Altered Microvascular Reactivity During a Skin Thermal Challenge Is Associated With Organ Dysfunction and Slow Recovery After Cardiac Surgery.

OBJECTIVES: To assess microvascular reactivity during a skin thermal challenge early post-cardiac surgery and its association with outcomes. DESIGN: Noninvasive physiological study. SETTING: Thirty-five-bed department of intensive care. PARTICIPANTS: Patients admitted to the intensive care unit post-cardiac surgery. INTERVENTIONS: Thermal challenge. MEASUREMENTS AND MAIN RESULTS: A total of 46 patients were included; 14 needed vasoactive or ventilatory support for at least 48 hours (slow recovery), and 32 had a more rapid recovery. Skin blood flow (SBF) was measured on the anterior proximal forearm using skin laser Doppler. A thermal challenge was performed by abruptly increasing local skin temperature from 37°C to 43°C while monitoring SBF. The ratio between SBFs at 43°C and 37°C was calculated to measure microvascular reactivity. SBF at 37°C was not significantly different in patients with a slow recovery and those with a rapid recovery, but SBF after 9 minutes at 43°C was lower (48.5 [17.3-69.0] v 85.1 [45.2-125.7], p < 0.01), resulting in a lower SBF ratio (2.8 [1.5-4.7] v 4.8 [3.7-7.8], p < 0.01). Patients with lower SBF ratios were more likely to have dysfunction of at least one organ (assessed using the sequential organ dysfunction score) 48 hours post-cardiac surgery than those with higher ratios: 88% versus 40% versus 27% (p < 0.01), respectively, for the lowest, middle, and highest tertiles of SBF ratio. In multivariable analysis, a lower SBF ratio was an independent risk factor for slow recovery. CONCLUSIONS: Early alterations in microvascular reactivity, evaluated by a skin thermal challenge, are correlated with organ dysfunction. These observations may help in the development of new, simple, noninvasive monitoring systems in postoperative patients.

Transfusion increased skin blood flow when initially low in volume-resuscitated patients without acute bleeding.

Background: Alterations in skin blood flow is a marker of inadequate tissue perfusion in critically ill patients after initial resuscitation. The effects of red blood cell transfusions (RBCT) on skin perfusion are not described in this setting. We evaluated the effects of red blood cell transfusions on skin tissue perfusion in critically ill patients without acute bleeding after initial resuscitation. Methods: A prospective observational study included 175 non-bleeding adult patients after fluid resuscitation requiring red blood cell transfusions. Using laser Doppler, we measured finger skin blood flow (SBF) at skin basal temperature (SBFBT), together with mean arterial pressure (MAP), heart rate (HR), hemoglobin (Hb), central venous pressure (CVP), lactate, and central or mixed venous oxygen saturation before and 1 h after RBCT. SBF responders were those with a 20% increase in SBFBT after RBCT. Results: Overall, SBFBT did not significantly change after RBCT [from 79.8 (4.3-479.4) to 83.4 (4.9-561.6); p = 0.67]. A relative increase equal to or more than 20% in SBFBT after RBCT (SBF responders) was observed in 77/175 of RBCT (44%). SBF responders had significantly lower SBFBT [41.3 (4.3-279.3) vs. 136.3 (6.5-479.4) perfusion units; p < 0.01], mixed or central venous oxygen saturation (62.5 ± 9.2 vs. 67.3% ± 12.0%; p < 0.01) and CVP (8.3 ± 5.1 vs. 10.3 ± 5.6 mmHg; p = 0.03) at baseline than non-responders. SBFBT increased in responders [from 41.3 (4.3-279.3) to 93.1 (9.8-561.6) perfusion units; p < 0.01], and decreased in the non-responders [from 136.3 (6.5-479.4) to 80.0 (4.9-540.8) perfusion units; p < 0.01] after RBCT. Pre-transfusion SBFBT was independently associated with a 20% increase in SBFBT after RBCT. Baseline SBFBT had an area under receiver operator characteristic of 0.73 (95% CI, 0.68-0.83) to predict SBFBT increase; A SBFBT of 73.0 perfusion units (PU) had a sensitivity of 71.4% and a specificity of 70.4% to predict SBFBT increase after RBCT. No significant differences in SBFBT were observed after RBCT in different subgroup analyses. Conclusion: The skin blood flow is globally unaltered by red blood cell transfusions in non-bleeding critically ill patients after initial resuscitation. However, a lower SBFBT at baseline was associated with a relative increase in skin tissue perfusion after RBCT.

An increase in skin blood flow induced by fluid challenge is associated with an increase in oxygen consumption in patients with circulatory shock.

PURPOSE: To investigate whether an increase in skin blood flow (SBF) after fluid challenge was associated with an increase in oxygen consumption (VO2) in patients with circulatory shock. MATERIALS AND METHODS: We studied 62 patients with shock who required fluid challenge. Using laser Doppler, we measured finger SBF at basal temperature (SBFBT) and after a thermal challenge test (SBFTCT), before and after a fluid challenge (500 ml of Plasmalyte®). In fluid responders (i.e., increase in cardiac index ≥15%), VO2 responders (VO2R) were those with a ≥15% increase in VO2. RESULTS: Of the 62 patients, 33 were fluid responders and 16 of these were VO2R. At baseline, VO2R had lower SBFBT (21[14-52] vs 83[24-116] PU, p = 0.03) and SBFTCT (2.1[1.2-3.3] vs 4.4[2.2-5.6] PU/°C, p = 0.02) than VO2 non-responders (VO2NR); hemodynamic variables were not significantly different. The increase in SBFBT (∆SBFBT) after fluid challenge was greater in VO2R than in VO2NR (141[83-174] vs 57[17-150]%, p = 0.03). Areas under the curves for baseline SBFTCT (0.83 ± 0.07 [0.68-0.98]) and ∆SBFBT (0.90 ± 0.05 [0.75-1.0]) to predict ∆VO2 ≥ 15% were higher than for other variables. CONCLUSION: A lower baseline SBFTCT and a greater ∆SBFBT can identify patients in whom VO2 will increase after fluid challenge, suggesting an improvement in cellular metabolism.

Alterations in Skin Blood Flow at the Fingertip Are Related to Mortality in Patients With Circulatory Shock.

OBJECTIVES: Skin blood flow is rapidly altered during circulatory shock and may remain altered despite apparent systemic hemodynamic stabilization. We evaluated whether changes in skin blood flow during circulatory shock were related to survival. DESIGN: Prospective study. SETTING: Thirty-five-bed medical-surgical university hospital department of intensive care. SUBJECTS: Twenty healthy volunteers and 70 patients with circulatory shock (< 12 hr duration), defined as the need for vasopressors to maintain mean arterial pressure greater than or equal to 65 mm Hg and signs of altered tissue perfusion. INTERVENTIONS: We assessed skin blood flow using skin laser Doppler on the fingertip for 3 minutes at basal temperature (SBFBT) and at 37°C (SBF37) (thermal challenge test) once in volunteers and at the time of inclusion and after 6, 24, 48, 72, and 96 hours in patients with shock. Capillary refill time and peripheral perfusion index were measured at the same time points on the contralateral hand. MEASUREMENTS AND MAIN RESULTS: The thermal challenge response (ΔSBF/ΔT) was calculated using the following formula: (SBF37-SBFBT)/(37-basal temperature). Area under the receiver operating characteristic curves were calculated to evaluate variables predictive of ICU mortality. At inclusion, skin blood flow and ΔSBF/ΔT were lower in patients than in volunteers. Baseline skin blood flow (31 [17-113] vs 16 [9-32] arbitrary perfusion units; p = 0.01) and ΔSBF/ΔT (4.3 [1.7-10.9] vs 0.9 [0.4-2.9] arbitrary perfusion unit/s) were greater in survivors than in nonsurvivors. Capillary refill time was shorter in survivors than in nonsurvivors; peripheral perfusion index was similar in the two groups. ΔSBF/ΔT (area under the receiver operating characteristic curve 0.94 [0.88-0.99]) and SBFBT (area under the receiver operating characteristic curve 0.83 [0.73-0.93]) had the best predictive value for ICU mortality with cutoff values less than or equal to 1.25 arbitrary perfusion unit/°C (sensitivity 88%, specificity 89%) and less than or equal to 21 arbitrary perfusion unit (sensitivity 84%, specificity 81%), respectively. CONCLUSIONS: Alterations in fingertip skin blood flow can be evaluated using a laser Doppler thermal challenge technique in patients with circulatory shock and are directly related to outcome. These novel monitoring techniques could potentially be used to guide resuscitation.

Systematic Review and Meta-Analysis of Effects of Transfusion on Hemodynamic and Oxygenation Variables.

OBJECTIVES: RBC transfusions can increase oxygen availability to the tissues, but studies have provided conflicting results. The objectives of this study were, therefore, to evaluate, using systematic review and meta-analysis, the effects of transfusion on hemodynamic/oxygenation variables in patients without acute bleeding. DATA SOURCES: PubMed, Scopus, Cochrane Database of Systematic Reviews, and Embase from inception until June 30, 2019. STUDY SELECTION: All articles that reported values of prespecified hemodynamic or oxygenation variables before and after RBC transfusion. DATA EXTRACTION: Publication year, number of patients, number of transfusions and the type of population studied, hemodynamic and oxygenation data (heart rate, cardiac index, mixed venous oxygen saturation or central venous oxygen saturation, oxygen delivery index, oxygen consumption index, oxygen extraction ratio, arteriovenous oxygen difference and arterial blood lactate) before and after transfusion. We performed a meta-analysis for each variable for which there were sufficient data to estimate mean differences. We also performed subgroup analyses comparing septic with nonseptic patients. DATA SYNTHESIS: We retrieved 6,420 studies; 33 met the inclusion criteria, 14 of which were in patients with sepsis. In the meta-analysis, the estimated mean differences and 95% CIs comparing the periods before and after transfusion were -0.0 L/min/m (-0.1 to 0.1 L/min/m) (p = 0.86) for cardiac index; -1.8 beats/min (-3.7 to 0.1 beats/min) (p = 0.06) for heart rate; 96.8 mL/min/m (71.1-122.5 mL/min/m) (p < 0.01) for oxygen delivery index; 2.9% (2.2-3.5%) (p < 0.01) for mixed venous oxygen saturation or central venous oxygen saturation; -3.7% (-4.4% to -3.0%) (p < 0.01) for oxygen extraction ratio; and 4.9 mL/min/m (0.9-9.0 mL/min/m) (p = 0.02) for oxygen consumption index. The estimated mean difference for oxygen consumption index in the patients with sepsis was 8.4 mL/min/m (2.3-14.5 mL/min/m; p = 0.01). CONCLUSIONS: Transfusion was not associated with a decrease in mean cardiac output or mean heart rate. The increase in mean oxygen delivery following transfusion was associated with an increase in mean oxygen consumption after transfusion, especially in patients with sepsis.

Hypertonic Saline in Human Sepsis: A Systematic Review of Randomized Controlled Trials.

The role of hypertonic saline in sepsis remains unclear because clinical data are limited and the balance between beneficial and adverse effects is not well defined. In this systematic literature review, we searched PubMed and Embase to identify all randomized controlled trials up until January 31, 2018 in which hypertonic saline solutions of any concentration were used in patients of all ages with sepsis and compared to a cohort of patients receiving an isotonic fluid. We identified 8 randomized controlled trials with 381 patients who had received hypertonic saline. Lower volumes of hypertonic saline than of isotonic solutions were needed to achieve the desired hemodynamic goals (standardized mean difference, -0.702; 95% CI, -1.066 to -0.337; P < .001; moderate-quality evidence). Hypertonic saline administration was associated with a transient increase in sodium and chloride concentrations without adverse effects on renal function (moderate-quality evidence). Some data suggested a beneficial effect of hypertonic saline solutions on some hemodynamic parameters and the immunomodulatory profile (very low-quality evidence). Mortality rates were not significantly different with hypertonic saline than with other fluids (odds ratio, 0.946; 95% CI, 0.688-1.301; P = .733; low-quality evidence). In conclusion, in our meta-analysis of studies in patients with sepsis, hypertonic saline reduced the volume of fluid needed to achieve the same hemodynamic targets but did not affect survival.

Skin microcirculatory reactivity assessed using a thermal challenge is decreased in patients with circulatory shock and associated with outcome.

BACKGROUND: Shock states are characterized by impaired tissue perfusion and microcirculatory alterations, which are directly related to outcome. Skin perfusion can be noninvasively evaluated using skin laser Doppler (SLD), which, when coupled with a local thermal challenge, may provide a measure of microcirculatory reactivity. We hypothesized that this microvascular reactivity would be impaired in patients with circulatory shock and would be a marker of severity. METHODS: We first evaluated skin blood flow (SBF) using SLD on the forearm and on the palm in 18 healthy volunteers to select the site with maximal response. Measurements were taken at 37 °C (baseline) and repeated at 43 °C. The 43 °C/37 °C SBF ratio was calculated as a measure of microvascular reactivity. We then evaluated the SBF in 29 patients with circulatory shock admitted to a 35-bed department of intensive care and in a confirmatory cohort of 35 patients with circulatory shock. RESULTS: In the volunteers, baseline SBF was higher in the hand than in the forearm, but the SBF ratio was lower (11.2 [9.4-13.4] vs. 2.0 [1.7-2.6], p < 0.01) so we used the forearm for our patients. Baseline forearm SBF was similar in patients with shock and healthy volunteers, but the SBF ratio was markedly lower in the patients (2.6 [2.0-3.6] vs. 11.2 [9.4-13.4], p < 0.01). Shock survivors had a higher SBF ratio than non-survivors (3.2 [2.2-6.2] vs. 2.3 [1.7-2.8], p < 0.01). These results were confirmed in the second cohort of 35 patients. In multivariable analysis, the APACHE II score and the SBF ratio were independently associated with mortality. CONCLUSIONS: Microcirculatory reactivity is decreased in patients with circulatory shock and has prognostic value. This simple, noninvasive test could help in monitoring the peripheral microcirculation in acutely ill patients.

Peripheral Muscle Near-Infrared Spectroscopy Variables are Altered Early in Septic Shock.

BACKGROUND: Noninvasive evaluation of muscle perfusion using near-infrared spectroscopy (NIRS) coupled with a vascular occlusion test (VOT) may provide an early and simple marker of altered perfusion and microcirculatory function in sepsis. OBJECTIVE: The aim of the study was to compare the time-course of NIRS-derived variables with systemic measures of perfusion in an experimental model of peritonitis. METHODS: Peritonitis was induced in eight anesthetized, mechanically ventilated, adult sheep (24-34 kg), by injecting autologous feces into the peritoneal cavity. Animals were followed until death or for a maximum of 30 h. Muscle tissue oxygen saturation (StO2) was determined using NIRS on the right posterior leg and arterial VOTs were performed by intermittent intra-aortic balloon inflation. Microdialysis was used to measure muscle lactate and pyruvate levels. RESULTS: Muscle StO2 was significantly lower than baseline values from 8 h after sepsis induction, but with considerable intersubject variability. The NIRS VOT ascending (Asc) slope decreased to values <120%/min in most animals from 12 h after sepsis induction. Muscle lactate/pyruvate ratios were higher than baseline from 16 h after sepsis induction. Mixed venous oxygen saturation (SvO2) decreased to <70% and blood lactate levels increased to >2 mmol/L in most of the animals only 24 and 28 h after sepsis induction, respectively. Muscle NIRS StO2 correlated strongly with femoral venous oxygen saturation (r = 0.820) and moderately with SvO2 (r = 0.436). CONCLUSIONS: The muscle NIRS Asc slope after a VOT is altered earlier than global markers of tissue hypoperfusion during sepsis. This simple noninvasive test can detect early changes in peripheral perfusion in sepsis.

Endocan as an early biomarker of severity in patients with acute respiratory distress syndrome.

BACKGROUND: Plasma concentrations of endocan, a proteoglycan preferentially expressed in the pulmonary vasculature, may represent a biomarker of lung (dys)function. We sought to determine whether the measurement of plasma endocan levels early in the course of acute respiratory distress syndrome (ARDS) could help predict risk of death or of prolonged ventilation. METHODS: All patients present in the department of intensive care during a 150-day period were screened for ARDS (using the Berlin definition). Endocan concentrations were measured at the moment of ARDS diagnosis (T0) and the following morning (T1). We compared data from survivors and non-survivors and data from survivors with less than 10 days of ventilator support (good evolution) and those who died or needed more than 10 days of mechanical ventilation (poor evolution). Results are presented as numbers (percentages), mean ± standard deviation or medians (percentile 25-75). RESULTS: Ninety-six consecutive patients were included [median APACHE II score of 21 (17-27) and SOFA score of 9 (6-12), PaO2/FiO2 ratio 155 (113-206)]; 64 (67%) had sepsis and 51 (53%) were receiving norepinephrine. Non-survivors were older (66 ± 15 vs. 59 ± 18 years, p = 0.045) and had higher APACHE II scores [27 (22-30) vs. 20 (15-24), p < 0.001] and blood lactate concentrations at study inclusion [2.1 (1.3-4.0) vs. 1.5 (0.9-2.6) mmol/L, p = 0.024] than survivors, but PaO2/FiO2 ratios [150 (116-207) vs. 158 (110-206), p = 0.95] were similar in the two groups. Endocan concentrations on the day after ARDS diagnosis were significantly higher in patients with poor evolution than in those with good evolution [12.0 (6.8-18.6) vs. 7.2 (5.4-12.5), p < 0.01]. CONCLUSION: Blood endocan concentrations early in the evolution of ARDS may be a useful marker of disease severity.

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.

Administration of Tetrahydrobiopterin (BH4) Protects the Renal Microcirculation From Ischemia and Reperfusion Injury.

BACKGROUND: Abdominal aortic aneurysm surgery with suprarenal cross-clamping is often associated with renal injury. Although the mechanism underlying such injury is unclear, tissue ischemia and reperfusion, which induces endothelial dysfunction and decreases the availability of tetrahydrobiopterin (BH4), may play a role. We evaluated whether BH4 administration prevents renal ischemia/reperfusion injury in an animal model of aortic cross-clamping. METHODS: Nineteen anesthetized, mechanically ventilated, and invasively monitored adult sheep were randomized into 3 groups: sham animals (n = 5) that underwent surgical preparation but no aortic clamping; an ischemia/reperfusion group (n = 7), where the aorta was clamped above the renal arteries for 1 hour, and a BH4 group (n = 7), in which animals received 20 mg/kg of BH4 followed by aortic cross-clamp for 1 hour. Animals were followed for a maximum of 6 hours after reperfusion. The renal microcirculation was evaluated at baseline (before clamping), and 1, 4, and 6 hours after reperfusion using side-stream dark field videomicroscopy. The renal lactate-to-pyruvate ratio was evaluated using microdialysis. The primary outcome was the change in proportion of small perfused vessels before and after injury. Secondary outcomes were renal tissue redox state and renal function. RESULTS: Ischemia/reperfusion injury was associated with increases in heart rate and mean arterial pressure, which were blunted by BH4 administration. From the first to the sixth hour after reperfusion, the small vessel density (estimated mean difference [EMD], 1.03; 95% confidence interval [CI], 0.41-1.64; P = .003), perfused small vessel density (EMD, 0.84; 95% CI, 0.29-1.39; P = .005), and proportion of perfused small vessels (EMD, 8.60; 95% CI, 0.85-16.30; P = .031) were altered less in the BH4 than in the ischemia/reperfusion group. The renal lactate-to-pyruvate ratios were lower in the cortex in the BH4 than in the ischemia/reperfusion group from the first to the sixth hour after reperfusion (EMD, -19.16; 95% CI, -11.06 to 33.16; P = .002) and in the medulla from the first to the fourth hour (EMD, -26.62; 95% CI, -18.32 to 38.30; P = .020; and EMD, -8.68; 95% CI, -5.96 to 12.65; P = .019). At the sixth hour, serum creatinine was lower in the BH4 than in the ischemia/reperfusion group (EMD, -3.36; 95% CI, -0.29 to 1.39; P = .026). CONCLUSIONS: In this sheep model of renal ischemia/reperfusion, BH4 pretreatment reduced renal microvascular injury and improved renal metabolism and function. Further work is needed to clarify the potential role of BH4 in ischemia/reperfusion injury.

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.

The Harmful Effects of Hypertonic Sodium Lactate Administration in Hyperdynamic Septic Shock.

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 Ringer's 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.

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.