Red Cell Distribution Width After Subarachnoid Hemorrhage.

BACKGROUND: High red cell distribution width (RDW) values have been associated with increased hospital mortality in critically ill patients, but few data are available for subarachnoid hemorrhage (SAH). METHODS: We analyzed an institutional database of adult (>18 y) patients admitted to the Department of Intensive Care after nontraumatic SAH between January 2011 and May 2016. RDW (normal value, 10.9% to 13.4%) was obtained daily from admission for a maximum of 7 days, from routine blood analysis. We recorded the occurrence of delayed cerebral ischemia (DCI), and neurological outcome (assessed using the Glasgow Outcome Scale [GOS]) at 3 months. RESULTS: A total of 270 patients were included (median age 54 y-121/270 male [45%]), of whom 96 (36%) developed DCI and 109 (40%) had an unfavorable neurological outcome (GOS, 1 to 3). The median RDW on admission was 13.8 [13.3 to 14.5]% and the highest value during the intensive care unit (ICU) stay 14.2 [13.6 to 14.8]%. The RDW was high (>13.4%) in 177 patients (66%) on admission and in 217 (80%) at any time during the ICU stay. Patients with a high RDW on admission were more likely to have an unfavorable neurological outcome. In multivariable regression analysis, older age, a high WFNS grade on admission, presence of DCI or intracranial hypertension, previous neurological disease, vasopressor therapy and a high RDW (OR, 1.1618 [95% CI, 1.213-2.158]; P=0.001) during the ICU stay were independent predictors of unfavorable neurological outcome. CONCLUSIONS: High RDW values were more likely to result in an unfavorable outcome after SAH. This information could help in the stratification of SAH patients already on ICU admission.

Echocardiography and passive leg raising in the postoperative period: A prospective observational study.

BACKGROUND: Signs of hypovolaemia are frequent in the postoperative period, but not all patients need or respond to fluid administration. An increase in cardiac output (CO) after passive leg raising (PLR) has been demonstrated to be useful as a volume response predictor in non-surgical, spontaneously breathing patients. OBJECTIVE: The objective of this study was to evaluate the accuracy of transthoracic echocardiography after PLR to predict fluid responsiveness in post-surgical patients. DESIGN: A prospective observational study. SETTING: A tertiary hospital between January and July 2015. PATIENTS: Fifty-one spontaneously breathing postoperative patients with suspected hypovolaemia (arterial hypotension, oliguria, tachycardia or delayed capillary refill) were considered for the study. INTERVENTION: Demographic and personal data were collected, as well as heart rate variations, mean arterial pressure during PLR and after administering 500 ml of Ringer's lactate solution. CO was measured by transthoracic echocardiography. MAIN OUTCOME MEASURES: The primary outcome was measurement of CO before and after PLR and Ringer's lactate administration. RESULTS: Forty-one patients were included in the study (six patients were excluded because of a poor echocardiographic window and four because of misalignment of the Doppler and outflow tract of the left ventricle). Twenty-two patients (54%) were considered responders to fluid therapy, with an increase of stroke volume greater than or equal to 15% after 500 ml lactated Ringer's infusion. The highest area under the curve was found for an increase in CO (0.91 ±â€Š0.05; 95% confidence interval 0.78 to 0.97). An increase in CO greater than 11% after the PLR manoeuvre predicts a volume response with 68% sensitivity and 100% specificity. CONCLUSION: This is the first study showing that measurement of CO after PLR can predict volume response in spontaneously breathing postoperative patients.

Altered liver function in patients undergoing veno-arterial extracorporeal membrane oxygenation (ECMO) therapy.

BACKGROUND: Multiple organ dysfunction can occur in patients undergoing Veno-arterial Extra Corporal Membrane Oxygenation (VA-ECMO); however, liver function has not been well studied in this setting. METHODS: In a review of our institutional ECMO database (n=162), we collected aspartate (AST) and alanine (ALT) transaminases, total bilirubin and international normalized ratio (INR) at time of ECMO initiation (baseline) and once daily during therapy in patients who survived for at least 24 hours. Elevated liver enzymes (ELE) were defined if AST and/or ALT were > 200 UI/L, and acute liver failure (ALF) as the presence of an INR ≥ 1.5, new onset encephalopathy and an elevated total bilirubin concentrations. RESULTS: On a total of 80 patients undergoing VA-ECMO, 69 patients met the inclusion criteria (cardiogenic shock, n=52; refractory cardiac arrest, n=15; cardiac failure following severe ARDS, n=2). Of them, 45 (65%) had early ELE after ECMO initiation (median highest AST and ALT were 528 [251-2606] UI/L and 513 [130-1031] UI/L, respectively). Two thirds of patients with ELE (N = 30) had a progressive reduction in AST and ALT, but the levels were normalized only after 5 [5-6] days. Among patients with ELE, 21/45 (47%) had AST and/or ALT levels above > 1000 UI/L. A total of 14/69 (20%) patients developed ALF. However, mortality rate was not significantly higher in patients with ELE or ALF when compared to others. CONCLUSIONS: A substantial proportion of patients needing VA-ECMO have early ELE, which usually improves over days. The prognostic implications are not evident.

Red blood cell transfusion strategies in critically ill patients: lessons from recent randomized clinical studies.

A randomized, multicenter trial conducted in 32 northern European general intensive care units (ICUs) enrolled some patients with septic shock randomly assigned to receive a red blood cell transfusion when the hemoglobin (Hb) level was ≤7 g/dL ("lower threshold"; N.=502) or ≤9 g/dL ("higher threshold"; N.=496) throughout the ICU stay. Patients were excluded if they had an acute coronary syndrome, life-threatening bleeding, acute burn injury, had already been transfused or had previously experienced transfusion-related reactions. The two groups of patients had comparable severity of disease scores and chronic cardiovascular conditions. Median Hb values were 7.7 g/dL in the lower and 9.3 g/dL in the higher threshold groups and these values remained stable during the study period. There was no significant difference in 90-day mortality (primary end-point) between the two groups (216/502, 43.0% in the lower vs. 223/496, 45.0% in the higher group, RR 0.94 [95% CI: 0.78-1.09; P=0.44]), even after adjustment for several confounders. In the higher threshold group, approximately twice as many transfusions were given (3088 vs. 1545 units transfused, P<0.001) as in the lower threshold group. In the lower threshold group, more patients received no RBC transfusion (36% vs. 1.2%, P<0.001) than in the higher threshold group, but there were also more temporary protocol suspensions (5.9 % vs. 2.2%, P=0.004), in particular because of myocardial ischemia (6/488, 1.2% vs. 0/489), life-threatening bleeding (18/488, 3.7% vs. 9/489, 1.8%) and need for higher Hb levels during extracorporeal membrane oxygenation therapy. We discuss how anemia should be managed in patients with sepsis or other critical illness, especially in the context of the potential risks associated with RBC transfusion and data from other recent large randomized trials.

Role of selective V1a receptor agonism in ovine septic shock.

OBJECTIVE: The vasopressor effect of arginine vasopressin, a mixed V1a/V2 receptor (V1aR/V2R) agonist, is mediated through the V1aR. Because V2R stimulation may aggravate sepsis-induced vasodilation, fluid accumulation, and microvascular thrombosis, a higher V1aR vs. V2R selectivity might be advantageous. The objective of this study was to elucidate the effects of a first-line therapy with the selective V1aR agonist Phe2-Orn8-Vasotocin vs. arginine vasopressin or norepinephrine on cardiopulmonary hemodynamics and organ function in ovine septic shock. DESIGN: Randomized controlled laboratory experiment. SETTING: University animal research facility. SUBJECTS: : Twenty-four chronically instrumented sheep. INTERVENTIONS: After the onset of fecal peritonitis-induced septic shock (mean arterial pressure <60 mm Hg), sheep were randomly assigned to receive first-line treatment with Phe2-Orn8-Vasotocin (0.05 µg·kg·h), arginine vasopressin (0.05 µg·kg·h), or normal saline (each n = 8). In all groups, open-label norepinephrine was additionally titrated up to 1 µg·kg·min to maintain mean arterial pressure at 70 ± 5 mm Hg, if necessary. MEASUREMENTS AND MAIN RESULTS: Compared with single norepinephrine therapy, the selective V1aR agonist Phe2-Orn8-Vasotocin reduced norepinephrine requirements (2-6 hrs: p < .05 each) and fluid accumulation (p = .043). In addition, mean arterial pressure (6-10 hrs: p < .05 each), pulmonary gas exchange (8-10 hrs: p < .05 each), and global oxygen transport (10 hrs: p < .05 each) were improved by Phe2-Orn8-Vasotocin vs. both other groups. Despite similar preload left ventricular stroke work index was higher in Phe2-Orn8-Vasotocin- than in arginine vasopressin-treated animals (10 hrs: p = .02). Metabolic dysfunction (base excess, lactate concentrations) and renal dysfunction (urinary output, creatinine clearance) were attenuated by Phe2-Orn8-Vasotocin infusion when compared with arginine vasopressin and single norepinephrine therapy. Immunohistochemical analyses of lung tissue revealed higher hemeoxygenase-1 and lower 3-nitrotyrosine concentrations in Phe2-Orn8-Vasotocin-treated animals vs. both other groups (p < .05 each). In addition, the selective V1aR agonist Phe2-Orn8-Vasotocin slightly prolonged survival when compared with arginine vasopressin (p = .01) and standard treatment with norepinephrine (p = .003). CONCLUSIONS: Selective V1aR agonism appears to be superior to the V1aR/V2R agonist arginine vasopressin and single norepinephrine infusion for hemodynamic support in septic shock.

Effects of combined arginine vasopressin and levosimendan on organ function in ovine septic shock.

OBJECTIVE: To compare the effects of a first-line therapy of combined arginine vasopressin, levosimendan, and norepinephrine with arginine vasopressin + norepinephrine or norepinephrine alone in ovine septic shock. DESIGN: Prospective, randomized, controlled laboratory experiment. SETTING: University animal research facility. SUBJECTS: Twenty-one chronically instrumented sheep. INTERVENTIONS: After the onset of fecal peritonitis-induced septic shock (mean arterial pressure <60 mm Hg), sheep were randomly assigned to receive first-line treatment with arginine vasopressin (0.5 mU·kg·min), combined arginine vasopressin (0.5 mU·kg·min) and levosimendan (0.2 µg·kg·min), or normal saline (each n = 7) for 24 hrs. In all groups, open-label norepinephrine was additionally titrated to maintain mean arterial pressure at 70 ± 5 mm Hg, if necessary. MEASUREMENTS AND MAIN RESULTS: Arginine vasopressin + levosimendan + norepinephrine improved left ventricular contractility (higher stroke work indices at similar or lower preload) and pulmonary function (Pao2/Fio2 ratio) when compared with the other groups (p < .05 each). Both nonadrenergic treatment strategies reduced open-label norepinephrine doses. However, only arginine vasopressin + levosimendan + norepinephrine limited fluid requirements and positive fluid balance vs. both other groups (p < .05 each). In addition, arginine vasopressin + levosimendan + norepinephrine increased mixed venous oxygen saturation as compared with arginine vasopressin + norepinephrine. Histologic tissue analyses and pulmonary hemeoxygenase-1 activity revealed no differences among groups. Notably, arginine vasopressin + levosimendan + norepinephrine therapy reduced pulmonary 3-nitrotyrosine levels (p = .028 vs. control animals) as well as urinary protein/creatinine ratio (p < .05 each) and slightly prolonged survival when compared with both other groups (4 hrs vs. arginine vasopressin + norepinephrine: p = .013; 7 hrs vs. norepinephrine alone: p = .003). CONCLUSIONS: First-line cardiovascular support with combined arginine vasopressin and levosimendan supplemented with norepinephrine improves myocardial, vascular, pulmonary, and renal function as compared with arginine vasopressin + norepinephrine in septic shock.