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Objective: To evaluate the effects of dobutamine on microcirculatory blood flow alterations in patients with septic shock.Design: Prospective, open-label study.Setting: A 31-bed, medico-surgical intensive care unit of a university hospital.Patients: Twenty-two patients with septic shock.Interventions: Intravenous administration of dobutamine (5 mug/kg.min) for 2 hrs (n = 22) followed by the addition of 10 M acetylcholine (topically applied, n = 10).Measurements and Main Results: Complete hemodynamic measurements were obtained before and after dobutamine administration. In addition, the sublingual microcirculation was investigated with an orthogonal polarization spectral imaging technique before and after dobutamine administration and after topical application of acetylcholine. Dobutamine significantly improved capillary perfusion (from 48 +/- 15 to 67 +/- 11%, p = .001), but with large individual variation, whereas capillary density remained stable. The addition of topical acetylcholine completely restored capillary perfusion (98 +/- 1%, p = .001) and capillary density. The changes in capillary perfusion during dobutamine administration were not related to changes in cardiac index (p = .45) or arterial pressure (p = .29). Interestingly, the decrease in lactate levels was proportional to the improvement in capillary perfusion (y = 0.07 - 0.02x, r = .46, p = .005) but not to changes in cardiac index (p = .55).Conclusions: The administration of 5 mug/kg.min dobutamine can improve but not restore capillary perfusion in patients with septic shock. These changes are independent of changes in systemic hemodynamic variables. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the effects of different doses of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in patients with septic shock. DESIGN: Prospective, randomized, open-label study. SETTING: A 31-bed, medicosurgical intensive care unit of a university hospital. PATIENTS: Convenience sample of 20 patients with septic shock, separated into two groups according to whether (moderate shock group, n = 10) or not (severe shock, n = 10) dopamine alone was able maintain mean arterial pressure >65 mm Hg. INTERVENTIONS: Dopamine was progressively withdrawn and replaced successively by norepinephrine and then epinephrine (the order of the two agents was randomly determined) to maintain mean arterial pressure constant (moderate shock) or to increase mean arterial pressure above 65 mm Hg (severe shock). MEASUREMENTS AND MAIN RESULTS: Systemic circulation (pulmonary artery catheter) and splanchnic circulation (indocyanine green dilution and hepatic vein catheter) and gastric mucosal Pco(2) (gas tonometry) were measured during dopamine (moderate shock only), norepinephrine, and epinephrine administration (both groups). Data were analyzed with nonparametric tests and are presented as median [percentiles 25-75]. In moderate shock, cardiac index was similar to dopamine and norepinephrine (3.1 [2.7-3.8] vs. 2.9 [2.7-4.1] L/min.m2, p = nonsignificant) but greater with epinephrine (4.1 [3.5-4.4] p <.01 vs. dopamine and norepinephrine). Splanchnic blood flow was similar with the three agents (732 [413-1483] vs. 746 [470-1401] vs. 653 [476-1832] mL/min.m, p = nonsignificant). The gradient between mixed-venous and hepatic venous oxygen saturations was lower with dopamine than with norepinephrine and epinephrine, but the Pco(2) gap was similar with the three agents. In severe shock, cardiac index was higher, but splanchnic blood flow was lower, with epinephrine than with norepinephrine (4.6 [3.7-5.3] vs. 3.4 [3.0-4.1] L/min.m2, p <.01 and 860 [684-1334] vs. 977 [806-1802] mL/min.m2, p <.05, respectively). Epinephrine increased the mixed-venous and hepatic venous oxygen saturation gradient but did not alter Pco(2) gap. CONCLUSIONS: Dopamine and norepinephrine have similar hemodynamic effects, but epinephrine can impair splanchnic circulation in severe septic shock. [ABSTRACT FROM AUTHOR]

Objectives: Anemia is common after acute brain injury and can be associated with brain tissue hypoxia. RBC transfusion (RBCT) can improve brain oxygenation; however, predictors of such improvement remain unknown. We aimed to identify the factors associated with PbtO2 increase (greater than 20% from baseline value) after RBCT, using a generalized mixed model., Design: This is a multicentric retrospective cohort study (2012-2020)., Setting: This study was conducted in three European ICUs of University Hospitals located in Belgium, Switzerland, and Austria., Patients: All patients with acute brain injury who were monitored with brain tissue oxygenation (PbtO2) catheters and received at least one RBCT., Intervention: Patients received at least one RBCT. PbtO2 was recorded before, 1 hour, and 2 hours after RBCT., Measurements and Main Results: We included 69 patients receiving a total of 109 RBCTs after a median of 9 days (5-13 d) after injury. Baseline hemoglobin (Hb) and PbtO2 were 7.9 g/dL [7.3-8.7 g/dL] and 21 mm Hg (16-26 mm Hg), respectively; 2 hours after RBCT, the median absolute Hb and PbtO2 increases from baseline were 1.2 g/dL [0.8-1.8 g/dL] (p = 0.001) and 3 mm Hg (0-6 mm Hg) (p = 0.001). A 20% increase in PbtO2 after RBCT was observed in 45 transfusions (41%). High heart rate (HR) and low PbtO2 at baseline were independently associated with a 20% increase in PbtO2 after RBCT. Baseline PbtO2 had an area under receiver operator characteristic of 0.73 (95% CI, 0.64-0.83) to predict PbtO2 increase; a PbtO2 of 20 mm Hg had a sensitivity of 58% and a specificity of 73% to predict PbtO2 increase after RBCT., Conclusions: Lower PbtO2 values and high HR at baseline could predict a significant increase in brain oxygenation after RBCT., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: To assess the role of thromboprophylaxis regimens on the occurrence of pulmonary embolism in coronavirus disease 2019 patients., Design: Retrospective analysis of prospectively collected data on coronavirus disease 2019 patients, included between March 10, and April 30, 2020., Setting: ICU of an University Hospital in Belgium., Patients and Interventions: Critically ill adult mechanically ventilated coronavirus disease 2019 patients were eligible if they underwent a CT pulmonary angiography, as part of the routine management in case of persistent hypoxemia or respiratory deterioration. The primary endpoint of this study was the occurrence of pulmonary embolism according to the use of standard thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units once daily) or high regimen thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units bid or therapeutic unfractioned heparin)., Measurements and Main Results: Of 49 mechanically ventilated coronavirus disease 2019, 40 underwent CT pulmonary angiography after a median of 7 days (4-8 d) since ICU admission and 12 days (9-16 d) days since the onset of symptoms. Thirteen patients (33%) were diagnosed of pulmonary embolism, which was bilateral in six patients and localized in the right lung in seven patients. D-dimers on the day of CT pulmonary angiography had a predictive accuracy of 0.90 (95% CIs: 0.78-1.00) for pulmonary embolism. The use of high-regimen thromboprophylaxis was associated with a lower occurrence of pulmonary embolism (2/18; 11%) than standard regimen (11/22, 50%-odds ratio 0.13 [0.02-0.69]; p = 0.02); this difference remained significant even after adjustment for confounders. Six patients with pulmonary embolism (46%) and 14 patients without pulmonary embolism (52%) died at ICU discharge (odds ratio 0.79 [0.24-3.26]; p = 0.99)., Conclusions: In this study, one third of coronavirus disease 2019 mechanically ventilated patients have a pulmonary embolism visible on CT pulmonary angiography. High regimen thromboprophylaxis may decrease the occurrence of such complication.

Objectives: Skin blood flow is rapidly altered during circulatory shock and may remain altered despite apparent systemic hemodynamic stabilization. We evaluated whether changes in skin blood flow during circulatory shock were related to survival., Design: Prospective study., Setting: Thirty-five-bed medical-surgical university hospital department of intensive care., Subjects: Twenty healthy volunteers and 70 patients with circulatory shock (< 12 hr duration), defined as the need for vasopressors to maintain mean arterial pressure greater than or equal to 65 mm Hg and signs of altered tissue perfusion., Interventions: We assessed skin blood flow using skin laser Doppler on the fingertip for 3 minutes at basal temperature (SBFBT) and at 37°C (SBF37) (thermal challenge test) once in volunteers and at the time of inclusion and after 6, 24, 48, 72, and 96 hours in patients with shock. Capillary refill time and peripheral perfusion index were measured at the same time points on the contralateral hand., Measurements and Main Results: The thermal challenge response (ΔSBF/ΔT) was calculated using the following formula: (SBF37-SBFBT)/(37-basal temperature). Area under the receiver operating characteristic curves were calculated to evaluate variables predictive of ICU mortality. At inclusion, skin blood flow and ΔSBF/ΔT were lower in patients than in volunteers. Baseline skin blood flow (31 [17-113] vs 16 [9-32] arbitrary perfusion units; p = 0.01) and ΔSBF/ΔT (4.3 [1.7-10.9] vs 0.9 [0.4-2.9] arbitrary perfusion unit/s) were greater in survivors than in nonsurvivors. Capillary refill time was shorter in survivors than in nonsurvivors; peripheral perfusion index was similar in the two groups. ΔSBF/ΔT (area under the receiver operating characteristic curve 0.94 [0.88-0.99]) and SBFBT (area under the receiver operating characteristic curve 0.83 [0.73-0.93]) had the best predictive value for ICU mortality with cutoff values less than or equal to 1.25 arbitrary perfusion unit/°C (sensitivity 88%, specificity 89%) and less than or equal to 21 arbitrary perfusion unit (sensitivity 84%, specificity 81%), respectively., Conclusions: Alterations in fingertip skin blood flow can be evaluated using a laser Doppler thermal challenge technique in patients with circulatory shock and are directly related to outcome. These novel monitoring techniques could potentially be used to guide resuscitation.

Objectives: RBC transfusions can increase oxygen availability to the tissues, but studies have provided conflicting results. The objectives of this study were, therefore, to evaluate, using systematic review and meta-analysis, the effects of transfusion on hemodynamic/oxygenation variables in patients without acute bleeding., Data Sources: PubMed, Scopus, Cochrane Database of Systematic Reviews, and Embase from inception until June 30, 2019., Study Selection: All articles that reported values of prespecified hemodynamic or oxygenation variables before and after RBC transfusion., Data Extraction: Publication year, number of patients, number of transfusions and the type of population studied, hemodynamic and oxygenation data (heart rate, cardiac index, mixed venous oxygen saturation or central venous oxygen saturation, oxygen delivery index, oxygen consumption index, oxygen extraction ratio, arteriovenous oxygen difference and arterial blood lactate) before and after transfusion. We performed a meta-analysis for each variable for which there were sufficient data to estimate mean differences. We also performed subgroup analyses comparing septic with nonseptic patients., Data Synthesis: We retrieved 6,420 studies; 33 met the inclusion criteria, 14 of which were in patients with sepsis. In the meta-analysis, the estimated mean differences and 95% CIs comparing the periods before and after transfusion were -0.0 L/min/m (-0.1 to 0.1 L/min/m) (p = 0.86) for cardiac index; -1.8 beats/min (-3.7 to 0.1 beats/min) (p = 0.06) for heart rate; 96.8 mL/min/m (71.1-122.5 mL/min/m) (p < 0.01) for oxygen delivery index; 2.9% (2.2-3.5%) (p < 0.01) for mixed venous oxygen saturation or central venous oxygen saturation; -3.7% (-4.4% to -3.0%) (p < 0.01) for oxygen extraction ratio; and 4.9 mL/min/m (0.9-9.0 mL/min/m) (p = 0.02) for oxygen consumption index. The estimated mean difference for oxygen consumption index in the patients with sepsis was 8.4 mL/min/m (2.3-14.5 mL/min/m; p = 0.01)., Conclusions: Transfusion was not associated with a decrease in mean cardiac output or mean heart rate. The increase in mean oxygen delivery following transfusion was associated with an increase in mean oxygen consumption after transfusion, especially in patients with sepsis.

Objectives: To characterize renin in critically ill patients. Renin is fundamental to circulatory homeostasis and could be a useful marker of tissue-perfusion. However, diurnal variation, continuous renal replacement therapy and drug-interference could confound its use in critical care practice., Design: Prospective observational study., Setting: Single-center, mixed medical-surgical ICU in Europe., Patients: Patients over 18 years old with a baseline estimated glomerular filtration rate greater than 30 mL/min/1.73 m and anticipated ICU stay greater than 24 hours. Informed consent was obtained from the patient or next-of-kin., Interventions: Direct plasma renin was measured in samples drawn 6-hourly from arterial catheters in recumbent patients and from extracorporeal continuous renal replacement therapy circuits. Physiologic variables and use of drugs that act on the renin-angiotensin-aldosterone system were recorded prospectively. Routine lactate measurements were used for comparison., Measurements and Main Results: One-hundred twelve arterial samples (n = 112) were drawn from 20 patients (65% male; mean ± SD, 60 ± 14 yr old) with septic shock (30%), hemorrhagic shock (15%), cardiogenic shock (20%), or no circulatory shock (35%). The ICU mortality rate was 30%. Renin correlated significantly with urine output (repeated-measures correlation coefficient = -0.29; p = 0.015) and mean arterial blood pressure (repeated-measures correlation coefficient = -0.35; p < 0.001). There was no diurnal variation of renin or significant interaction of renin-angiotensin-aldosterone system drugs with renin in this population. Continuous renal replacement therapy renin removal was negligible (mass clearance ± SD 4% ± 4.3%). There was a significant difference in the rate of change of renin over time between survivors and nonsurvivors (-32 ± 26 μU/timepoint vs +92 ± 57 μU/timepoint p = 0.03; mean ± SEM), but not for lactate (-0.14 ± 0.04 mM/timepoint vs +0.15 ± 0.21 mM/timepoint; p = 0.07). Maximum renin achieved significant prognostic value for ICU mortality (receiver operator curve area under the curve 0.80; p = 0.04), whereas maximum lactate did not (receiver operator curve area under the curve, 0.70; p = 0.17)., Conclusions: In an heterogeneous ICU population, renin measurement was not significantly affected by diurnal variation, continuous renal replacement therapy, or drugs. Renin served as a marker of tissue-perfusion and outperformed lactate as a predictor of ICU mortality.

Objective: To review current knowledge about cell-free hemoglobin solutions., Data Source: A computerized MEDLINE search was used to retrieve all studies concerning cell-free hemoglobin solutions from 1990 to 2003. The reference lists of all available review articles and primary studies were also reviewed to identify references not identified in the computerized search., Study Selection: All clinical and experimental studies involving cell-free hemoglobin solutions were included., Data Extraction: From the selected studies, information was obtained regarding the experimental model or the study population in which cell-free hemoglobin solutions were investigated, the type of cell-free hemoglobin solution used, their deleterious or beneficial effects, and their possible indications., Data Synthesis: In many studies, hemoglobin solutions were considered as efficient resuscitative agents and good alternatives to red blood cell transfusion, owing to their marked vasopressor effect, coupled with their capacity to improve the microcirculation and rapidly restore metabolic parameters. The main problems identified include excessive systemic vasoconstriction and oxidative damage. Initial enthusiasm in the development of hemoglobin solutions has been tempered recently by the negative results of a U.S. multicenter trial studying the early infusion of diaspirin cross-linked hemoglobin in trauma patients. Nevertheless, the properties of diaspirin cross-linked hemoglobin (and particularly the strong vasopressor effects) cannot be attributed to all hemoglobin solutions, and results of new clinical studies are eagerly awaited to evaluate the potential benefit of such solutions in the management of trauma patients., Conclusions: Today, we are aware of the effects of the first generation of blood substitutes. Further research is ongoing into newer solutions. One area of interest is the development of new molecular structures to decrease nitric oxide binding, thus minimizing any adverse events and maximizing potential benefits. Nevertheless, possible adverse effects need to be carefully evaluated before these agents can be widely administered.

Objective: To investigate the role of the splanchnic region in the hyperlactatemia of septic patients., Design: Prospective, observational study., Setting: Thirty-one-bed mixed medicosurgical intensive care unit., Patients: Ninety invasively monitored and mechanically ventilated patients with severe sepsis., Measurements and Main Results: Splanchnic lactate balance was measured in all patients. Splanchnic blood flow was determined by using the primed continuous indocyanine green infusion technique in 69 patients. In 71 patients, gastric mucosal Pco2 and the Pco2 gap (the difference between gastric and arterial Pco2) also were determined by using gas tonometry with an automated gas analyzer. In each patient, arterial, mixed-venous, and hepatic venous blood samples were obtained to determine hemoglobin oxygen saturations and lactate concentrations. Arterial and hepatic venous lactate concentrations were determined in triplicate and were averaged, and the arterial hepatic venous difference in lactate and lactate consumption were calculated. The splanchnic region produced lactate in only six of the 90 patients. Mean arterial pressure, cardiac index, arterial lactate, hepatic venous oxygen saturation, and catecholamine use were similar in the six patients with splanchnic lactate production and in the 84 others. The arterial hepatic venous differences in lactate and splanchnic lactate consumption were related directly to arterial lactate concentrations (y = 0.073x + 0.209, r(2) =.06, p <.05, and y = 0.06x + 0.183, r(2) =.08, p <.05, respectively) but were not related to Pco2 gap, to the gradient between mixed-venous and hepatic venous oxygen saturations, or to bilirubin concentrations., Conclusions: Splanchnic lactate release is uncommon in septic patients, even when hyperlactatemia is severe.

Objective: To define whether the gastric mucosal-arterial PCO2 gradient (PCO2 gap) reliably reflects hepatosplanchnic oxygenation in septic patients., Design: Prospective observational clinical study., Setting: An adult, 31-bed medical/surgical department of intensive care of a university hospital., Patients: A total of 36 hemodynamically stable, invasively monitored, mechanically ventilated, sedated, paralyzed patients with severe sepsis., Interventions: In each patient, hepatosplanchnic blood flow was determined by the continuous indocyanine green infusion technique and gastric mucosal PCO2 by the saline tonometry technique. Suprahepatic venous blood oxygen saturation and PCO2 also were measured. The mesenteric veno-arterial PCO2 gradient was determined as the difference between the suprahepatic venous blood PCO2 and the arterial blood PCO2., Measurements and Main Results: There were significant correlations between the hepatosplanchnic blood flow and the suprahepatic venous blood oxygen saturation (r2 = .56; p<.01), between the hepatosplanchnic blood flow and the mesenteric veno-arterial PCO2 gradient (r2 = .55; p<.01), and also between the suprahepatic venous blood oxygen saturation and the mesenteric veno-arterial PCO2 gradient (r2 = .64; p<.01). There was no statistically significant correlation between the PCO2 gap and the hepatosplanchnic blood flow, the suprahepatic venous blood oxygen saturation or the mesenteric veno-arterial PCO2 gradient., Conclusions: In stable septic patients, the PCO2 gap is not correlated with global indexes of gut oxygenation. The interpretation of PCO2 gap is more complex than previously thought.