Glenn Hernandez

Gut mucosal atrophy after a short enteral fasting period in critically ill patients.

PURPOSE The purpose of this study was to evaluate the presence of gut mucosal atrophy and changes in mucosal permeability in critically ill patients after a short fasting period. MATERIALS AND METHODS Fifteen critically ill patients underwent a period of enteral fasting of at least 4 days (mean 7.8 days). We took the following measurements the day before initiating enteral nutrition: indirect calorimetry, serum albumin, prealbumin, and lymphocyte count. We also performed a duodenal endoscopic biopsy with histopathological and mucosal morphometric analysis including villus height and crypt depth. The lactulose-mannitol test was performed to assess gut permeability. A total of 28 healthy volunteers served as controls for duodenal biopsy or lactulose-mannitol test. Clinical data, such as length of fasting, severity score, and previous parenteral nutritional support, were recorded. RESULTS We found gut mucosal atrophy, expressed as a decrease in villus height and crypt depth, in patients compared with controls. The patients also exhibited an abnormal lactulose-mannitol test. Morphometric changes did not correlate with permeability. Further, we found no correlation between the results of the lactulose-mannitol test and of mucosal morphometry with clinical data. CONCLUSIONS We found that a short period of enteral fasting was associated with significant duodenal mucosal atrophy and abnormal gut permeability in critically ill patients.

Intra-abdominal hypertension: Incidence and association with organ dysfunction during early septic shock

PURPOSE The objective of this article is to study the cumulative incidence of intra-abdominal hypertension (IAH) in septic shock (SS) patients during the first 72 hours of intensive care unit (ICU) admission and to determine if the presence and severity of IAH are associated with sepsis morbidity and mortality. MATERIALS AND METHODS Eighty-one consecutive SS patients admitted to a surgical-medical ICU of an academic university hospital (January 2005 to January 2006) were included. Intra-abdominal pressure (IAP) and abdominal perfusion pressure (APP) were measured every 6 h (intermittently) for 72 h. Intra-abdominal pressure was registered as minimal, mean, and maximal values per day, during shock and throughout the study period. Intra-abdominal hypertension was diagnosed if IAP remained 12 mm Hg or higher on 2 consecutive measurements and stratified according to the most recent consensus definition (www.wsacs.org). RESULTS According to maximal and mean IAP values, 67 (82.7%) and 62 (76.5%) of the patients developed IAH during the study period, respectively. Mean IAP values remained stable throughout the study period. Surgical patients had a higher incidence of IAH than medical patients (93% vs 73%, P < .009). Maximal IAPs were normally distributed, with nonsurvivors exhibiting significantly higher IAP levels during shock (survivors, 17.2 +/- 5.3; nonsurvivors, 19.9 +/- 5.6 mm Hg; P < .04). Patients with IAH exhibited significantly lower values of APP and diuresis, higher values of lactate and creatinine, and higher maximal norepinephrine doses, and were more frequently mechanically ventilated (P < .05 for all). Increasing degrees of IAH and the development of the abdominal compartment syndrome were associated with lower APP and higher maximal serum creatinine levels (P < .03 for both). CONCLUSIONS Septic shock patients have a very high incidence of IAH, which seems to be associated with the severity of shock and could be related to the development of organ dysfunctions, particularly renal dysfunction. Intra-abdominal pressure should be routinely monitored during the course of SS.

The endothelium in sepsis

ABSTRACT Sepsis affects practically all aspects of endothelial cell (EC) function and is thought to be the key factor in the progression from sepsis to organ failure. Endothelial functions affected by sepsis include vasoregulation, barrier function, inflammation, and hemostasis. These are among other mechanisms often mediated by glycocalyx shedding, such as abnormal nitric oxide metabolism, up-regulation of reactive oxygen species generation due to down-regulation of endothelial-associated antioxidant defenses, transcellular communication, proteases, exposure of adhesion molecules, and activation of tissue factor. This review covers current insight in EC-associated hemostatic responses to sepsis and the EC response to inflammation. The endothelial cell lining is highly heterogeneous between different organ systems and consequently also in its response to sepsis. In this context, we discuss the response of the endothelial cell lining to sepsis in the kidney, liver, and lung. Finally, we discuss evidence as to whether the EC response to sepsis is adaptive or maladaptive. This study is a result of an Acute Dialysis Quality Initiative XIV Sepsis Workgroup meeting held in Bogota, Columbia, between October 12 and 15, 2014.

Persistent sepsis-induced hypotension without hyperlactatemia: Is it really septic shock?

PURPOSE The prognostic value of hyperlactatemia in septic shock is unquestionable. However, as current definitions do not include hyperlactatemia as a mandatory criterion, some hypotensive patients may be diagnosed as having septic shock despite exhibiting normolactatemia. The significance of persistent sepsis-induced hypotension without hyperlactatemia is unclear. Is it really septic shock? Our aim was to determine differences in outcome between patients diagnosed as having septic shock but exhibiting normal vs elevated lactate levels during evolution. We also explored the potential implications of including hyperlactatemia as an obligatory diagnostic criterion. METHODS We performed retrospective analyses on a cohort of 302 septic shock patients. RESULTS When we divided patients according to the presence of hyperlactatemia, 34% evolved without hyperlactatemia and exhibited a very low mortality risk (7.7% compared with 42.9% of those with hyperlactatemia). These patients also presented less severe organ dysfunctions and higher central venous O(2) saturation values, and required lower norepinephrine doses. The potential inclusion of hyperlactatemia in septic shock definition would reduce incidence in 34% but increase absolute mortality risk in 11%. CONCLUSIONS Persistent sepsis-induced hypotension without hyperlactatemia may not constitute a real septic shock. Our results support the need to review the current definition of septic shock. Hyperlactatemia could represent an objective parameter worth to be explored as a potential diagnostic criterion for septic shock.

Impact of emergency intubation on central venous oxygen saturation in critically ill patients: a multicenter observational study

IntroductionCentral venous oxygen saturation (ScvO2) has emerged as an important resuscitation goal for critically ill patients. Nevertheless, growing concerns about its limitations as a perfusion parameter have been expressed recently, including the uncommon finding of low ScvO2 values in patients in the intensive care unit (ICU). Emergency intubation may induce strong and eventually divergent effects on the physiologic determinants of oxygen transport (DO2) and oxygen consumption (VO2) and, thus, on ScvO2. Therefore, we conducted a study to determine the impact of emergency intubation on ScvO2.MethodsIn this prospective multicenter observational study, we included 103 septic and non-septic patients with a central venous catheter in place and in whom emergency intubation was required. A common intubation protocol was used and we evaluated several parameters including ScvO2 before and 15 minutes after emergency intubation. Statistical analysis included chi-square test and t test.ResultsScvO2 increased from 61.8 ± 12.6% to 68.9 ± 12.2%, with no difference between septic and non-septic patients. ScvO2 increased in 84 patients (81.6%) without correlation to changes in arterial oxygen saturation (SaO2). Seventy eight (75.7%) patients were intubated with ScvO2 less than 70% and 21 (26.9%) normalized the parameter after the intervention. Only patients with pre-intubation ScvO2 more than 70% failed to increase the parameter after intubation.ConclusionsScvO2 increases significantly in response to emergency intubation in the majority of septic and non-septic patients. When interpreting ScvO2 during early resuscitation, it is crucial to consider whether the patient has been recently intubated or is spontaneously breathing.

Microcirculation in sepsis: new perspectives.

Microcirculatory dysfunction has been recently recognized as a key pathophysiologic process in the evolution of sepsis. In the present review, we discuss fundamental aspects of microcirculatory abnormalities during septic shock, including pathogenic mechanisms, technological assessment, clinical correlates and potential therapies. The most important function of the microcirculation is the regulation and distribution of flow within the different organs. In septic shock, microcirculatory dysfunction may arise as a result of several factors such as endothelial dysfunction, leukocyte-endothelium interactions, coagulation and inflammatory disorders, hemorheologic abnormalities, and functional shunting. Severity and persistence of these microcirculatory abnormalities are associated with bad prognosis and are not necessarily predicted by systemic variables. The introduction of bedside techniques that allow evaluation of the microcirculation into clinical practice has opened up a new field of functional hemodynamic monitoring. Recent data suggest that microcirculatory abnormalities can be staged in severity. Some microcirculatory indices are more accurately related to morbidity and mortality, and thus a definition of clinically relevant microcirculatory abnormalities is feasible. On the other hand, although several systemic variables do not predict microcirculatory status, high norepinephrine (NE) requirements and hyperlactatemia are associated with a much higher prevalence of relevant microcirculatory derangements. Therefore, severe septic shock patients could represent a more precise target for interventions, particularly in microcirculation-oriented clinical trials. Clinical research has identified various therapeutic approaches that are successful in modifying the microcirculation. Future research must determine whether some of these approaches are successful in improving outcome of critically ill patients by recruiting the microcirculation.

When to stop septic shock resuscitation: clues from a dynamic perfusion monitoring

BackgroundThe decision of when to stop septic shock resuscitation is a critical but yet a relatively unexplored aspect of care. This is especially relevant since the risks of over-resuscitation with fluid overload or inotropes have been highlighted in recent years. A recent guideline has proposed normalization of central venous oxygen saturation and/or lactate as therapeutic end-points, assuming that these variables are equivalent or interchangeable. However, since the physiological determinants of both are totally different, it is legitimate to challenge the rationale of this proposal. We designed this study to gain more insights into the most appropriate resuscitation goal from a dynamic point of view. Our objective was to compare the normalization rates of these and other potential perfusion-related targets in a cohort of septic shock survivors.MethodsWe designed a prospective, observational clinical study. One hundred and four septic shock patients with hyperlactatemia were included and followed until hospital discharge. The 84 hospital-survivors were kept for final analysis. A multimodal perfusion assessment was performed at baseline, 2, 6, and 24 h of ICU treatment.ResultsSome variables such as central venous oxygen saturation, central venous-arterial pCO2 gradient, and capillary refill time were already normal in more than 70% of survivors at 6 h. Lactate presented a much slower normalization rate decreasing significantly at 6 h compared to that of baseline (4.0 [3.0 to 4.9] vs. 2.7 [2.2 to 3.9] mmol/L; p < 0.01) but with only 52% of patients achieving normality at 24 h. Sublingual microcirculatory variables exhibited the slowest recovery rate with persistent derangements still present in almost 80% of patients at 24 h.ConclusionsPerfusion-related variables exhibit very different normalization rates in septic shock survivors, most of them exhibiting a biphasic response with an initial rapid improvement, followed by a much slower trend thereafter. This fact should be taken into account to determine the most appropriate criteria to stop resuscitation opportunely and avoid the risk of over-resuscitation.

Persistently high venous-to-arterial carbon dioxide differences during early resuscitation are associated with poor outcomes in septic shock.

IntroductionVenous-to-arterial carbon dioxide difference (Pv-aCO2) may reflect the adequacy of blood flow during shock states. We sought to test whether the development of Pv-aCO2 during the very early phases of resuscitation is related to multi-organ dysfunction and outcomes in a population of septic shock patients resuscitated targeting the usual oxygen-derived and hemodynamic parameters.MethodsWe conducted a prospective observational study in a 60-bed mixed ICU in a University affiliated Hospital. 85 patients with a new septic shock episode were included. A Pv-aCO2 value ≥ 6 mmHg was considered to be high. Patients were classified in four predefined groups according to the Pv-aCO2 evolution during the first 6 hours of resuscitation: (1) persistently high Pv-aCO2 (high at T0 and T6); (2) increasing Pv-aCO2 (normal at T0, high at T6); (3) decreasing Pv-aCO2 (high at T0, normal at T6); and (4) persistently normal Pv-aCO2 (normal at T0 and T6). Multiorgan dysfunction at day-3 was compared for predefined groups and a Kaplan Meier curve was constructed to show the survival probabilities at day-28 using a log-rank test to evaluate differences between groups. A Spearman-Rho was used to test the agreement between cardiac output and Pv-aCO2. Finally, we calculated the mortality risk ratios at day-28 among patients attaining normal oxygen parameters but with a concomitantly increased Pv-aCO2.ResultsPatients with persistently high and increasing Pv-aCO2 at T6 had significant higher SOFA scores at day-3 (p < 0.001) and higher mortality rates at day-28 (log rank test: 19.21, p < 0.001) compared with patients who evolved with normal Pv-aCO2 at T6. Interestingly, a poor agreement between cardiac output and Pv-aCO2 was observed (r2 = 0.025, p < 0.01) at different points of resuscitation. Patients who reached a central venous saturation (ScvO)2 ≥ 70% or mixed venous oxygen saturation (SvO2) ≥ 65% but with concomitantly high Pv-aCO2 at different developmental points (i.e., T0, T6 and T12) had a significant mortality risk ratio at day-28.ConclusionThe persistence of high Pv-aCO2 during the early resuscitation of septic shock was associated with more severe multi-organ dysfunction and worse outcomes at day-28. Although mechanisms conducting to increase Pv-aCO2 during septic shock are insufficiently understood, Pv-aCO2 could identify a high risk of death in apparently resuscitated patients.

Evolution of peripheral vs metabolic perfusion parameters during septic shock resuscitation. A clinical-physiologic study

PURPOSE Perfusion assessment during septic shock resuscitation is difficult and usually complex determinations. Capillary refill time (CRT) and central-to-toe temperature difference (Tc-toe) have been proposed as objective reproducible parameters to evaluate peripheral perfusion. The comparative evolution of peripheral vs metabolic perfusion parameters in septic shock resuscitation has not been studied. We conducted a prospective observational clinical-physiologic study to address this subject. METHODS Patients with sepsis-related circulatory dysfunction were resuscitated according to a standard local algorithm. Perfusion assessment included serial determinations of metabolic (central venous O(2) saturation [Scvo(2)] and central venous to arterial Pco(2) gradient [P(cv-a)co(2)]) and peripheral perfusion parameters (CRT and Tc-toe, among others). Successful resuscitation was defined as a normal plasma lactate at 24 hours. RESULTS Forty-one patients were included. The presence of normal values for both CRT and Tc-toe considered together at 6 hours was independently associated with a successful resuscitation (P = .02), as compared with the behavior of metabolic parameters. Capillary refill time was the first parameter to be significantly normalized. CONCLUSION Early recovery of peripheral perfusion anticipates a successful resuscitation compared with traditional metabolic parameters in septic shock patients. Our findings support the inclusion of serial peripheral perfusion assessment in multimodal monitoring strategies for septic shock resuscitation.

The holistic view on perfusion monitoring in septic shock

Purpose of reviewTo review recent evidence concerning the interactions between hemodynamic and perfusion parameters during septic shock resuscitation, and to propose some basic foundations for a more comprehensive perfusion assessment. Recent findingsSeveral recent studies have expanded our knowledge about the physiologic determinants and limitations of currently used perfusion parameters such as central venous oxygen saturation and lactate. Macrohemodynamic, metabolic, peripheral and microcirculatory parameters tend to change in parallel in response to fluid loading during initial resuscitation. In contrast, perfusion markers are poorly correlated in patients who evolve with a persistent circulatory dysfunction. Therefore, assessment of perfusion status based solely on a single parameter can lead to inaccurate or misleading conclusions. SummaryAll individual perfusion parameters have extensive limitations to adequately reflect tissue perfusion during persistent sepsis-related circulatory dysfunction. A multimodal approach integrating macrohemodynamic, metabolic, peripheral and eventually microcirculatory perfusion parameters may overcome those limitations. This approach may also provide a thorough understanding on the predominant driving forces of hypoperfusion, and lead to physiologically oriented interventions.