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 (ΔPCO₂). 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 ΔPCO₂ 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.

Vasopressors are commonly applied to restore and maintain blood pressure in patients with sepsis. We aimed to evaluate the current practice and therapeutic goals regarding vasopressor use in septic shock as a basis for future studies and to provide some recommendations on their use. From November 2016 to April 2017, an anonymous web-based survey on the use of vasoactive drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 17 questions focused on the profile of respondents, triggering factors, first choice agent, dosing, timing, targets, additional treatments, and effects of vasopressors. We investigated whether the answers complied with current guidelines. In addition, a group of 34 international ESICM experts was asked to formulate recommendations for the use of vasopressors based on 6 questions with sub-questions (total 14). A total of 839 physicians from 82 countries (65% main specialty/activity intensive care) responded. The main trigger for vasopressor use was an insufficient mean arterial pressure (MAP) response to initial fluid resuscitation (83%). The first-line vasopressor was norepinephrine (97%), targeting predominantly a MAP > 60–65 mmHg (70%), with higher targets in patients with chronic arterial hypertension (79%). The experts agreed on 10 recommendations, 9 of which were based on unanimous or strong (≥ 80%) agreement. They recommended not to delay vasopressor treatment until fluid resuscitation is completed but rather to start with norepinephrine early to achieve a target MAP of ≥ 65 mmHg. Reported vasopressor use in septic shock is compliant with contemporary guidelines. Future studies should focus on individualized treatment targets including earlier use of vasopressors.

The Stewart approach states that pH is primarily determined by Pco2, strong ion difference (SID), and nonvolatile weak acids. This method might identify severe metabolic disturbances that go undetected by traditional analysis. Our goal was to compare diagnostic and prognostic performances of the Stewart approach with a) the traditional analysis based on bicarbonate (HCO3) and base excess (BE); and b) an approach relying on HCO3, BE, and albumin-corrected anion gap (AGcorrected). Prospective observational study. A university-affiliated hospital intensive care unit (ICU). Nine hundred thirty-five patients admitted to the ICU. None. The Stewart approach detected an arterial metabolic alteration in 131 (14%) of patients with normal HCO3- and BE, including 120 (92%) patients with metabolic acidosis. However, 108 (90%) of these patients had an increased AGcorrected. The Stewart approach permitted the additional diagnosis of metabolic acidosis in only 12 (1%) patients with normal HCO3, BE, and AGcorrected. On the other hand, the Stewart approach failed to identify 27 (3%) patients with alterations otherwise observed with the use of HCO3-, BE, and AGcorrected (16 cases of acidosis and 11 of alkalosis). SID and BE, and strong ion gap (SIG) and AGcorrected, were tightly correlated (R2 = .86 and .97, p < .0001 for both) with narrow 95% limits of agreement (8 and 3 mmol/L, respectively). Areas under receiver operating characteristic curves to predict 30-day mortality were 0.83, 0.62, 0.61, 0.60, 0.57, 0.56, and 0.67 for Sepsis-related Organ Failure Assessment (SOFA) score, SIG, AGcorrected, SID, BE, HCO3-, and lactates, respectively (SOFA vs. the rest, p < .0001). In this large group of critically ill patients, diagnostic performance of the Stewart approach exceeded that of HCO3- and BE. However, when AGcorrected was included in the analysis, the Stewart approach did not offer any diagnostic or prognostic advantages.

This study was performed to compare intestinal and sublingual microcirculation and their response to a fluid challenge.

To test the hypothesis that persistent villi hypoperfusion explains intramucosal acidosis after endotoxemic shock resuscitation. Controlled experimental study. University-based research laboratory. A total of 14 anesthetized, mechanically ventilated sheep. Sheep were randomly assigned to endotoxin (n = 7) or control groups (n = 7). The endotoxin group received 5 microg/kg endotoxin, followed by 4 microg x kg(-1) x hr(-1) for 150 mins. After 60 mins of shock, hydroxyethylstarch resuscitation was given to normalize oxygen transport for an additional 90 mins. Endotoxin infusion decreased mean arterial blood pressure, cardiac output, and superior mesenteric artery blood flow (96 +/- 10 vs. 51 +/- 20 mm Hg, 145 +/- 30 vs. 90 +/- 30 mL x min(-1) x kg(-1), and 643 +/- 203 vs. 317 +/- 93 mL x min(-1) x kg(-1), respectively; p < .05 vs. basal), whereas it increased intramucosal-arterial PCO2 (deltaPCO2) and arterial lactate (3 +/- 3 vs. 14 +/- 8 mm Hg, and 1.5 +/- 0.5 vs. 3.7 +/- 1.3 mmol/L; p < .05). Sublingual, and serosal and mucosal intestinal microvascular flow indexes, and the percentage of perfused ileal villi were reduced (3.0 +/- 0.1 vs. 2.3 +/- 0.4, 3.2 +/- 0.2 vs. 2.4 +/- 0.6, 3.0 +/- 0.0 vs. 2.0 +/- 0.2, and 98% +/- 3% vs. 76% +/- 10%; p < .05). Resuscitation normalized mean arterial blood pressure (92 +/- 13 mm Hg), cardiac output (165 +/- 32 mL x min(-1) x kg(-1)), superior mesenteric artery blood flow (683 +/- 192 mL x min(-1) x kg(-1)), and sublingual and serosal intestinal microvascular flow indexes (2.8 +/- 0.5 and 3.5 +/- 0.7). Nevertheless, deltaPCO2, lactate, mucosal intestinal microvascular flow indexes, and percentage of perfused ileal villi remained altered (10 +/- 6 mm Hg, 3.7 +/- 0.9 mmol/L, 2.3 +/- 0.4, and 78% +/- 11%; p < .05). In this model of endotoxemia, fluid resuscitation corrected both serosal intestinal and sublingual microcirculation but was unable to restore intestinal mucosal perfusion. Intramucosal acidosis might be due to persistent villi hypoperfusion.