Elisa Estenssoro

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

IntroductionOur goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation.MethodsTwenty 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.ResultsIncreasing 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).ConclusionsPatients 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.

Incidence and clinical effects of intra-abdominal hypertension in critically ill patients

Objective:The objective of this study was to determine the epidemiology and outcomes of intra-abdominal hypertension in a heterogeneous intensive care unit population. Design:This was a prospective cohort study. Setting:This study was conducted at a medical-surgical intensive care unit in a university hospital. Patients:Study patients included all those consecutively admitted during 9 months, staying >24 hrs, and requiring bladder catheterization. Measurements and Main Results:On admission, epidemiologic data and risk factors for intra-abdominal hypertension were studied; then, daily maximal and mean intra-abdominal pressures (IAPmax and IAPmean), abdominal perfusion pressure, fluid balances, filtration gradient, and sequential organ failure assessment score, were registered. IAPs were recorded through a bladder catheter every 6 hrs until death, discharge, or along 7 days. Intra-abdominal hypertension was defined as IAP ≥12 mm Hg. Abdominal compartment syndrome was defined as IAP ≥20 mm Hg plus ≥1 new organ failure. Main outcome measure was hospital mortality. Of 83 patients, considering IAPmax, 31% had intra-abdominal hypertension on admission and another 33% developed it after (23% and 31% with IAPmean). Main risk factors were mechanical ventilation, acute respiratory distress syndrome, and fluid resuscitation (relative risk, 5.26, 3.19, and 2.50, respectively). Patients with intra-abdominal hypertension were sicker, had higher mortality (53% vs. 27%, p = .02), and consistently showed higher total and renal sequential organ failure assessment score, daily and cumulative fluid balances, and lower filtration gradient. Nonsurvivors had higher IAPmax, IAPmean, and fluid balances and lower abdominal perfusion pressure. Abdominal compartment syndrome developed in 12%; 20% survived. Logistic regression identified IAPmax as an independent predictor of mortality (odds ratio, 1.17; 95% confidence interval, 1.05–1.30; p = .003) after adjusting with Acute Physiology and Chronic Health Evaluation II and comorbidities (odds ratio, 1.15; 95% confidence interval, 1.06–1.25; p = .001; and odds ratio, 2.68; 95% confidence interval, 1.27–5.67; p = .013, respectively). Models with IAPmean and abdominal perfusion pressure also performed well. Areas under receiver operating characteristic curves were .81 and .83. Conclusions:Intra-abdominal hypertension, diagnosed either with IAPmax or IAPmean, was frequent and showed an independent association with mortality. Intra-abdominal hypertension was significantly associated with more severe organ failures, particularly renal and respiratory, and a prolonged intensive care unit stay.

Pandemic 2009 Influenza A in Argentina: A Study of 337 Patients on Mechanical Ventilation

RATIONALE The rapid spread of the 2009 Influenza A (H1N1) around the world underscores the need for a better knowledge of epidemiology, clinical features, outcomes, and mortality predictors, especially in the most severe presentations. OBJECTIVES To describe these characteristics in patients with confirmed, probable, and suspected viral pneumonia caused by 2009 influenza A (H1N1) admitted to 35 intensive care units with acute respiratory failure requiring mechanical ventilation in Argentina, between June 3 and September 7. METHODS Inception-cohort study including 337 consecutive adult patients. Data were collected in a form posted on the Argentinian Society of Intensive Care website. MEASUREMENTS AND MAIN RESULTS Proportions of confirmed, probable, or suspected cases were 39%, 8%, and 53% and had similar outcomes. APACHE II was 18 +/- 7; age 47 +/- 17 years; 56% were male; and 64% had underlying conditions, with obesity (24%), chronic obstructive respiratory disease (18%), and immunosupression (15%) being the most common. Seven percent were pregnant. On admission, patients had severe hypoxemia (Pa(O(2))/Fi(O(2)) 140 [87-200]), extensive lung radiologic infiltrates (2.87 +/- 1.03 quadrants) and bacterial coinfection, (25%; mostly with Streptococcus pneumoniae). Use of adjuvants such as recruitment maneuvers (40%) and prone positioning (13%), and shock (72%) and acute kidney injury requiring hemodialysis (17%), were frequent. Mortality was 46%, and was similar across all ages. APACHE II, lowest Pa(O(2))/Fi(O(2)), shock, hemodialysis, prone positioning, and S. pneumoniae coinfection independently predicted death. CONCLUSIONS Patients with 2009 influenza A (H1N1) requiring mechanical ventilation were mostly middle-aged adults, often with comorbidities, and frequently developed severe acute respiratory distress syndrome and multiorgan failure requiring advanced organ support. Case fatality rate was accordingly high.

Clinical Characteristics and Outcomes of Obstetric Patients Requiring ICU Admission

OBJECTIVES To review a series of critically ill obstetric patients admitted to our ICU to assess the spectrum of disease, required interventions, and fetal/maternal mortality, and to identify conditions associated with maternal death. DESIGN Retrospective cohort. SETTING Medical-surgical ICU in a university-affiliated hospital. PATIENTS Pregnant/postpartum admissions between January 1, 1998, and September 30, 2005. INTERVENTIONS None. MEASUREMENTS AND RESULTS We studied 161 patients (age, 28 +/- 9 years; mean gestational age, 29 +/- 9 weeks) [mean +/- SD], constituting 10% of 1,571 hospital admissions. APACHE (acute physiology and chronic health evaluation) II score was 14 +/- 8, with 24% predicted mortality; sequential organ failure assessment score was 5 +/- 3; and therapeutic intervention scoring system at 24 h was 25 +/- 9. Forty-one percent of patients required mechanical ventilation (MV). ARDS, shock, and organ dysfunction were present in 19%, 25%, and 48% of patients, respectively. Most patients (63%) were admitted postpartum, and 74% of admissions were of obstetric cause. Hypertensive disease (40%), major hemorrhage (16%), septic abortion (12%), and nonobstetric sepsis (10%) were the principal diagnoses. Maternal mortality was 11%, with multiple organ dysfunction syndrome (44%) and intracranial hemorrhage (39%) as main causes. There were no differences in death rate in patients admitted for obstetric and nonobstetric causes. Fetal mortality was 32%. Only 30% of patients received antenatal care, which was more frequent in survivors (33% vs 6% nonsurvivors, p = 0.014). CONCLUSIONS Although ARDS, organ failures, shock, and use of MV were extremely frequent in this population, maternal mortality remains within an acceptable range. APACHE II overpredicted mortality in these patients. Septic abortion is still an important modifiable cause of mortality. Efforts should concentrate in increasing antenatal care, which was clearly underprovided in these patients.

Comparison of three different methods of evaluation of metabolic acid-base disorders.

Objectives: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 (HCO−3) and base excess (BE); and b) an approach relying on HCO−3, BE, and albumin-corrected anion gap (AGcorrected). Design:Prospective observational study. Setting:A university-affiliated hospital intensive care unit (ICU). Patients:Nine hundred thirty-five patients admitted to the ICU. Interventions:None. Measurements and Main Results:The Stewart approach detected an arterial metabolic alteration in 131 (14%) of patients with normal HCO−3 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 HCO−3, BE, and AGcorrected. On the other hand, the Stewart approach failed to identify 27 (3%) patients with alterations otherwise observed with the use of HCO−3, 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, HCO−3, and lactates, respectively (SOFA vs. the rest, p < .0001). Conclusions:In this large group of critically ill patients, diagnostic performance of the Stewart approach exceeded that of HCO−3 and BE. However, when AGcorrected was included in the analysis, the Stewart approach did not offer any diagnostic or prognostic advantages.

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.

Persistent villi hypoperfusion explains intramucosal acidosis in sheep endotoxemia.

Objective: To test the hypothesis that persistent villi hypoperfusion explains intramucosal acidosis after endotoxemic shock resuscitation. Design: Controlled experimental study. Setting: University-based research laboratory. Subjects: A total of 14 anesthetized, mechanically ventilated sheep. Interventions: Sheep were randomly assigned to endotoxin (n = 7) or control groups (n = 7). The endotoxin group received 5 &mgr;g/kg endotoxin, followed by 4 &mgr;g·kg−1·hr−1 for 150 mins. After 60 mins of shock, hydroxyethylstarch resuscitation was given to normalize oxygen transport for an additional 90 mins. Measurements and Main Results: 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·min−1·kg−1, and 643 ± 203 vs. 317 ± 93 mL·min−1·kg−1, respectively; p < .05 vs. basal), whereas it increased intramucosal–arterial Pco2 (&Dgr;Pco2) 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·min−1·kg−1), superior mesenteric artery blood flow (683 ± 192 mL·min−1·kg−1), and sublingual and serosal intestinal microvascular flow indexes (2.8 ± 0.5 and 3.5 ± 0.7). Nevertheless, &Dgr;Pco2, 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). Conclusions: 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.

Effects of levosimendan and dobutamine in experimental acute endotoxemia: a preliminary controlled study

ObjectiveTo test the hypothesis that levosimendan increases systemic and intestinal oxygen delivery (DO2) and prevents intramucosal acidosis in septic shock.DesignProspective, controlled experimental study.SettingUniversity-based research laboratory.SubjectsNineteen anesthetized, mechanically ventilated sheep.InterventionsEndotoxin-treated sheep were randomly assigned to three groups: control (n = 7), dobutamine (10 μg/kg/min, n = 6) and levosimendan (100 μg/kg over 10 min followed by 100 μg/kg/h, n = 6) and treated for 120 min.Measurements and main resultsAfter endotoxin administration, systemic and intestinal DO2 decreased (24.6 ± 5.2 vs 15.3 ± 3.4 ml/kg/min and 105.0 ± 28.1 vs 55.8 ± 25.9 ml/kg/min, respectively; p < 0.05 for both). Arterial lactate and the intramucosal–arterial PCO2 difference (ΔPCO2) increased (1.4 ± 0.3 vs 3.1 ± 1.5 mmHg and 9 ± 6 vs 23 ± 6 mmHg mmol/l, respectively; p < 0.05). Systemic DO2 was preserved in the dobutamine-treated group (22.3 ± 4.7 vs 26.8 ± 7.0 ml/min/kg, p = NS) but intestinal DO2 decreased (98.9 ± 0.2 vs 68.0 ± 22.9 ml/min/kg, p < 0.05) and ΔPCO2 increased (12 ± 5 vs 25 ± 11 mmHg, p < 0.05). The administration of levosimendan prevented declines in systemic and intestinal DO2 (25.1 ± 3.0 vs 24.0 ± 6.3 ml/min/kg and 111.1 ± 18.0 vs 98.2 ± 23.1 ml/min/kg, p = NS for both) or increases in ΔPCO2 (7 ± 7 vs 10 ± 8, p = NS). Arterial lactate increased in both the dobutamine and levosimendan groups (1.6 ± 0.3 vs 2.5 ± 0.7 and 1.4 ± 0.4 vs. 2.9 ± 1.1 mmol/l, p = NS between groups).ConclusionsCompared with dobutamine, levosimendan increased intestinal blood flow and diminished intramucosal acidosis in this experimental model of sepsis.

The distinct clinical profile of chronically critically ill patients: a cohort study

IntroductionOur goal was to describe the epidemiology, clinical profiles, outcomes, and factors that might predict progression of critically ill patients to chronically critically ill (CCI) patients, a still poorly characterized subgroup.MethodsWe prospectively studied all patients admitted to a university-affiliated hospital intensive care unit (ICU) between 1 July 2002 and 30 June 2005. On admission, we recorded epidemiological data, the presence of organ failure (multiorgan dysfunction syndrome (MODS)), underlying diseases (McCabe score), acute respiratory distress syndrome (ARDS) and shock. Daily, we recorded MODS, ARDS, shock, mechanical ventilation use, lengths of ICU and hospital stay (LOS), and outcome. CCI patients were defined as those having a tracheotomy placed for continued ventilation. Clinical complications and time to tracheal decannulation were registered. Predictors of progression to CCI were identified by logistic regression.ResultsNinety-five patients (12%) fulfilled the CCI definition and, compared with the remaining 690 patients, these CCI patients were sicker (APACHE II, 21 ± 7 versus 18 ± 9 for non-CCI patients, p = 0.005); had more organ dysfunctions (SOFA 7 ± 3 versus 6 ± 4, p < 0.003); received more interventions (TISS 32 ± 10 versus 26 ± 8, p < 0.0001); and had less underlying diseases and had undergone emergency surgery more frequently (43 versus 24%, p = 0.001). ARDS and shock were present in 84% and 83% of CCI patients, respectively, versus 44% and 48% in the other patients (p < 0.0001 for both). CCI patients had higher expected mortality (38% versus 32%, p = 0.003), but observed mortality was similar (32% versus 35%, p = 0.59). Independent predictors of progression to CCI were ARDS on admission, APACHE II and McCabe scores (odds ratio (OR) 2.26, p < 0.001; OR 1.03, p < 0.01; and OR 0.34, p < 0.0001, respectively). Lengths of mechanical ventilation, ICU and hospital stay were 33 (24 to 50), 39 (29 to 55) and 55 (37 to 84) days, respectively. Tracheal decannulation was achieved at 40 ± 19 days.ConclusionCCI patients were a severely ill population, in which ARDS, shock, and MODS were frequent on admission, and who suffered recurrent complications during their stay. However, their prognosis was equivalent to that of the other ICU patients. ARDS, APACHE II and McCabe scores were independent predictors of evolution to chronicity.

Intramucosal–arterial PCO2 gap fails to reflect intestinal dysoxia in hypoxic hypoxia

IntroductionAn elevation in intramucosal–arterial PCO2 gradient (ΔPCO2) could be determined either by tissue hypoxia or by reduced blood flow. Our hypothesis was that in hypoxic hypoxia with preserved blood flow, ΔPCO2 should not be altered.MethodsIn 17 anesthetized and mechanically ventilated sheep, oxygen delivery was reduced by decreasing flow (ischemic hypoxia, IH) or arterial oxygen saturation (hypoxic hypoxia, HH), or no intervention was made (sham). In the IH group (n = 6), blood flow was lowered by stepwise hemorrhage; in the HH group (n = 6), hydrochloric acid was instilled intratracheally. We measured cardiac output, superior mesenteric blood flow, gases, hemoglobin, and oxygen saturations in arterial blood, mixed venous blood, and mesenteric venous blood, and ileal intramucosal PCO2 by tonometry. Systemic and intestinal oxygen transport and consumption were calculated, as was ΔPCO2. After basal measurements, measurements were repeated at 30, 60, and 90 minutes.ResultsBoth progressive bleeding and hydrochloric acid aspiration provoked critical reductions in systemic and intestinal oxygen delivery and consumption. No changes occurred in the sham group. ΔPCO2 increased in the IH group (12 ± 10 [mean ± SD] versus 40 ± 13 mmHg; P < 0.001), but remained unchanged in HH and in the sham group (13 ± 6 versus 10 ± 13 mmHg and 8 ± 5 versus 9 ± 6 mmHg; not significant).DiscussionIn this experimental model of hypoxic hypoxia with preserved blood flow, ΔPCO2 was not modified during dependence of oxygen uptake on oxygen transport. These results suggest that ΔPCO2 might be determined primarily by blood flow.