Microvascular reactivity is altered early in patients with acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with vascular endothelial dysfunction. The resultant microvascular reactivity can be assessed non-invasively using near-infrared spectroscopy (NIRS) and a vascular occlusion test (VOT) and changes have been correlated with severity of organ dysfunction and mortality in other critically ill populations. We used NIRS to study the presence of microcirculatory alterations in patients with ARDS. METHODS: We studied 27 healthy volunteers and 32 ARDS patients admitted to our intensive care department. NIRS measurements were performed within 24 h after diagnosis (Berlin definition). VOTs were performed by inflating an arm-cuff to a pressure greater than the systolic pressure for 3 min, followed by rapid deflation. The descending (Desc) and ascending (Asc) thenar muscle oxygen saturation (StO2) slopes were calculated. We compared data from volunteers with those from ARDS patients, from ARDS survivors and non-survivors, and from ARDS survivors who required <7 days ventilatory support (good evolution) with those who required >7 days support or died (poor evolution). RESULTS: ARDS patients had lower StO2 values [75(67-80) vs 79(76-81) %, p = 0.04] and Asc slopes [185(115-233) vs 258(216-306) %/min, p < 0.01] than healthy volunteers, but Desc slopes were similar. The Asc slope was lower in the patients with a poor evolution than in the other patients [121(90-209) vs 222(170-293) %/min, p < 0.01], and in the non-survivors than in the survivors [95(73-120) vs 212(165-252) %/min, p < 0.01]. CONCLUSIONS: In ARDS patients, microvascular reactivity is altered early, and the changes are directly related to the severity of the disease. The ascending slope is the best determinant of outcome.

Current haemodynamic management of septic shock.

Early and adequate resuscitation of patients with acute circulatory failure is important to restore the balance between oxygen needs and delivery. Haemodynamic management can globally be separated into three categories according to the VIP mnemonic - Ventilate, Infuse, Pump - which should be considered simultaneously in the patient with shock. Sufficient oxygen should be given early, and endotracheal intubation and mechanical ventilation performed without hesitation if there is any indication that oxygenation is inadequate. Fluids should be administered using the SOSD mnemonic - Salvage, Optimization, Stabilization, De-escalation. After initial liberal administration, ongoing requirements should be guided by repeated fluid challenges using a combination of balanced crystalloid solutions and colloid. Noradrenaline is the vasopressor of choice and should be started early. Dobutamine may be needed to improve myocardial contractility and cardiac output. Haemodynamic support should be personalized according to individual patient characteristics and global and regional parameters of haemodynamic and oxygenation status.

ISCHEMIC CONDITIONING PROTECTS THE MICROCIRCULATION, PRESERVES ORGAN FUNCTION, AND PROLONGS SURVIVAL IN SEPSIS.

Ischemic conditioning induces a series of cellular modifications that may prevent injury from further hypoxic episodes, but there are few data in sepsis. In this randomized controlled study, we evaluated the effects of ischemic conditioning on the microcirculation, organ function, and survival time in an ovine model of septic shock.Sepsis was induced in 14 anesthetized, mechanically ventilated adult sheep by injecting autologous feces into the abdominal cavity. Animals were then randomized to ischemic pre- and post-conditioning or no conditioning (both n = 7). Remote ischemic conditioning was performed by inflating the balloon of a catheter in the aortic bifurcation for 2 min, followed by a 4-min deflation period. The procedure was performed four times before sepsis induction and 4-hourly afterward. Animals were followed until death or for a maximum of 30 h. Hemodynamic, oxygenation, and microcirculatory variables were monitored. The conditioned group had higher mixed venous oxygen saturation from 8 h after randomization, higher cardiac index, and oxygen delivery from 16 h, and higher mean arterial pressure and lower lactate levels from 20 h. They also had greater renal blood flow, urine output, and creatinine clearance. Microcirculatory variables were better preserved in the conditioned than in the control group from 6 h after randomization: the median proportion of perfused vessels was 91 (89-93)% versus 89 (86-90)% (P = 0.024) and there was less heterogeneity. Oliguria, hypotension, and death occurred later in the conditioned than in the control group. In this sepsis model, remote ischemic pre- and post-conditioning therefore decreased organ dysfunction, preserved the microcirculation, and prolonged survival.

Treatment of intraparenchymal hypertension with hyperosmotic therapy: hypertonic saline 7.45% vs. mannitol 20.

BACKGROUND: There is controversy about the superiority of hypertonic saline (HS) over mannitol (M) to treat intracranial hypertension (ICHT). We aim to compare the effects of HS 7.45% vs. M 20% on systemic hemodynamics, intracranial pressure (ICP) and brain regional metabolism or oxygenation during experimental ICHT. METHODS: In 16 sedated and mechanically-ventilated pigs, ICHT was obtained by inflation of a balloon catheter inserted in the right frontal lobe. Ventilation was set to maintain normoxia and normocapnia. Mean arterial pressure was maintained above 80 mmHg by IV isotonic fluids. Animals were randomized to receive a 30-minute IV load of 255 mOsm/dose of either HS 7.45% (N.=7) or M 20% (N.=7). Brain oxygen tension (PbO2) was measured hourly by a parenchymal Clark electrode and cerebral lactate/pyruvate ratio (LPR) was assessed using brain microdialysis. A linear mixed model was used to analyze the time course of considered variables from baseline to 180 minutes after infusion. RESULTS: There was no significant difference in systemic hemodynamics between the two groups over the study period. HS 7.45% administration maintained a lower ICP and a higher cerebral perfusion pressure at 180 minutes, but with no significant difference in PbO2 or LPR. CONCLUSIONS: In this model of ICHT, only small differences were found in maintaining a better cerebral perfusion using HS 7.45% compared to M 20% in the early phase of therapy. These differences were not dependent on changes in systemic hemodynamics and did not result in significant differences in brain regional oxygenation or metabolism.

Near infrared spectroscopy (NIRS) to assess the effects of local ischemic preconditioning in the muscle of healthy volunteers and critically ill patients.

Near-infrared spectroscopy (NIRS) permits non-invasive evaluation of tissue oxygen saturation (StO2). A vascular occlusion test (VOT) produces transient controlled ischemia similar to that used in ischemic preconditioning. We hypothesized that we could evaluate local responses to ischemic preconditioning by performing repeated VOTs and observing the changes in different NIRS VOT-derived variables. In healthy volunteers (n=20), four VOTs were performed at 30-min intervals on one day and, in a second group (n=21), two VOTs with time intervals of 5, 15 or 30min were performed on 3 separate days. Two cohorts of patients, one with circulatory shock (n=23) and a hemodynamically stable group (n=20), were also studied, repeating the VOT twice with a 5-min interval. In the 1-day volunteers, there was a median decrease of 15 (6-21)% in the Desc slope (StO2 decrease during VOT) after the second VOT, but no significant change in the Asc slope (StO2 increase after VOT). In the 3-day volunteers, the Desc slope also decreased, regardless of the time interval between VOTs. There was no overall decrease in the Desc slope in either patient cohort with repeated VOTs but there was marked individual patient variability. Patients in whom the Desc slope decreased had less organ dysfunction at admission, required less norepinephrine (0.00 vs 0.08mcg/kg/min, p=0.02), less frequently had sepsis (12 vs 50%, p=0.02) and had a lower mortality (6 vs 39%, p=0.03) compared to those in whom it did not decrease. Repeated NIRS VOT can non-invasively assess the local effects of ischemic preconditioning in the muscle.

Crystalloids versus colloids: exploring differences in fluid requirements by systematic review and meta-regression.

BACKGROUND: Positive fluid balance has been associated with worse outcomes, and knowledge of differences in the amounts of different types of fluid needed to achieve the same end points may have important clinical implications. Large molecules persist longer in the blood vessels than smaller molecules, such that less IV colloid may be needed to achieve similar hemodynamic end points compared with crystalloid. Recent clinical data have, however, challenged this physiological concept, with investigators reporting lower-than-expected crystalloid/colloid ratios in various populations. METHODS: We performed a systematic search in MEDLINE, EMBASE, and CENTRAL up to December 18, 2013, to retrieve all studies comparing (any) crystalloid with (any) colloid in all types of patients. The crystalloid/colloid ratio was calculated for each study. Descriptive analysis was performed for all studies, and a meta-analysis was performed in those studies reporting full data (in terms of means and standard deviations) of infused fluid volumes. Studies were grouped according to study and population characteristics. A meta-regression analysis was then performed to evaluate some of the possible reasons for differences in crystalloid/colloid ratios across studies. RESULTS: From 976 studies, 48 were retained for the final analysis; 24 of the studies had sufficient data for meta-analysis. The crystalloid/colloid ratio across all the studies included in the meta-analysis was 1.5 (95% confidence interval, 1.36-1.65) with marked heterogeneity among studies (I = 94%). From the meta-regression analysis, decade of publication across all publications (P = 0.001) and concentration (tonicity) in the subgroup of albumin studies (P = 0.001) were associated with the administered crystalloid/colloid ratio. The reduction in heterogeneity among studies for all publications in the meta-regression was minimal, with the maximal decrease obtained when decade of publication was considered (R = 12%). CONCLUSIONS: Greater fluid volumes are required to meet the same targets with crystalloids than with colloids, with an estimated ratio of 1.5 (1.36-1.65), but there is marked heterogeneity among studies. The crystalloid/colloid ratio seems to have decreased over the years, and differences in ratios are correlated with the concentration of albumin solutions; however, the main reasons behind the high heterogeneity among studies remain unclear.

Normobaric hyperoxia alters the microcirculation in healthy volunteers.

The use of high concentrations of inhaled oxygen has been associated with adverse effects but recent data suggest a potential therapeutic role of normobaric hyperoxia (NH) in sepsis and cerebral ischemia. Hyperoxia may induce vasoconstriction and alter endothelial function, so we evaluated its effects on the microcirculation in 40 healthy adult volunteers using side-stream dark field (SDF) video-microscopy on the sublingual area and near-infrared spectroscopy (NIRS) on the thenar eminence. In a first group of volunteers (n=18), measurements were taken every 30 min: at baseline in air, during NH (close to 100% oxygen via a non-rebreathing mask) and during recovery in air. In a second group (n=22), NIRS measurements were taken in NH or ambient air on two separate days to prevent any potential influence of repeated NIRS measurements. NH significantly decreased the proportion of perfused vessels (PPV) from 92% to 66%, perfused vessel density (PVD) from 11.0 to 7.3 vessels/mm, perfused small vessel density (PSVD) from 9.0 to 5.8 vessels/mm and microvascular flow index (MFI) from 2.8 to 2.0, and increased PPV heterogeneity from 7.5% to 30.4%. Thirty minutes after return to air, PPV, PVD, PSVD and MFI remained partially altered. During NH, NIRS descending slope and NIRS muscle oxygen consumption (VO2) decreased from 8.5 to 7.9%/s and 127 to 103 units, respectively, in the first group and from 10.7 to 9.4%/s and 150 to 115 units in the second group. NH, therefore, alters the microcirculation in healthy subjects, decreasing capillary perfusion and VO2 and increasing the heterogeneity of the perfusion.

C-reactive protein levels after cardiac arrest in patients treated with therapeutic hypothermia.

AIM: Prognostication of outcome after cardiac arrest (CA) is challenging. We assessed the prognostic value of daily blood levels of C-reactive protein (CRP), a cheap and widely available inflammatory biomarker, after CA. METHODS: We reviewed the data of all patients admitted to our intensive care unit (ICU) after CA between January 2009 and December 2011 and who survived for at least 24h. We collected demographic data, CA characteristics (initial rhythm; location of arrest; time to return of spontaneous circulation [ROSC]), occurrence of infection, ICU survival and neurological outcome at three months (good=cerebral performance category [CPC] 1-2; poor=CPC 3-5). CRP levels were measured daily from admission to day 3. RESULTS: A total of 130 patients were admitted after successful resuscitation from CA and survived more than 24h; 76 patients (58%) developed an infection and overall mortality was 56%. CRP levels increased from admission to day 3. CRP levels were higher in in-hospital than in out-of-hospital CA, especially on admission and day 1 (44.1 vs. 2.1 mgL(-1) and 74.5 vs. 29.5 mgL(-1), respectively; p<0.001), and in patients with non-shockable than in those with shockable rhythms. In a logistic regression model, high CRP levels on admission were independently associated with poor neurological outcome at 3 months. CONCLUSION: CRP levels increase in the days following successful resuscitation of CA. Higher CRP levels in patients with in-hospital CA, non-shockable rhythms and infection, suggest a greater inflammatory response in these patients. High CRP levels on admission may identify patients at high-risk of poor outcome and could be a target for future therapies.

Pathophysiology of microcirculatory dysfunction and the pathogenesis of septic shock.

Multiple experimental and human trials have shown that microcirculatory alterations are frequent in sepsis. In this review, we discuss the various mechanisms that are potentially involved in their development and the implications of these alterations. Endothelial dysfunction, impaired inter-cell communication, altered glycocalyx, adhesion and rolling of white blood cells and platelets, and altered red blood cell deformability are the main mechanisms involved in the development of these alterations. Microcirculatory alterations increase the diffusion distance for oxygen and, due to the heterogeneity of microcirculatory perfusion in sepsis, may promote development of areas of tissue hypoxia in close vicinity to well-oxygenated zones. The severity of microvascular alterations is associated with organ dysfunction and mortality. At this stage, therapies to specifically target the microcirculation are still being investigated.