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Objective: To evaluate if the reductions in systemic and renal oxygen consumption are associated with the development of evidence of anaerobic metabolism., Methods: This is a subanalysis of a previously published study. In anesthetized and mechanically ventilated sheep, we measured the respiratory quotient by indirect calorimetry and its systemic, renal, and intestinal surrogates (the ratios of the venous-arterial carbon dioxide pressure and content difference to the arterial-venous oxygen content difference. The Endotoxemic Shock Group (n = 12) was measured at baseline, after 60 minutes of endotoxemic shock, and after 60 and 120 minutes of fluid and norepinephrine resuscitation, and the values were compared with those of a Control Group (n = 12) without interventions., Results: Endotoxemic shock decreased systemic and renal oxygen consumption (6.3 [5.6 - 6.6] versus 7.4 [6.3 - 8.5] mL/minute/kg and 3.7 [3.3 - 4.5] versus 5.4 [4.6 - 9.4] mL/minute/100g; p < 0.05 for both). After 120 minutes of resuscitation, systemic oxygen consumption was normalized, but renal oxygen consumption remained decreased (6.3 [5.9 - 8.2] versus 7.1 [6.1 - 8.6] mL/minute/100g; p = not significance and 3.8 [1.9 - 4.8] versus 5.7 [4.5 - 7.1]; p < 0.05). The respiratory quotient and the systemic, renal and intestinal ratios of the venous-arterial carbon dioxide pressure and content difference to the arterial-venous oxygen content difference did not change throughout the experiments., Conclusion: In this experimental model of septic shock, oxygen supply dependence was not associated with increases in the respiratory quotient or its surrogates. Putative explanations for these findings are the absence of anaerobic metabolism or the poor sensitivity of these variables in detecting this condition.

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. O 2 consumption (VO 2 ) 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, VO 2 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/mm 2 , PNS) and villi capillaries (14.7 [13.6-16.8] vs. 16.3 [14.2-16.9] mm/mm 2 , PNS), and normalized in sublingual mucosa (19.1 [16.0-20.3] vs. 16.6 [14.7-17.2] mm/mm 2 , 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Although hypothermia is independently associated with an increased mortality in trauma patients, it might be an effective therapeutic approach for otherwise lethal hemorrhage. The effect of hypothermia on microcirculation, however, has been poorly studied in this setting. Our goal was to characterize the effects of hypothermia on microcirculation in normal conditions and in severe hemorrhagic shock., Methods: In anesthetized and mechanically ventilated sheep, we measured cardiac output (CO), renal blood flow (RBF), and systemic and renal O2 consumption (VO2). Cortical renal, intestinal villi, and sublingual microcirculation was assessed by IDF-videomicroscopy. After basal measurements, sheep were assigned to hypothermia (n = 12) and normothermia (n = 12) groups. Central temperature was reduced to ∼34°C and maintained at baseline in each group, respectively. Measurements were repeated after 1 h of hemodynamic stable conditions and 1 h of severe hemorrhagic shock., Results: In conditions of hemodynamic stability, the hypothermia group showed lower CO, RBF, and systemic and renal VO2 than the normothermia group. Red blood cell velocity was also lower in renal, villi, and sublingual microvascular beds (836 ± 195 vs. 1,066 ± 162, 916 ± 105 vs. 1051 ± 41, and 970 ± 182 vs. 1,102 ± 49 μm/s, respectively; P < 0.0001 for all). In hemorrhagic shock, most of the microvascular variables were similarly compromised in both the groups. In hypo- and normothermia groups, the percentage of reduction in perfused vascular density was higher in renal than in intestinal and sublingual microcirculation (66 ± 31 vs. 31 ± 23 and 15 ± 15%, and 78 ± 26 vs. 32 ± 37 and 18 ± 21%, P < 0.01 for both)., Conclusions: This is the first experimental study assessing the effect of systemic hypothermia on microcirculation in severe hemorrhagic shock. The main finding was that hypothermia did not hamper additionally the microcirculatory derangements induced by hemorrhagic shock. In addition, renal microcirculation was more susceptible to hemorrhagic shock than villi and sublingual microcirculation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by the Shock Society.)

The pathophysiology of renal failure in septic shock is complex. Although microvascular dysfunction has been proposed as a mechanism, there are controversial findings about the characteristics of microvascular redistribution and the effects of resuscitation. Our hypothesis was that the normalization of systemic hemodynamics with fluids and norepinephrine fails to improve acute kidney injury. To test this hypothesis, we assessed systemic and renal hemodynamics and oxygen metabolism in 24 anesthetized and mechanically ventilated sheep. Renal cortical microcirculation was evaluated by SDF-videomicroscopy. Shock ( n = 12) was induced by intravenous administration of endotoxin. After 60 min of shock, 30 mL/kg of saline solution was infused and norepinephrine was titrated to reach a mean blood pressure of 70 mmHg for 2 h. These animals were compared with a sham group ( n = 12). After endotoxin administration, mean blood pressure, cardiac index, and systemic O 2 transport and consumption decreased ( P < 0.05 for all). Resuscitation improved these variables. Endotoxin shock also reduced renal blood flow and O 2 transport and consumption (205[157-293] vs. 131 [99-185], 28.4[19.0-38.2] vs. 15.8[13.5-23.2], and 5.4[4.0-8.8] vs. 3.7[3.3-4.5] mL·min -1 ·100 g -1 , respectively); cortical perfused capillary density (23.8[23.5-25.9] vs. 17.5[15.1-19.0] mm/mm 2 ); and creatinine clearance (62.4[39.2-99.4] vs. 10.7[4.4-23.5] mL/min). After 2 h of resuscitation, these variables did not improve (174[91-186], 20.5[10.8-22.7], and 3.8[1.9-4.8] mL·min -1 ·100 g -1 , 19.9[18.6-22.1] mm/mm 2 , and 5.9[1.0-11.9] mL/min). In conclusion, endotoxin shock induced severe renal failure associated with decreased renal flow, O 2 transport and consumption, and cortical microcirculation. Normalization of systemic hemodynamics with fluids and norepinephrine failed to improve renal perfusion, oxygenation, and function. NEW & NOTEWORTHY This experimental model of endotoxin shock induced severe renal failure, which was associated with abnormalities in renal regional blood flow, microcirculation, and oxygenation. Derangements included the compromise of peritubular microvascular perfusion. Improvements in systemic hemodynamics through fluids and norepinephrine were unable to correct these abnormalities.

Background: The microvascular reperfusion injury after retransfusion has not been completely characterized. Specifically, the question of heterogeneity among different microvascular beds needs to be addressed. In addition, the identification of anaerobic metabolism is elusive. The venoarterial PCO 2 to arteriovenous oxygen content difference ratio (P v-a CO 2 /C a-v O 2 ) might be a surrogate for respiratory quotient, but this has not been validated. Therefore, our goal was to characterize sublingual and intestinal (mucosal and serosal) microvascular injury after blood resuscitation in hemorrhagic shock and its relation with O 2 and CO 2 metabolism., Methods: Anesthetized and mechanically ventilated sheep were assigned to stepwise bleeding and blood retransfusion (n = 10) and sham (n = 7) groups. We performed analysis of expired gases, arterial and mixed venous blood gases, and intestinal and sublingual videomicroscopy., Results: In the bleeding group during the last step of hemorrhage, and compared to the sham group, there were decreases in oxygen consumption (3.7 [2.8-4.6] vs. 6.8 [5.8-8.0] mL min -1  kg -1 , P < 0.001) and increases in respiratory quotient (0.96 [0.91-1.06] vs. 0.72 [0.69-0.77], P < 0.001). Retransfusion normalized these variables. The P v-a CO 2 /C a-v O 2 increased in the last step of bleeding (2.4 [2.0-2.8] vs. 1.1 [1.0-1.3], P < 0.001) and remained elevated after retransfusion, compared to the sham group (1.8 [1.5-2.0] vs. 1.1 [0.9-1.3], P < 0.001). P v-a CO 2 /C a-v O 2 had a weak correlation with respiratory quotient (Spearman R = 0.42, P < 0.001). All the intestinal and sublingual microcirculatory variables were affected during hemorrhage and improved after retransfusion. The recovery was only complete for intestinal red blood cell velocity and sublingual total and perfused vascular densities., Conclusions: Although there were some minor differences, intestinal and sublingual microcirculation behaved similarly. Therefore, sublingual mucosa might be an adequate window to track intestinal microvascular reperfusion injury. Additionally, P v-a CO 2 /C a-v O 2 was poorly correlated with respiratory quotient, and its physiologic behavior was different. Thus, it might be a misleading surrogate for anaerobic metabolism.

Background: The identification of anaerobic metabolism in critically ill patients is a challenging task. Observational studies have suggested that the ratio of venoarterial PCO 2 (P v-a CO 2 ) to arteriovenous oxygen content difference (C a-v O 2 ) might be a good surrogate for respiratory quotient (RQ). Yet P v-a CO 2 /C a-v O 2 might be increased by other factors, regardless of anaerobic metabolism. At present, comparisons between P v-a CO 2 /C a-v O 2 and RQ have not been performed. We sought to compare these variables during stepwise hemorrhage and hemodilution. Since anemia predictably produces augmented P v-a CO 2 and decreased C a-v O 2 , our hypothesis was that P v-a CO 2 /C a-v O 2 might be an inadequate surrogate for RQ., Methods: This is a subanalysis of a previously published study. In anesthetized and mechanically ventilated sheep (n = 16), we compared the effects of progressive hemodilution and hemorrhage by means of expired gases analysis., Results: There were comparable reductions in oxygen consumption and increases in RQ in the last step of hemodilution and hemorrhage. The increase in P v-a CO 2 /C a-v O 2 was higher in hemodilution than in hemorrhage (1.9 ± 0.2 to 10.0 ± 0.9 vs. 1.7 ± 0.2 to 2.5 ± 0.1, P < 0.0001). The increase in P v-a CO 2 was lower in hemodilution (6 ± 0 to 10 ± 1 vs. 6 ± 0 to 17 ± 1 mmHg, P < 0.0001). Venoarterial CO 2 content difference and C a-v O 2 decreased in hemodilution and increased in hemorrhage (2.6 ± 0.3 to 1.2 ± 0.1 vs. 2.8 ± 0.2 to 6.9 ± 0.5, and 3.4 ± 0.3 to 1.0 ± 0.3 vs. 3.6 ± 0.3 to 6.8 ± 0.3 mL/dL, P < 0.0001 for both). In hemodilution, P v-a CO 2 /C a-v O 2 increased before the fall in oxygen consumption and the increase in RQ. P v-a CO 2 /C a-v O 2 was strongly correlated with Hb (R 2  = 0.79, P < 0.00001) and moderately with RQ (R 2  = 0.41, P < 0.0001). A multiple linear regression model found Hb, RQ, base excess, and mixed venous oxygen saturation and PCO 2 as P v-a CO 2 /C a-v O 2 determinants (adjusted R 2  = 0.86, P < 0.000001)., Conclusions: In hemodilution, P v-a CO 2 /C a-v O 2 was considerably increased, irrespective of the presence of anaerobic metabolism. P v-a CO 2 /C a-v O 2 is a complex variable, which depends on several factors. As such, it was a misleading indicator of anaerobic metabolism in hemodilution.

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.

The alterations in O2 extraction in hemodilution have been linked to fast red blood cell (RBC) velocity, which might affect the complete release of O2 from Hb. Fast RBC velocity might also explain the normal mucosal-arterial Pco2 (ΔPco2). Yet sublingual and intestinal microcirculation have not been completely characterized in extreme hemodilution. Our hypothesis was that the unchanged ΔPco2 in hemodilution depends on the preservation of villi microcirculation. For this purpose, pentobarbital-anesthetized and mechanically ventilated sheep were submitted to stepwise hemodilution (n = 8), hemorrhage (n = 8), or no intervention (sham, n = 8). In both hypoxic groups, equivalent reductions in O2 consumption (V̇o2) were targeted. Microcirculation was assessed by videomicroscopy, intestinal ΔPco2 by air tonometry, and V̇o2 by expired gases analysis. Although cardiac output and superior mesenteric flow increased in hemodilution, from the very first step (Hb = 5.0 g/dl), villi functional vascular density and RBC velocity decreased (21.7 ± 0.9 vs. 15.9 ± 1.0 mm/mm(2) and 1,033 ± 75 vs. 850 ± 79 μm/s, P < 0.01). In the last stage (Hb = 1.2 g/dl), these variables were lower in hemodiution than in hemorrhage (11.1 ± 0.5 vs. 15.4 ± 0.9 mm/mm(2) and 544 ± 26 vs. 686 ± 70 μm/s, P < 0.01), and were associated with lower intestinal fractional O2 extraction (0.61 ± 0.04 vs. 0.79 ± 0.02, P < 0.01) but preserved ΔPco2 (5 ± 2 vs. 25 ± 4 mmHg, P < 0.01). Therefore, alterations in O2 extraction in hemodilution seemed related to microvascular shunting, not to fast RBC velocity. The severe microvascular abnormalities suggest that normal ΔPco2 was not dependent on CO2 washout by the villi microcirculation. Increased perfusion in deeper intestinal layers might be an alternative explanation., (Copyright © 2016 the American Physiological Society.)

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.

Objective: To describe characteristics, outcomes and clinical presentations for hypertensive disease of pregnancy (HDP) in patients admitted to three ICUs in Argentina., Methods: Case-series multicenter study., Results: There were 184 patients with HDP. Mean age 26 ± 8; 90% did not present comorbidity; APACHEII 9[6-14]; SOFA24 2[1-4]; ICU-LOS 3[2-6] days and hospital-LOS 8[5-12] days. Gestational age 34 ± 5 weeks; 46% (85) nulliparous and 71% received routine prenatal care. Maternal mortality 3.3% (6) - 50% attributed to intracranial hemorrhage (ICH). Neonatal mortality 13.6%. Diagnostic categories: eclampsia (64; 35%), severe preeclampsia (60; 32.6%), HELLP (33; 17.9%), eclampsia-HELLP (18; 9.8%) and other (chronic/gestational-hypertension) (9: 4.7%). Severe hypertension in 46%, multiple organ dysfunction in 23%, acute respiratory distress in 8.7% and acute renal failure in 8%. Variables independently associated with eclampsia: maternal age (OR 1.07 [1.02-1.13], gestational age (OR 1.14 [1.04-1.24]) and nulliparity (OR 2.40 [1.19-4.85])., Conclusions: Although patients were young and the majority received appropriate prenatal care, they spent considerable time in hospital and presented severe morbidity. Maternal mortality was 3.3% and in half of these cases it was attributed to ICH. Eclampsia and severe preeclampsia represented two thirds of the diagnostic categories. Variables independently associated with eclampsia were maternal and gestational ages and nulliparity.

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.

Purpose: In Argentina, uninsured patients receive public health care, and the insured receive private health care. Our aim was to compare different outcomes between critically ill obstetric patients from both sectors., Methods: This is a prospective cohort, including pregnant/postpartum patients requiring admission to 1 intensive care unit in the public sector (uninsured) and 1 in the private (insured) from January 1, 2008, to September 30, 2011., Results: A total of 151 patients were included in the study. In uninsured (n = 63) vs insured (n = 88) patients, Acute Physiology and Chronic Evaluation II (APACHE II) and Sequential Organ Failure Assessment scores were 11 ± 6.5 vs 8 ± 4 and 3 (2-7) vs 1 (0-2), respectively, and 84% vs 100% received prenatal care (P = .001 for all). Multiple organ dysfunction syndrome (MODS) was present in 32 (54%) uninsured vs 9 (10%) insured patients (P = .001), and acute respiratory distress syndrome developed in 18 (30.5%) of 59 vs 2(2%) of 88 (P = .001). Neonatal survival was 80% vs 96% (P = .003). Variables independently associated with the development of MODS were APACHE II (odds ratio, 1.30 [1.13-1.49]), referral from another hospital (odds ratio, 11.43 [1.86-70.20]), lack of health insurance (odds ratio 6.75 [2.17-20.09]), and shock (odds ratio 4.82 [1.54-15.06]). Three patients died, all uninsured., Conclusions: Uninsured critically ill obstetric patients (public sector) were more severely ill on admission and experienced worse outcomes than insured patients (private sector). Variables independently associated with MODS were APACHE II, shock, referral from another hospital, and lack of insurance., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Worldwide, hypertensive disease of pregnancy is one of the most frequent causes of admission of obstetric patients to the ICU. Maternal mortality risk related to Hypertension during pregnancy in Latin America is significantly higher than in developed countries., Objectives: To describe the characteristics and outcomes of pregnant-postpartum patients with hypertensive disease of pregnancy admitted to ICU METHODS:, Design: Multicenter case series study., Population: pregnant-postpartum (<42days) patients with hypertensive disease of pregnancy admitted to ICU., Setting: 3 ICUs in Argentina, 2 from the Public (P1) and 1 from the Private Health Sector (P2)., Statistics: Continuous data are presented as mean±SD or median [IQR], and categorical data as number (%). Comparisons among continuous data were performed with unpaired t test or Mann-Whitney U test. Categorical variables were analyzed by Chi-square test or Fisher exact test as appropriate. A two-sided α<0.05 was considered as significant. SPSS version 15 was used., Results: One hundred and eighty four patients were included, 161(87.5%) from P1. General characteristics are shown in the Table. Gestational age was 34±5 weeks. Risk factors for preeclampsia not included in Charlson score were chronic hypertension (22;12%), Obesity (6;3%) and preeclampsia in previous pregnancy (5;3%). ICU admission was postpartum in 80%(145). Causes of admission were eclampsia (63;34%), severe preeclampsia (61;33%), HELLP (33;18%), Eclampsia-HELLP (18;10%), Chronic Hypertension (5;3%) and Gestational Hypertension (4;2%). Predictive mortality according with APACHEII was 14%. Antenatal care was present in 115/142(81%) patients; 97/124(78%) in P1 vs 18/18 (100%) in P2; p0.024. Antenatal care was appropriate in 77/108(71.3%) of patients; 59/90(65.5%) in P1 vs 18/18(100%) in P2; p0.001. Maternal deaths (6) occurred in the Public sector and none of the patients had received antenatal care. Causes of mortality were hemorrhagic stroke (3) and multiple organ dysfunction (3) Table 1., Conclusion: Most patients were from the public health sector and the majority did not have any comorbidity according with the Charlson score. Nevertheless, 18% presented risk factors for preeclampsia, not included in the mentioned score. Two-thirds of patients were admitted with eclampsia and severe preeclampsia. APACHEII overpredicted mortality. Half of deaths were related with hemorrhagic stroke, complication almost eradicated from developed countries. None of the patients who died had received antenatal care., (Copyright © 2012. Published by Elsevier B.V.)

Objective: To evaluate the effects of nitroglycerin (glyceryl trinitrate) on intestinal microcirculation during endotoxaemic shock., Design: Controlled experimental study., Setting: Research laboratory., Subjects: 20 anaesthetised, mechanically ventilated sheep., Interventions: Septic shock was induced by endotoxin infusion. After 60 minutes without resuscitation, sheep received fluid resuscitation and were randomised to control or nitroglycerin groups. Nitroglycerin was infused at a rate of 0.2 µg/kg/min for 90 minutes., Main Outcome Measure: Improved villi microcirculation., Results: Endotoxin lowered arterial blood pressure, cardiac output and intestinal blood flow, which were improved by fluid resuscitation. Mean (SD) ileal intramucosal-arterial PCO2 gradient increased during shock and remained elevated after resuscitation in control and nitroglycerin groups (8 [8], 15 [9] and 17 [9], and 6 [6], 13 [11] and 14 [9]mmHg, respectively; P < 0.05, baseline v shock and resuscitation for both groups). Villi microvascular flow index was reduced during shock and remained lower than baseline after the resuscitation in both groups (3.0 [0.0], 2.5 [0.2] and 2.7 [0.2], and 3.0 [0.0], 2.3 [0.3] and 2.6 [0.3], respectively; P < 0.05, baseline v shock and resuscitation for both groups). The red blood cell velocity behaved similarly (859 [443], 553 [236] and 670 [276], and 886 [440], 447 [124] and 606 [235] µm/s, respectively; P < 0.05, baseline v shock and resuscitation for both groups)., Conclusions: In endotoxaemic sheep, low doses of nitroglycerin failed to improve the subtle but persistent villi hypoperfusion that remains present after fluid resuscitation.

Objective: To compare systemic hemodynamics with microcirculatory changes at different vascular beds during progressive hemorrhage., Setting: University-based research laboratory., Subjects: Twelve anesthetized, mechanically ventilated sheep., Interventions: Sheep were randomly assigned to HEMORRHAGE or CONTROL group. In the HEMORRHAGE group (n = 8), three stepwise bleedings of 5 ml/kg at 30-min intervals were performed to add up 15 ml/kg. In the CONTROL group (n = 4), sheep had the same surgical preparation but were not bled., Measurements and Main Results: Progressive bleeding decreased cardiac output, and superior mesenteric artery blood flow, and systemic and intestinal oxygen transports from the first step of bleeding whereas systemic and intestinal oxygen consumption remained unchanged. Mean arterial blood pressure, arterial pH and base excess, and intramucosal-arterial PCO(2) were only significantly modified in the last step of bleeding. Arterial lactate increased and sublingual, and intestinal serosal and mucosal capillary microvascular flow indexes and red blood cell velocities progressively decreased after the first step of bleeding (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 1,082 +/- 29 vs. 977 +/- 79, 1,042 +/- 24 vs. 953 +/- 60, 287 +/- 65 vs. 262 +/- 16 mum/s; P < 0.05 for all)., Conclusions: Alterations in sublingual, intestinal microcirculation, and arterial lactate simultaneously arose from the first step of bleeding. The microcirculatory changes were identified either by semi-quantitative flow index or by quantitative red blood cell velocity measurements.

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 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., 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 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)., 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.

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.

Objective: To test the hypothesis that levosimendan increases systemic and intestinal oxygen delivery (DO(2)) and prevents intramucosal acidosis in septic shock., Design: Prospective, controlled experimental study., Setting: University-based research laboratory., Subjects: Nineteen anesthetized, mechanically ventilated sheep., Interventions: Endotoxin-treated sheep were randomly assigned to three groups: control (n=7), dobutamine (10 microg/kg/min, n=6) and levosimendan (100 microg/kg over 10 min followed by 100 microg/kg/h, n=6) and treated for 120 min., Measurements and Main Results: After endotoxin administration, systemic and intestinal DO(2) 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 PCO(2) difference (DeltaPCO(2)) 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 DO(2) was preserved in the dobutamine-treated group (22.3+/-4.7 vs 26.8+/-7.0 ml/min/kg, p=NS) but intestinal DO(2) decreased (98.9+/-0.2 vs 68.0+/-22.9 ml/min/kg, p<0.05) and DeltaPCO(2) increased (12+/-5 vs 25+/-11 mmHg, p<0.05). The administration of levosimendan prevented declines in systemic and intestinal DO(2) (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 DeltaPCO(2) (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)., Conclusions: Compared with dobutamine, levosimendan increased intestinal blood flow and diminished intramucosal acidosis in this experimental model of sepsis.

Objectives: Levosimendan is an inotropic and vasodilator drug that has proved to be useful in cardiogenic shock. Pretreatment with levosimendan in experimental hypodynamic septic shock in pigs has shown valuable effects in oxygen transport. Our goal was to assess the effects of levosimendan in a normodynamic model of endotoxaemia., Methods: Twelve sheep were anaesthetized and mechanically ventilated. After taking basal haemodynamic and oxygen transport measurements, sheep were assigned to two groups during 120 min: (1) endotoxin (5 microg/kg endotoxin); (2) levosimendan (5 microg/kg endotoxin plus levosimendan 200 microg/kg followed by 200 microg/kg/h). Both groups received hydration of 20 ml/kg/h of saline solution., Results: In the endotoxin group, cardiac output, intestinal blood flow and systemic and intestinal oxygen transports and consumptions (DO(2) and VO(2)) remained unchanged. In the levosimendan group, systemic and intestinal DO(2) were significantly higher than in the endotoxin group. Because stroke volume did not change (basal versus 120': 0.9+/-0.1 ml/kg versus 0.9+/-0.2 ml/kg, p=0.3749), the elevation in cardiac output by levosimendan (145+/-17 ml/min/kg versus 198+/-16 ml/min/kg, p=0.0096) was related to an increased heart rate (159+/-32 beats l/min versus 216+/-19 beats l/min, p=0.0037). Levosimendan precluded the development of gut intramucosal acidosis at 120' (endotoxin versus levosimendan, ileal intramucosal-arterial PCO(2) difference: 19+/-4 Torr versus 10+/-4 Torr, p=0.0025). However, levosimendan decreased mean arterial blood pressure (99+/-20 Torr versus 63+/-13 Torr, p=0.0235) and increased blood lactate levels (2.4+/-0.9 mmol/l versus 4.8+/-1.5 mmol/l, p=0.0479). All p-values are differences in specific points (paired or unpaired t-test with Bonferroni correction) after two-way repeated measures ANOVA. A p-value<0.05 was considered significant., Conclusions: Levosimendan improved oxygen transport and prevented the development of intramucosal acidosis in this experimental model of endotoxaemia. However, systemic hypotension and lactic acidosis occurred. Additional studies are needed to show if different doses and timing of levosimendan administration in septic shock might improve gut perfusion without adverse effects.

Introduction: Our 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., Methods: We 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., Results: Ninety-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., Conclusion: CCI 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.

Introduction: Continuous monitoring of bladder partial carbon dioxide tension (PCO2) using fibreoptic sensor technology may represent a useful means by which tissue perfusion may be monitored. In addition, its changes might parallel tonometric gut PCO2. Our hypothesis was that bladder PCO2, measured using saline tonometry, will be similar to ileal PCO2 during ischaemia and reperfusion., Method: Six anaesthetized and mechanically ventilated sheep were bled to a mean arterial blood pressure of 40 mmHg for 30 min (ischaemia). Then, blood was reinfused and measurements were repeated at 30 and 60 min (reperfusion). We measured systemic and gut oxygen delivery and consumption, lactate and various PCO2 gradients (urinary bladder-arterial, ileal-arterial, mixed venous-arterial and mesenteric venous-arterial). Both bladder and ileal PCO2 were measured using saline tonometry., Results: After bleeding systemic and intestinal oxygen supply dependency and lactic acidosis ensued, along with elevations in PCO2 gradients when compared with baseline values (all values in mmHg; bladder DeltaPCO2 3 +/- 3 versus 12 +/- 5, ileal DeltaPCO2 9 +/- 5 versus 29 +/- 16, mixed venous-arterial PCO2 5 +/- 1 versus 13 +/- 4, and mesenteric venous-arterial PCO2 4 +/- 2 versus 14 +/- 4; P < 0.05 versus basal for all). After blood reinfusion, PCO2 gradients returned to basal values except for bladder DeltaPCO2, which remained at ischaemic levels (13 +/- 7 mmHg)., Conclusion: Tissue and venous hypercapnia are ubiquitous events during low flow states. Tonometric bladder PCO2 might be a useful indicator of tissue hypoperfusion. In addition, the observed persistence of bladder hypercapnia after blood reinfusion may identify a territory that is more susceptible to reperfusion injury. The greatest increase in PCO2 gradients occurred in gut mucosa. Moreover, the fact that ileal DeltaPCO2 was greater than the mesenteric venous-arterial PCO2 suggests that tonometrically measured PCO2 reflects mucosal rather than transmural PCO2. Ileal DeltaPCO2 appears to be the more sensitive marker of ischaemia.

Objective: To assess renal dysfunction and outcome in patients treated exclusively with colistin vs. other antibiotics., Design and Setting: Prospective cohort study in a mixed ICU in a university-affiliated hospital., Patients: 185 patients infected with Acinetobacter baumannii and Pseudomonas aeruginosa after an ICU stay longer than 48 h: 55 in the colistin group and 130 in the noncolistin group, similar in age, APACHE II, medical status, and SOFA score., Measurements and Results: We recorded data on epidemiology and severity of illness, site of infection, renal function before and after treatment, clinical cure, and mortality. Clinical cure was defined as simultaneous normalization of central temperature (< or = 38 degrees), leukocyte count (< or = 10,000/mm3), and PaO2/FIO2 ratio (>187). Before treatment creatinine was 0.9+/-0.2 in the colistin group and 0.9+/-0.1 in the noncolistin group; after treatment the value was 1.0+/-0.3 in both groups. The most frequent infection was ventilator-associated pneumonia: 53% vs. 66% in colistin and noncolistin groups, respectively, Acinetobacter was the cause in 65% and 60% and Pseudomonas in 35% and 53%. In the noncolistin group 81% of patients were treated with carbapenems. Inadequate empirical antimicrobial treatment was more frequent in the colistin group (100% vs. 8%), but there were no differences in the frequency of clinical cure on day 6 of treatment (15% and 17%) or in mortality (29% and 24%)., Conclusions: Colistin appears to be as safe and as effective as other antimicrobials for treatment of sepsis caused by Acinetobacter and Pseudomonas in critically ill patients.

Introduction: Increased intramucosal-arterial carbon dioxide tension (PCO2) difference (DeltaPCO2) is common in experimental endotoxemia. However, its meaning remains controversial because it has been ascribed to hypoperfusion of intestinal villi or to cytopathic hypoxia. Our hypothesis was that increased blood flow could prevent the increase in DeltaPCO2., Methods: In 19 anesthetized and mechanically ventilated sheep, we measured cardiac output, superior mesenteric blood flow, lactate, gases, hemoglobin and oxygen saturations in arterial, mixed venous and mesenteric venous blood, and ileal intramucosal PCO2 by saline tonometry. Intestinal oxygen transport and consumption were calculated. After basal measurements, sheep were assigned to the following groups, for 120 min: (1) sham (n = 6), (2) normal blood flow (n = 7) and (3) increased blood flow (n = 6). Escherichia coli lipopolysaccharide (5 microg/kg) was injected in the last two groups. Saline solution was used to maintain blood flood at basal levels in the sham and normal blood flow groups, or to increase it to about 50% of basal in the increased blood flow group., Results: In the normal blood flow group, systemic and intestinal oxygen transport and consumption were preserved, but DeltaPCO2 increased (basal versus 120 min endotoxemia, 7 +/- 4 versus 19 +/- 4 mmHg; P < 0.001) and metabolic acidosis with a high anion gap ensued (arterial pH 7.39 versus 7.35; anion gap 15 +/- 3 versus 18 +/- 2 mmol/l; P < 0.001 for both). Increased blood flow prevented the elevation in DeltaPCO2 (5 +/- 7 versus 9 +/- 6 mmHg; P = not significant). However, anion-gap metabolic acidosis was deeper (7.42 versus 7.25; 16 +/- 3 versus 22 +/- 3 mmol/l; P < 0.001 for both)., Conclusions: In this model of endotoxemia, intramucosal acidosis was corrected by increased blood flow and so might follow tissue hypoperfusion. In contrast, anion-gap metabolic acidosis was left uncorrected and even worsened with aggressive volume expansion. These results point to different mechanisms generating both alterations.

Background: An increase in intramucosal-arterial Pco2 gradient (DeltaPco2) might be caused by tissue hypoxia or by diminished blood flow. Our hypothesis was that DeltaPco2 should not be altered in anemic hypoxia with preserved blood flow., Methods: In 18 anesthetized, mechanically ventilated sheep, oxygen transport was stepwise reduced by hemorrhage (hypovolemia, n = 9) or by hemorrhage and simultaneous dextran infusion (hemodilution, n = 9)., Results: Hypovolemia and hemodilution produced comparable decreases in systemic and intestinal oxygen transport and uptake. However, mixed venoarterial and mesenteric venoarterial Pco2 gradients and DeltaPco2 were significantly higher in hypovolemia than in hemodilution (25 +/- 5 vs. 10 +/- 2 mm Hg; 21 +/- 6 vs. 10 +/- 5 mm Hg; and 41 +/- 18 vs. 14 +/- 9 mm Hg, respectively; p < 0.01)., Conclusion: DeltaPco2 did not reflect intestinal dysoxia during Vo2/Do2 dependency attributable to hemodilution. Blood flow seems to be the main determinant of DeltaPco2.

Objective: We examined whether PEEP during the first hours of ARDS can induce such a change in oxygenation that could mask fulfillment of the AECC criteria of a PaO(2)/FIO(2)