acidosis, had an increased mortality compared to patients without alterations (17.7%, 12.7%, 4.9%, and 5.8%, respectively; p < 0.05). CONCLUSIONS: In this large cohort of critically ill patients, increased concentrations of lactate and unmeasured anions, but not chloride, were associated with increased mortality. In addition, increased unmeasured anions were the leading cause of metabolic acidosis.

Organizational Issues, Structure, and Processes of Care in 257 ICUs in Latin America: A Study From the Latin America Intensive Care Network.

OBJECTIVE: Latin America bears an important burden of critical care disease, yet the information about it is scarce. Our objective was to describe structure, organization, processes of care, and research activities in Latin-American ICUs. DESIGN: Web-based survey submitted to ICU directors. SETTINGS: ICUs located in nine Latin-American countries. SUBJECTS: Individual ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred fifty-seven of 498 (52%) of submitted surveys responded: 51% from Brazil, 17% Chile, 13% Argentina, 6% Ecuador, 5% Uruguay, 3% Colombia, and 5% between Mexico, Peru, and Paraguay. Seventy-nine percent of participating hospitals had less than 500 beds; most were public (59%) and academic (66%). ICUs were mainly medical-surgical (75%); number of beds was evenly distributed in the entire cohort; 77% had 24/7 intensivists; 46% had a physician-to-patient ratio between 1:4 and 7; and 69% had a nurse-to-patient ratio of 1 ≥ 2.1. The 24/7 presence of other specialists was deficient. Protocols in use averaged 9 ± 3. Brazil (vs the rest) had larger hospitals and ICUs and more quality, surveillance, and prevention committees, but fewer 24/7 intensivists and poorer nurse-to-patient ratio. Although standard monitoring, laboratory, and imaging practices were almost universal, more complex measurements and treatments and portable equipment were scarce after standard working hours, and in public hospitals. Mortality was 17.8%, without differences between countries. CONCLUSIONS: This multinational study shows major concerns in the delivery of critical care across Latin America, particularly in human resources. Technology was suboptimal, especially in public hospitals. A 24/7 availability of supporting specialists and of key procedures was inadequate. Mortality was high in comparison to high-income countries.

Mildly elevated lactate levels are associated with microcirculatory flow abnormalities and increased mortality: a microSOAP post hoc analysis.

BACKGROUND: Mildly elevated lactate levels (i.e., 1-2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients. One of several possible underlying mechanisms, microcirculatory dysfunction, can be assessed at the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the association between relative hyperlactatemia, microcirculatory flow, and outcome. METHODS: This study was a predefined subanalysis of a multicenter international point prevalence study on microcirculatory flow abnormalities, the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Microcirculatory flow abnormalities were assessed with sidestream dark-field imaging. Abnormal microcirculatory flow was defined as a microvascular flow index (MFI) < 2.6. MFI is a semiquantitative score ranging from 0 (no flow) to 3 (continuous flow). Associations between microcirculatory flow abnormalities, single-spot lactate measurements, and outcome were analyzed. RESULTS: In 338 of 501 patients, lactate levels were available. For this substudy, all 257 patients with lactate levels ≤ 2 mmol/L (median [IQR] 1.04 [0.80-1.40] mmol/L) were included. Crude ICU mortality increased with each lactate quartile. In a multivariable analysis, a lactate level > 1.5 mmol/L was independently associated with a MFI < 2.6 (OR 2.5, 95% CI 1.1-5.7, P = 0.027). CONCLUSIONS: In a heterogeneous ICU population, a single-spot mildly elevated lactate level (even within the reference range) was independently associated with increased mortality and microvascular flow abnormalities. In vivo microscopy of the microcirculation may be helpful in discriminating between flow- and non-flow-related causes of mildly elevated lactate levels. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01179243 . Registered on August 3, 2010.

[Acute respiratory distress syndrome]. / Síndrome de distrés respiratorio agudo.

Acute respiratory distress syndrome (ARDS) is an acute respiratory failure produced by an inflammatory edema secondary to increased lung capillary permeability. This causes alveolar flooding and subsequently deep hypoxemia, with intrapulmonary shunt as its most important underlying mechanism. Characteristically, this alteration is unresponsive to high FIO2 and only reverses with end-expiratory positive pressure (PEEP). Pulmonary infiltrates on CXR and CT are the hallmark, together with decreased lung compliance. ARDS always occurs within a week of exposition to a precipitating factor; most frequently pneumonia, shock, aspiration of gastric contents, sepsis, and trauma. In CT scan, the disease is frequently inhomogeneous, with gravitational infiltrates coexisting with normal-density areas and also with hyperaerated parenchyma. Mortality is high (30-60%) especially in ARDS associated with septic shock and neurocritical diseases. The cornerstone of therapy lies in the treatment of the underlying cause and in the use mechanical ventilation which, if inappropriately administered, can lead to ventilator-induced lung injury. Tidal volume = 6 ml/kg of ideal body weight to maintain an end-inspiratory (plateau) pressure = 30 cm H2O ("protective ventilation") is the only variable consistently associated with decreased mortality. Moderate-to-high PEEP levels are frequently required to treat hypoxemia, yet no specific level or titration strategy has improved outcomes. Recently, the use of early prone positioning in patients with PaO2/FIO2 = 150 was associated with increased survival. In severely hypoxemic patients, it may be necessary to use adjuvants of mechanical ventilation as recruitment maneuvers, pressure-controlled modes, neuromuscular blocking agents, and extracorporeal-membrane oxygenation. Fluid restriction appears beneficial.

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.

International study on microcirculatory shock occurrence in acutely ill patients.

OBJECTIVES: Microcirculatory alterations are associated with adverse outcome in subsets of critically ill patients. The prevalence and significance of microcirculatory alterations in the general ICU population are unknown. We studied the prevalence of microcirculatory alterations in a heterogeneous ICU population and its predictive value in an integrative model of macro- and microcirculatory variables. DESIGN: Multicenter observational point prevalence study. SETTING: The Microcirculatory Shock Occurrence in Acutely ill Patients study was conducted in 36 ICUs worldwide. PATIENTS: A heterogeneous ICU population consisting of 501 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic, hemodynamic, and laboratory data were collected in all ICU patients who were 18 years old or older. Sublingual Sidestream Dark Field imaging was performed to determine the prevalence of an abnormal capillary microvascular flow index (< 2.6) and its additional value in predicting hospital mortality. In 501 patients with a median Acute Physiology and Chronic Health Evaluation II score of 15 (10-21), a Sequential Organ Failure Assessment score of 5 (2-8), and a hospital mortality of 28.4%, 17% exhibited an abnormal capillary microvascular flow index. Tachycardia (heart rate > 90 beats/min) (odds ratio, 2.71; 95% CI, 1.67-4.39; p < 0.001), mean arterial pressure (odds ratio, 0.979; 95% CI, 0.963-0.996; p = 0.013), vasopressor use (odds ratio, 1.84; 95% CI, 1.11-3.07; p = 0.019), and lactate level more than 1.5 mEq/L (odds ratio, 2.15; 95% CI, 1.28-3.62; p = 0.004) were independent risk factors for hospital mortality, but not abnormal microvascular flow index. In reference to microvascular flow index, a significant interaction was observed with tachycardia. In patients with tachycardia, the presence of an abnormal microvascular flow index was an independent, additive predictor for in-hospital mortality (odds ratio, 3.24; 95% CI, 1.30-8.06; p = 0.011). This was not true for nontachycardic patients nor for the total group of patients. CONCLUSIONS: In a heterogeneous ICU population, an abnormal microvascular flow index was present in 17% of patients. This was not associated with mortality. However, in patients with tachycardia, an abnormal microvascular flow index was independently associated with an increased risk of hospital death.

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.

Lack of correlation between central venous minus arterial PCO2 to arterial minus central venous O2 content ratio and respiratory quotient in patients with septic shock: A prospective observational study.

OBJECTIVE: Central venous-arterial PCO2 to arterial-central venous O2 content ratio (Pcv-aCO2/Ca-cvO2) is commonly used as a surrogate for respiratory quotient (RQ) and tissue oxygenation. Although Pcv-aCO2/Ca-cvO2 might be associated with hyperlactatemia and outcome, neither the interchangeability with RQ nor the correlation with conclusive variables of anaerobic metabolism has never been demonstrated in septic shock. Our goal was to compare Pcv-aCO2/Ca-cvO2 and RQ in patients with septic shock. DESIGN: Prospective, observational study. SETTING: Two adult ICUs. PATIENTS: Forty-seven patients with septic shock on mechanical ventilation with stable respiratory settings and vasopressor dose after initial resuscitation. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: We measured arterial and central venous gases, Hb, and O2Hb. Pcv-aCO2/Ca-cvO2 and the ratio of central venous-arterial CO2 content to arterial-central venous O2 content (Ccv-aCO2/Ca-cvO2) were calculated. RQ was determined by indirect calorimetry. RESULTS: Pcv-aCO2/Ca-cvO2 and Ccv-aCO2/Ca-cvO2 were not correlated with RQ (R2 = 0.01, P = 0.50 and R2 = 0.01, P = 0.58, respectively), showing large bias and wide 95 % limits of agreement with RQ (1.09, -1.10-3.27 and 0.42, -1.53-2.37). A multiple linear regression model showed Hb, and central venous PCO2 and O2Hb, but not RQ, as Pcv-aCO2/Ca-cvO2 determinants (R2 = 0.36, P = 0.0007). CONCLUSIONS: In patients with septic shock, Pcv-aCO2/Ca-cvO2 did not correlate with RQ and was mainly determined by factors that modify the dissociation of CO2 from Hb. Pcv-aCO2/Ca-cvO2 seems to be a poor surrogate for RQ; therefore, its values should be interpreted with caution.

Role of Pv-aCO2 gradient and Pv-aCO2/Ca-vO2 ratio during cardiac surgery: a retrospective observational study.

INTRODUCTION: Arterial lactate, mixed venous O2 saturation, venous minus arterial CO2 partial pressure (Pv-aCO2) and the ratio between this gradient and the arterial minus venous oxygen content (Pv-aCO2/Ca-vO2) were proposed as markers of tissue hypoperfusion and oxygenation. The main goals were to characterize the determinants of Pv-aCO2 and Pv-aCO2/Ca-vO2, and the interchangeability of the variables calculated from mixed and central venous samples. METHODS: 35 cardiac surgery patients were included. Variables were measured or calculated: after anesthesia induction (T1), end of surgery (T2), and at 6...8.ßhours intervals after ICU admission (T3 and T4). RESULTS: Macrohemodynamics was characterized by increased cardiac index and low systemic vascular resistances after surgery (p.ß<.ß0.05). Hemoglobin, arterial-pH, lactate, and systemic O2 metabolism showed significant changes during the study (p.ß<.ß0.05). Pv-aCO2 remained high and without changes, Pv-aCO2/Ca-vO2 was also high and decreased at T4 (p.ß<.ß0.05). A significant correlation was observed globally and at each time interval, between Pv-aCO2 or Pv-aCO2/Ca-vO2 with factors that may affect the CO2 hemoglobin dissociation. A multilevel linear regression model with Pv-aCO2 and Pv-aCO2/Ca-vO2 as outcome variables showed a significant association for Pv-aCO2 with SvO2, and BE (p.ß<.ß0.05), while Pv-aCO2/Ca-vO2 was significantly associated with Hb, SvO2, and BE (p.ß<.ß0.05) but not with cardiac output. Measurements and calculations from mixed and central venous blood were not interchangeable. CONCLUSIONS: Pv-aCO2 and Pv-aCO2/Ca-vO2 could be influenced by different factors that affect the CO2 dissociation curve, these variables should be considered with caution in cardiac surgery patients. Finally, central venous and mixed values were not interchangeable.