Systemic and microcirculatory effects of blood transfusion in experimental hemorrhagic shock.

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 PCO2 to arteriovenous oxygen content difference ratio (Pv-aCO2/Ca-vO2) 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 O2 and CO2 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 Pv-aCO2/Ca-vO2 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). Pv-aCO2/Ca-vO2 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, Pv-aCO2/Ca-vO2 was poorly correlated with respiratory quotient, and its physiologic behavior was different. Thus, it might be a misleading surrogate for anaerobic metabolism.

Hypertensive disease of pregnancy in the ICU: a multicenter study.

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.

Health insurance status and outcomes of critically ill obstetric patients: a prospective cohort study in Argentina.

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.

Failure of nitroglycerin (glyceryl trinitrate) to improve villi hypoperfusion in endotoxaemic shock in sheep.

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.

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.

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

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.

Urinary bladder partial carbon dioxide tension during hemorrhagic shock and reperfusion: an observational study.

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.

Safety and efficacy of colistin in Acinetobacter and Pseudomonas infections: a prospective cohort study.

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.

Increased blood flow prevents intramucosal acidosis in sheep endotoxemia: a controlled study.

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.

Intramucosal-arterial Pco2 gradient does not reflect intestinal dysoxia in anemic hypoxia.

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.

Impact of positive end-expiratory pressure on the definition of acute respiratory distress syndrome.

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)