Diego Orbegozo

Effects of Different Crystalloid Solutions on Hemodynamics, Peripheral Perfusion, and the Microcirculation in Experimental Abdominal Sepsis.

Background:Crystalloid solutions are used to restore intravascular volume in septic patients, but each solution has limitations. The authors compared the effects of three crystalloid solutions on hemodynamics, organ function, microcirculation, and survival in a sepsis model. Methods:Peritonitis was induced by injection of autologous feces in 21 anesthetized, mechanically ventilated adult sheep. After baseline measurements, animals were randomized to lactated Ringer’s (LR), normal saline (NS), or PlasmaLyte as resuscitation fluid. The sublingual microcirculation was assessed using sidestream dark field videomicroscopy and muscle tissue oxygen saturation with near-infrared spectroscopy. Results:NS administration was associated with hyperchloremic acidosis. NS-treated animals had lower cardiac index and left ventricular stroke work index than LR-treated animals from 8 h and lower mean arterial pressure than LR-treated animals from 12 h. NS-treated animals had a lower proportion of perfused vessels than LR-treated animals after 12 h (median, 82 [71 to 83] vs. 85 [82 to 89], P = 0.04) and greater heterogeneity of proportion of perfused vessels than PlasmaLyte or LR groups at 18 h. Muscle tissue oxygen saturation was lower at 16 h in the NS group than in the other groups. The survival time of NS-treated animals was shorter than that of the LR group (17 [14 to 20] vs. 26 [23 to 29] h, P < 0.01) but similar to that of the PlasmaLyte group (20 [12 to 28] h, P = 0.74). Conclusions:In this abdominal sepsis model, resuscitation with NS was associated with hyperchloremic acidosis, greater hemodynamic instability, a more altered microcirculation, and more severe organ dysfunction than with balanced fluids. Survival time was shorter than in the LR group.

Modulation of Dietary Lipid Composition During Acute Respiratory Distress Syndrome Systematic Review and Meta-Analysis

BACKGROUND Pharmaconutrition including omega-3 and competitive analogs of omega-6 fatty acids has been used to modulate the inflammatory response during acute respiratory distress syndrome (ARDS). The clinical benefit of this approach when assessed in prospective randomized clinical trials has been inconsistent. We tried to assess the reasons for the conflicting results, including the possible influence of the composition of the control solution. METHODS We collected data from studies listed in PubMed, Ovid, the Cochrane Database of Systematic Reviews, Embase, the U.S. National Institute of Health database, and the ARDSnet database up to March 2013. We included all trials that evaluated effects of enteral pharmaconutrition vs a control solution on mortality, ventilator-free days, length of stay (LOS) in the intensive care unit (ICU), and ICU-free days. A sensitivity analysis was carried out to study the influence of the lipid content of the control solution. RESULTS We found 7 eligible studies (802 patients; 405 randomized to pharmaconutrition). The aggregated results showed no overall effect on mortality (risk ratio [RR] = 0.83 [0.55-1.25], P = .37), but there was a mortality benefit when only studies in which pharmaconutrition was compared to a lipid-rich control solution were considered (RR = 0.57 [0.41-0.78], P < .001). ICU LOS was shorter in patients randomized to pharmaconutrition (RR = 0.5 [0.85-0.16]). CONCLUSION Use of enteral pharmaconutrition in patients with ARDS was associated with decreased mortality only when the comparator solution contained a greater amount of lipid than is currently recommended. Hence, there is insufficient evidence to support the use of enteral pharmaconutrition in ARDS.

The harmful effects of hypertonic sodium lactate administration in hyperdynamic septic shock

ABSTRACT Hypertonic sodium lactate (HTL) expands intravascular volume and may provide an alternative substrate for cellular metabolism in sepsis. We compared the effects of HTL, hypertonic saline (HTS), 0.9% (“normal”) saline (NS) and Ringers lactate (RL) on hemodynamics, sublingual and renal microcirculation, renal, mesenteric and brain perfusion, renal and cerebral metabolism, and survival in anesthetized, mechanically ventilated, adult female sheep. Animals (7 in each group) were randomized to receive a bolus (over 15-min) of 3 mL/kg 0.5 M HTL, 3 mL/kg 3% HTS, 10.8 mL/kg NS, or 10.8 mL/kg RL at 2, 6, and 10 h after induction of fecal peritonitis, followed by 2-h infusions of 1 mL/kg/h (HTL/HTS groups) or 3.6 mL/kg/h (NS/RL groups). Animals also received RL and hydroxyethyl starch (ratio 1:1) titrated to maintain pulmonary artery occlusion pressure at baseline levels throughout the experiment. Animals were observed until their spontaneous death. Fluid balance was lower in the HTL and HTS groups than in the other groups from 4 h. Hemodynamic variables were similar among groups during the first 12 h, but thereafter the HTL group had more pronounced decreases in blood pressure and cardiac function. Sublingual and renal microcirculatory abnormalities occurred earlier in the HTL group. Kidney and brain perfusion decreased more rapidly in the HTL group. Median survival times were significantly shorter in the HTL (17 h) and NS (16 h) groups than in the HTS (22 h) or RL (20 h) groups (P = 0.0029). In conclusion, in an ovine model of septic shock, administration of HTL was associated with earlier onset impaired tissue perfusion and shorter survival time. These observations raise concerns about use of HTL in septic shock.

Oral Nitrate Increases Microvascular Reactivity and the Number of Visible Perfused Microvessels in Healthy Volunteers

Nitric oxide (NO) plays an important role in controlling microcirculatory function, but the effects of exogenous administration of nitrate (NO3-) on the microcirculation have not been well studied. We evaluated whether NO3- could influence the microvascular response to hypoxia in 17 healthy volunteers. We used a vascular occlusion test (VOT) to assess the response of near-infrared spectroscopy-derived indexes to hypoxic stress before and 2 h 15 min after oral administration of 800 mg potassium nitrate. We also monitored changes in the sublingual microcirculation using side-stream dark-field (SDF) video microscopy. The descending (7.3 [6.8-8.1] to 8.2 [7.9-9.8] %/min, p = 0.01) and ascending (201 [180-233] to 240 [197-285] %/min, p = 0.01) thenar oxygen saturation (StO2) slopes were significantly greater during VOT after nitrate administration than before. Sublingual SDF measurements showed increases in the total number of visible perfused vessels (i.e., from 14.1 [13.2-15.5] to 16.3 [15.4-16.7] vessels/mm, p < 0.01) and in the number of visible perfused small vessels (i.e., from 12.2 [11.5-13.7] to 14.2 [13.5-15.3] vessels/mm, p < 0.01) after nitrate administration but no changes in the microvascular flow index or in the proportion of visible perfused vessels, which were already maximal at baseline. Oral administration of nitrate therefore significantly influenced the response to a hypoxic challenge, increasing the number of visible perfused vessels and thus possibly limiting the O2 diffusion distance.

970: USE OF A BIOMARKER SCORE IN PATIENTS WITH ACUTE RESPIRATORY DISTRESS SYNDROME

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) expression in many diseases, though the contribution of miRNAs to the pathophysiology of ALI remains obscure. We hypothesized that in ALI, dysregulated miRNAs modulate gene targets that control endothelial permeability leading to impaired barrier function. Methods: 8-week-old C57BL/6 mice were treated with intratracheal bleomycin or PBS. Lungs were collected at 4 or 7 days. miRNA expression was compared using a qPCR based 56-miRNA array. TargetScan and Enrichr were used to identify predicted gene targets and biological processes of 4 highly down-regulated miRNAs. Expression of 4 predicted miR-26a gene targets, EphA2, VEGFC, KDR and ROCK1 was evaluated by qPCR. EphA2 protein levels were measured by western blot analysis. In situ hybridization was performed to localize lung miR-26a. Human lung microvascular endothelial cells (HMVEC-L) were transfected with miR-26a mimic, inhibitor and negative controls. miR-26a, EphA2 mRNA/protein and cell permeability were measured. Results: Bleomycin decreased 4 miRNAs (miR-1, miR-26a, miR-30b and miR-30c) by greater than 6 fold. Of these miRNAs, miR-26a is predicted to regulate 135 genes involved in cell adhesion and relevant to ALI, including EphA2, VEGFC, KDR and ROCK1. Only lung EphA2 mRNA and protein significantly increased (1.7 fold and 1.5 fold) at 7 days. Transfection of HMEVC-L with miR-26a mimic significantly decreased EphA2 mRNA and protein (0.5 fold) and miR-26a inhibitor significantly increased EphA2 mRNA and protein (1.3 fold). Transfection with miR-26a inhibitor significantly increased HMVEC-L permeability at baseline and with VEGF stimulation, while transfection with miR-26a mimic had no impact. Conclusions: Multiple miRNAs are decreased in bleomycin-induced ALI. miR-26a, a putative regulator of genes involved in cell adhesion, regulated EphA2 expression and endothelial permeability in vitro. Future studies will interrogate targeted delivery systems for miRNA mimics and inhibitors as a novel therapeutic strategy.