Inadequate Tissue Oxygenation Research Articles

Stress-associated erythropoiesis initiation is regulated by type 1 conventional dendritic cells.

Erythropoiesis is an important response to certain types of stress, including hypoxia, hemorrhage, bone marrow suppression, and anemia, that result in inadequate tissue oxygenation. This stress-induced erythropoiesis is distinct from basal red blood cell generation; however, neither the cellular nor the molecular factors that regulate this process are fully understood. Here, we report that type 1 conventional dendritic cells (cDC1s), which are defined by expression of CD8α in the mouse and XCR1 and CLEC9 in humans, are critical for induction of erythropoiesis in response to stress. Specifically, using murine models, we determined that engagement of a stress sensor, CD24, on cDC1s upregulates expression of the Kit ligand stem cell factor on these cells. The increased expression of stem cell factor resulted in Kit-mediated proliferative expansion of early erythroid progenitors and, ultimately, transient reticulocytosis in the circulation. Moreover, this stress response was triggered in part by alarmin recognition and was blunted in CD24 sensor- and CD8α+ DC-deficient animals. The contribution of the cDC1 subset to the initiation of stress erythropoiesis was distinct from the well-recognized role of macrophages in supporting late erythroid maturation. Together, these findings offer insight into the mechanism of stress erythropoiesis and into disorders of erythrocyte generation associated with stress.

Anaerobic metabolism associated with traumatic hemorrhagic shock monitored by microdialysis of muscle tissue is dependent on the levels of hemoglobin and central venous oxygen saturation: a prospective, observational study

BackgroundTraumatic hemorrhagic shock resulting in tissue hypoxia is a significant cause of morbidity and mortality in polytraumatized patients. Early identification of tissue hypoxia is possible with microdialysis. The aim of this study was to determine the correlation between a marker of tissue hypoxia (L/P; lactate to pyruvate ratio) and selected parameters of systemic oxygen delivery (Hb; hemoglobin) and oxygen extraction (ScvO2; central venous oxygen saturation). We also investigated the severity of tissue hypoxia over the course of care.MethodsAdult patients with traumatic hemorrhagic shock were enrolled in this prospective, observational study. Microdialysis of the peripheral muscle tissue was performed. Demographic data and timeline of care were collected. Tissue lactate, pyruvate, glycerol, glucose levels, hemoglobin, serum lactate and oxygen saturation of the central venous blood (ScvO2) levels were also measured.ResultsThe L/P ratio trend may react to changes in systemic hemoglobin levels with a delay of 7 to 10 hours, particularly when systemic hemoglobin levels are increased by transfusion. Decrease in tissue L/P ratio may react to increase in ScvO2 with a delay of up to 10 hours, and such a decrease may signify elimination of tissue hypoxia after transfusion. We also observed changes in the L/P trend in the 13 hours preceding a change in the hemoglobin level. Fluid administration, which is routinely used as a first-line treatment of hypovolemic shock, can cause hemodilution and decreased hemoglobin. When ScvO2 decreases, increase in L/P ratio may precede the ScvO2 trend by 10 or 11 hours. An increase in the L/P ratio is an early warning sign of insufficient tissue oxygenation and should lead to intensive observation of hemoglobin levels, ScvO2 and other hemodynamic parameters. Patients who were treated more rapidly had lower maximal L/P values and a lower degree of tissue ischemia.ConclusionThe L/P ratio is useful to identify tissue ischemia and can estimate the effectiveness of fluid resuscitation. An increase in the L/P ratio is an early warning sign of inadequate tissue oxygenation and should lead to more detailed hemodynamic and laboratory monitoring. This information cannot usually be obtained from global markers.

New tools for optimizing fluid resuscitation in acute pancreatitis.

Acute pancreatitis (AP) is a frequent disease with degrees of increasing severity responsible for high morbidity. Despite continuous improvement in care, mortality remains significant. Because hypovolemia, together with microcirculatory dysfunction lead to poor outcome, fluid therapy remains a cornerstone of the supportive treatment. However, poor clinical evidence actually support the aggressive fluid therapy recommended in recent guidelines since available data are controversial. Fluid management remains unclear and leads to current heterogeneous practice. Different strategies may help to improve fluid resuscitation in AP. On one hand, integration of fluid therapy in a global hemodynamic resuscitation has been demonstrated to improve outcome in surgical or septic patients. Tailored fluid administration after early identification of patients with high-risk of poor outcome presenting inadequate tissue oxygenation is a major part of this strategy. On the other hand, new decision parameters have been developed recently to improve safety and efficiency of fluid therapy in critically ill patients. In this review, we propose a personalized strategy integrating these new concepts in the early fluid management of AP. This new approach paves the way to a wide range of clinical studies in the field of AP.

Peri‐operative oxygen use – the anaesthetist's perspective

The recent editorial by Decalmer & O'Driscoll 1 raised several issues that merit discussion. A significant proportion of the editorial presents data from studies reporting the harmful effects of excess oxygen. Although now accepted that careful titration of oxygen therapy in certain groups of patients can improve outcome, they represent a very different sub-set of patients to the majority undergoing anaesthesia and surgery. Therefore, the comparisons drawn may not be valid. No evidence is presented to support the claim that supplementary oxygen is likely to be of no benefit for the majority of patients in the immediate postoperative period. Furthermore, it is unknown whether avoiding supplementary oxygen at this time would actually lead to an increase in adverse events and patient harm. The 4th National Audit Project (NAP4) 2 and Difficult Airway Society guidelines 3 both highlight the potential for airway and breathing problems during the ‘immediate postoperative period’. Anaesthetists rely on an oxygen-rich functional residual capacity to allow time to deal safely with such problems. Doubtless, many patients' lives have been saved in this way. In addition, during this period, supplementary oxygen can be vital in preventing hypoxaemia due to hypoventilation induced by the respiratory depressant effects of anaesthetic drugs. In-line with the British Thoracic Society (BTS) guidelines 4, Decalmer & O'Driscoll's editorial focuses predominantly on targeting peripheral oxygen saturations (SpO2). This fails to highlight the importance of patient assessment in the postoperative period to determine the cause of hypoxaemia and commence appropriate treatment. A postoperative patient with a SpO2 of 94% would be acceptable according to BTS guidelines, but if this requires a FIO2 of 60% further assessment and intervention are required. Furthermore, if this patient has a haemoglobin of 6.0 g.dl−1, a SpO2 of 94% probably represents inadequate tissue oxygen delivery, which should be corrected by red cell transfusion. The editorial gives the impression that many postoperative patients are being harmed through excessive use of oxygen and that the focus should be on targeting SpO2. I do not believe that this is evidence-based.

Oxygen Therapy in Critical Illness

The management of hypoxemia in critically ill patients is challenging. Whilst the harms of tissue hypoxia are well recognized, the possibility of harm from excess oxygen administration, or other interventions targeted at mitigating hypoxemia, may be inadequately appreciated. The benefits of attempting to fully reverse arterial hypoxemia may be outweighed by the harms associated with high concentrations of supplemental oxygen and invasive mechanical ventilation strategies. We propose two novel related strategies for the management of hypoxemia in critically ill patients. First, we describe precise control of arterial oxygenation involving the specific targeting of arterial partial pressure of oxygen or arterial hemoglobin oxygen saturation to individualized target values, with the avoidance of significant variation from these levels. The aim of precise control of arterial oxygenation is to avoid the harms associated with inadvertent hyperoxia or hypoxia through careful and precise control of arterial oxygen levels. Secondly, we describe permissive hypoxemia: the acceptance of levels of arterial oxygenation lower than is conventionally tolerated in patients. The aim of permissive hypoxemia is to minimize the possible harms caused by restoration of normoxemia while avoiding tissue hypoxia. This review sets out to discuss the strengths and limitations of precise control of arterial oxygenation and permissive hypoxemia as candidate management strategies in hypoxemic critically ill patients. We searched PubMed for references to "permissive hypoxemia/hypoxaemia" and "precise control of arterial oxygenation" as well as reference to "profound hypoxemia/hypoxaemia/hypoxia," "severe hypoxemia/hypoxaemia/hypoxia." We searched personal reference libraries in the areas of critical illness and high altitude physiology and medicine. We also identified large clinical studies in patients with critical illness characterized by hypoxemia such as acute respiratory distress syndrome. Studies were selected that explored the physiology of hypoxemia in healthy volunteers or critically ill patients. The data were subjectively assessed and combined to generate the narrative. Inadequate tissue oxygenation and excessive oxygen administration can be detrimental to outcome but safety thresholds lack definition in critically ill patients. Precise control of arterial oxygenation provides a rational approach to the management of arterial oxygenation that reflects recent clinical developments in other settings. Permissive hypoxemia is a concept that is untested clinically and requires robust investigation prior to consideration of implementation. Both strategies will require accurate monitoring of oxygen administration and arterial oxygenation. Effective, reliable measurement of tissue oxygenation along with the use of selected biomarkers to identify suitable candidates and monitor harm will aid the development of permissive hypoxemia as viable clinical strategy. Implementation of precise control of arterial oxygenation may avoid the harms associated with excessive and inadequate oxygenation. However, at present there is no direct evidence to support the immediate implementation of permissive hypoxemia and a comprehensive evaluation of its value in critically ill patients should be a high research priority.

Invited Commentary

In this article, Bhat and colleagues [1Bhat P. Hirsch J.C. Gelehrter S. et al.Outcomes of infants weighing three kilograms or less requiring extracorproeal membrane oxygenation after cardiac surgery.Ann Thorac Surg. 2013; 95: 656-662Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar] report on the survival of low-birth-weight (LBW) neonates weighing ≤3 kg (median gestational age 38 weeks) supported with extracorporeal membrane oxygenation (ECMO) after corrective or palliative cardiac surgical procedures for congenital heart disease at their institution. They report a 30-day post-ECMO decannulation survival of 33%. Survival in their cohort is lower than the 40% survival reported by the Extracorporeal Life Support Organization's data registry for all neonates supported with ECMO for cardiac indications, the 53% survival for LBW infants (<2 kg) supported with ECMO for respiratory failure, and survival for late preterm infants (34 to 36 weeks gestation) with respiratory failure supported with ECMO (mortality, 26.2%) [2International Summary 2012 of the Extracorporeal Life Support Organization.http://www.elso-net.orgGoogle Scholar, 3Rozmiarek A.J. Qureshi F.G. Cassidy L. et al.How low can you go? Effectiveness and safety of extracorporeal membrane oxygenation in low-birth-weight neonates.J Pediatr Surg. 2004; 39: 845-847Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 4Ramachandrappa A. Rosenberg E.S. Wagoner S. Jain L. Morbidity and mortality in late preterm infants with severe hypoxic respiratory failure on extra-corporeal membrane oxygenation.J Pediatr. 2011; 159: 192-198.e3Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar]. Mortality in this cohort was associated with the need for renal replacement therapy, indicating that the onset of end-organ dysfunction increased the risk of mortality [1Bhat P. Hirsch J.C. Gelehrter S. et al.Outcomes of infants weighing three kilograms or less requiring extracorproeal membrane oxygenation after cardiac surgery.Ann Thorac Surg. 2013; 95: 656-662Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar]. The authors do not separately report on the incidence of neurologic complications but state that the incidence of nonrenal complications, including neurologic events, was low. This may be due to the more mature gestational age of the neonates in this cohort. Another important finding in this study is the high mortality rate in patients needing recannulation after a trial of removal from ECMO had been unsuccessful, indicating that repeated ECMO may not improve survival. Although the amount of inotrope support used before ECMO and during the first 48 hours was not different between survivors and nonsurvivors, there was a trend toward increased lactate levels after 24 hours of ECMO support in nonsurvivors. Nonresolution of lactate acidosis during ECMO may indicate severe cardiorespiratory dysfunction before and during ECMO, or inadequate tissue oxygen delivery from inadequate ECMO support. Continued lactic acidosis after the initiation of ECMO support should prompt investigation into causes of inadequate support, including mechanical limitations that can arise from ECMO technology. In LBW neonates, body size may limit the provision of adequate ECMO flows (eg, limitations in cannula size imposed by the small vessels available for ECMO cannulation) and may result in inadequate ECMO support. Given that an increasing number of preterm and LBW neonates are undergoing complex corrective or palliative congenital heart surgical procedures, and that some of these patients may need postoperative ECMO support, future research should be focused on improving ECMO technology and our knowledge of patient management issues for premature and LBW infants supported with ECMO to help improve their outcomes. Outcomes of Infants Weighing Three Kilograms or Less Requiring Extracorporeal Membrane Oxygenation After Cardiac SurgeryThe Annals of Thoracic SurgeryVol. 95Issue 2PreviewExtracorporeal membrane oxygenation (ECMO) is the most common form of cardiac support for postcardiotomy cardiac failure in children. While its benefits have been thoroughly explored in infants weighing more than 3kg, similar analyses are lacking in lower weight neonates. This single-center study investigated outcomes and risks for poor survival among infants weighing 3 kg or less. Full-Text PDF

Clinical use of lactate monitoring in critically ill patients

Increased blood lactate levels (hyperlactataemia) are common in critically ill patients. Although frequently used to diagnose inadequate tissue oxygenation, other processes not related to tissue oxygenation may increase lactate levels. Especially in critically ill patients, increased glycolysis may be an important cause of hyperlactataemia. Nevertheless, the presence of increased lactate levels has important implications for the morbidity and mortality of the hyperlactataemic patients. Although the term lactic acidosis is frequently used, a significant relationship between lactate and pH only exists at higher lactate levels. The term lactate associated acidosis is therefore more appropriate. Two recent studies have underscored the importance of monitoring lactate levels and adjust treatment to the change in lactate levels in early resuscitation. As lactate levels can be measured rapidly at the bedside from various sources, structured lactate measurements should be incorporated in resuscitation protocols.

Lactate Clearance in the Acutely Traumatized Patient

Lactate Clearance in the Acutely Traumatized Patient

Hemodynamic Monitoring in the Intensive Care Unit

Patients in the intensive care unit are often critically ill with inadequate tissue perfusion and oxygenation. This inadequate delivery of substrates at the cellular level is a common definition of shock. Hemodynamic monitoring is the observation of cardiovascular physiology. The purpose of hemodynamic monitoring is to identify abnormal physiology and intervene before complications, including organ failure and death, occur. The most common types of invasive hemodynamic monitors are central venous catheters, pulmonary artery catheters, and arterial pulse-wave analysis. Ultrasonography is a noninvasive alternative being used in intensive care units for hemodynamic measurements and assessments.

Detection of Microregional Hypoxia in Mouse Cerebral Cortex by Two-photon Imaging of Endogenous NADH Fluorescence

The brain's ability to function at high levels of metabolic demand depends on continuous oxygen supply through blood flow and tissue oxygen diffusion. Here we present a visualized experimental and methodological protocol to directly visualize microregional tissue hypoxia and to infer perivascular oxygen gradients in the mouse cortex. It is based on the non-linear relationship between nicotinamide adenine dinucleotide (NADH) endogenous fluorescence intensity and oxygen partial pressure in the tissue, where observed tissue NADH fluorescence abruptly increases at tissue oxygen levels below 10 mmHg1. We use two-photon excitation at 740 nm which allows for concurrent excitation of intrinsic NADH tissue fluorescence and blood plasma contrasted with Texas-Red dextran. The advantages of this method over existing approaches include the following: it takes advantage of an intrinsic tissue signal and can be performed using standard two-photon in vivo imaging equipment; it permits continuous monitoring in the whole field of view with a depth resolution of ~50 μm. We demonstrate that brain tissue areas furthest from cerebral blood vessels correspond to vulnerable watershed areas which are the first to become functionally hypoxic following a decline in vascular oxygen supply. This method allows one to image microregional cortical oxygenation and is therefore useful for examining the role of inadequate or restricted tissue oxygen supply in neurovascular diseases and stroke.

Detection of Microregional Hypoxia in Mouse Cerebral Cortex by Two-photon Imaging of Endogenous NADH Fluorescence

The brain's ability to function at high levels of metabolic demand depends on continuous oxygen supply through blood flow and tissue oxygen diffusion. Here we present a visualized experimental and methodological protocol to directly visualize microregional tissue hypoxia and to infer perivascular oxygen gradients in the mouse cortex. It is based on the non-linear relationship between nicotinamide adenine dinucleotide (NADH) endogenous fluorescence intensity and oxygen partial pressure in the tissue, where observed tissue NADH fluorescence abruptly increases at tissue oxygen levels below 10 mmHg1. We use two-photon excitation at 740 nm which allows for concurrent excitation of intrinsic NADH tissue fluorescence and blood plasma contrasted with Texas-Red dextran. The advantages of this method over existing approaches include the following: it takes advantage of an intrinsic tissue signal and can be performed using standard two-photon in vivo imaging equipment; it permits continuous monitoring in the whole field of view with a depth resolution of ~50 μm. We demonstrate that brain tissue areas furthest from cerebral blood vessels correspond to vulnerable watershed areas which are the first to become functionally hypoxic following a decline in vascular oxygen supply. This method allows one to image microregional cortical oxygenation and is therefore useful for examining the role of inadequate or restricted tissue oxygen supply in neurovascular diseases and stroke.

Association between intraoperative tissue oxygenation, arterial blood pressure and noradrenaline use in urological patients

Background and Goal of Study: Inadequate tissue oxygenation should be prevented during surgery as it might cause postoperative morbidity. In this observational study we looked at factors that might influence tissue oxygenation (StO2) such as blood pressure and use of vasoactive drugs. Materials and Methods: In 159 urological patients receiving balanced anaesthesia and mechanical ventilation, we measured StO2 intraoperatively on the thenar eminescence (InSpectra, Hutchinson Tech., USA) along with (non)invasive blood pressure and recorded the use of noradrenaline. We correlated StO2 and MAP as recorded at defined moments during surgery. In addition, we looked at the effects of low blood pressure (as defined by the areas under the curve (AUC) while MAP was < 65 mmHg) on StO2. Furthermore, we related StO2 to different noradrenaline (NA) dosages: none, low (<0.03 mg/kg/min) and high dose (≥0.03 mg/kg/min). Results and Discussion: At the start and end of surgery, there was no correlation between StO2 and MAP. However, the lowest recorded MAP per patient did correlate with the corresponding StO2 (R=0.206, R2=0.043, p< 0.01; Pearson‘s correlation, 2-tailed). Similarly, a higher MAP AUC < 65 mmHg was associated with a lower average StO2 (R=-0.189, R2=0.036, p< 0.05; Spearman‘s correlation, 2-tailed). These results support the hypothesis of intact autoregulation of tissue blood flow to preserve StO2 in the normal range of blood pressure, whereas this autoregulation fails during lowest pressures. Furthermore, StO2 was higher without noradrenaline (no NA)(88.4%) than during high dose noradrenaline (85.2%) (p< 0.001; ANOVA, Bonferroni post hoc analysis). Possibly, the vasoconstrictive effect of noradrenaline decreases blood flow through the observed tissue (peripheral muscle). Conclusions: Tissue oxygenation is not influenced by blood pressure in the normal blood pressure range during anaesthesia, whereas it becomes dependent when MAP drops below the clinically relevant threshold of 65 mmHg. Noradrenaline use is associated with a decreased tissue oxygenation in the thenar eminescence. Further studies should identify other factors that may influence tissue oxygenation and assess the impact of tissue hypoxia on postoperative patients‘ outcome.

P-16 Assessment of muscle oxygen saturation in the early phase of extracorporeal life support

Introduction. Patients with extracorporeal life support (ECLS) may be at risk of inadequate tissue perfusion and oxygenation that leads to multiple-organ dysfunction. Near-infrared spectroscopy has emerged in recent years as a non-invasive tool for monitoring peripheral oxygenation (StO2) in various tissues, including muscle. Using a dynamic vascular occlusive test (VOT), StO2 abnormalities were identified during septic shock and severe trauma, suggesting microvascular dysfunction [1-3]. We wondered whether StO2 abnormalities could exist during the early phase of ECLS.

A new fibre optic pulse oximeter probe for monitoring splanchnic organ arterial blood oxygen saturation

A new, continuous method of monitoring splanchnic organ oxygen saturation (SpO2) would make the early detection of inadequate tissue oxygenation feasible, reducing the risk of hypoperfusion, severe ischaemia, and, ultimately, death. In an attempt to provide such a device, a new fibre optic based reflectance pulse oximeter probe and processing system were developed followed by an in vivo evaluation of the technology on seventeen patients undergoing elective laparotomy. Photoplethysmographic (PPG) signals of good quality and high signal-to-noise ratio were obtained from the small bowel, large bowel, liver and stomach. Simultaneous peripheral PPG signals from the finger were also obtained for comparison purposes. Analysis of the amplitudes of all acquired PPG signals indicated much larger amplitudes for those signals obtained from splanchnic organs than those obtained from the finger. Estimated SpO2 values for splanchnic organs showed good agreement with those obtained from the finger fibre optic probe and those obtained from a commercial device. These preliminary results suggest that a miniaturized ‘indwelling’ fibre optic sensor may be a suitable method for pre-operative and post-operative evaluation of splanchnic organ SpO2 and their health.

An In Vivo Investigation of Photoplethysmographic Signals and Preliminary Pulse Oximetry Estimation from the Bowel Using a New Fiberoptic Sensor

The continuous monitoring of splanchnic organ oxygen saturation could make the early detection of inadequate tissue oxygenation feasible, reducing the risk of hypoperfusion, severe ischemia, multiple organ failure, and, ultimately, death. Current methods for assessing splanchnic perfusion have not been widely accepted for use in the clinical care environment. In an attempt to overcome the limitations of the current techniques, a new fiberoptic photoplethysmographic (PPG)/pulse oximetry sensor was developed as a means of assessing splanchnic organ perfusion during surgery in humans. A new fiberoptic splanchnic pulse oximeter and an optically identical fiberoptic finger pulse oximeter have been developed. Simultaneous PPG signals and preliminary estimates of arterial oxygen saturation from the bowel (small and large) and finger were obtained in 17 patients (3 men and 14 women) undergoing open laparotomy. Good quality PPG signals were obtained from the small and large bowel and from the finger in all patients (lower 95% confidence limit for the proportion was 0.64). Comparisons of blood oxygen saturation values acquired when using the splanchnic and the finger fiberoptic sensors and a commercial finger pulse oximeter indicated that there was no statistically significant difference between them (all P>0.454). A Bland and Altman plot of the difference between blood oxygen saturation values from the bowel fiberoptic pulse oximeter and the fiberoptic finger pulse oximeter against their mean showed that the limits of agreement between the 2 pulse oximeters were -3.8% and 4.2% for small bowel measurements, and -3.4% and 4.3% for large bowel measurements. The 95% prediction interval for the difference between the 2 devices was between -4.2% and 4.7%. This study demonstrated that good quality PPG signals can be obtained from the bowel using a new fiberoptic sensor. Further evaluation is required to determine whether fiberoptic pulse oximetry of the bowel may provide a suitable method for monitoring splanchnic perfusion.

Muscle StO2 in critically ill patients

Tissue hypoperfusion is a common pathophysiologic process leading to multiple-organ dysfunction and death. An important goal of hemodynamic monitoring is the early detection of inadequate tissue perfusion and oxygenation. The use of simple, noninvasive monitoring techniques has the advantage of facilitating earlier initiation of therapy. Near-infrared spectroscopy has emerged in recent years as a tool for monitoring peripheral oxygenation (StO2) in various tissues, including muscle. Here, we review our current knowledge about the applicability, usefulness, and limitations of near-infrared spectroscopy as a technique to evaluate muscle oxygenation in acutely ill patients. StO2 may be an appropriate measure for early resuscitation of critically ill patients, especially in those with low cardiac output states or after severe trauma. Its usefulness in sepsis is less well established. However, by inducing an occlusion stress, a variety of dynamic variables can be measured to assess local metabolic demand and microvascular reactivity. Several recent studies have shown that profound alterations of these near-infrared-spectroscopy-derived dynamic variables are frequent in patients with severe sepsis and these alterations are associated with a poor outcome. Near-infrared spectroscopy provides a noninvasive measure of muscle oxygen metabolism and microvascular dysfunction in critically ill patients. It may be useful to guide the management of critically ill patients.

Norepinephrine to increase blood pressure in endotoxaemic pigs is associated with improved hepatic mitochondrial respiration

IntroductionLow blood pressure, inadequate tissue oxygen delivery and mitochondrial dysfunction have all been implicated in the development of sepsis-induced organ failure. This study evaluated the effect on liver mitochondrial function of using norepinephrine to increase blood pressure in experimental sepsis.MethodsThirteen anaesthetized pigs received endotoxin (Escherichia coli lipopolysaccharide B0111:B4; 0.4 μg/kg per hour) and were subsequently randomly assigned to norepinephrine treatment or placebo for 10 hours. Norepinephrine dose was adjusted at 2-hour intervals to achieve 15 mmHg increases in mean arterial blood pressure up to 95 mmHg. Systemic (thermodilution) and hepatosplanchnic (ultrasound Doppler) blood flow were measured at each step. At the end of the experiment, hepatic mitochondrial oxygen consumption (high-resolution respirometry) and citrate synthase activity (spectrophotometry) were assessed.ResultsMean arterial pressure (mmHg) increased only in norepinephrine-treated animals (from 73 [median; range 69 to 81] to 63 [60 to 68] in controls [P = 0.09] and from 83 [69 to 93] to 96 [86 to 108] in norepinephrine-treated animals [P = 0.019]). Cardiac index and systemic oxygen delivery (DO2) increased in both groups, but significantly more in the norepinephrine group (P < 0.03 for both). Cardiac index (ml/min per·kg) increased from 99 (range: 72 to 112) to 117 (110 to 232) in controls (P = 0.002), and from 107 (84 to 132) to 161 (147 to 340) in norepinephrine-treated animals (P = 0.001). DO2 (ml/min per·kg) increased from 13 (range: 11 to 15) to 16 (15 to 24) in controls (P = 0.028), and from 16 (12 to 19) to 29 (25 to 52) in norepinephrine-treated animals (P = 0.018). Systemic oxygen consumption (systemic VO2) increased in both groups (P < 0.05), whereas hepatosplanchnic flows, DO2 and VO2 remained stable. The hepatic lactate extraction ratio decreased in both groups (P = 0.05). Liver mitochondria complex I-dependent and II-dependent respiratory control ratios were increased in the norepinephrine group (complex I: 3.5 [range: 2.1 to 5.7] in controls versus 5.8 [4.8 to 6.4] in norepinephrine-treated animals [P = 0.015]; complex II: 3.1 [2.3 to 3.8] in controls versus 3.7 [3.3 to 4.6] in norepinephrine-treated animals [P = 0.09]). No differences were observed in citrate synthase activity.ConclusionNorepinephrine treatment during endotoxaemia does not increase hepatosplanchnic flow, oxygen delivery or consumption, and does not improve the hepatic lactate extraction ratio. However, norepinephrine increases the liver mitochondria complex I-dependent and II-dependent respiratory control ratios. This effect was probably mediated by a direct effect of norepinephrine on liver cells.

Comparison Of Autologous Vs Homologous Blood Transfusion Combined With Acute Normovolemic Hemodilution And Hypotensive Anaesthesia In Spine Surgeries

Comparison Of Autologous Vs Homologous Blood Transfusion Combined With Acute Normovolemic Hemodilution And Hypotensive Anaesthesia In Spine Surgeries

Tissue oxygen saturation and the rate of tissue deoxygenation during stagnant ischemia in the medical emergency department

Early recognition of patients with inadequate tissue oxygenation facilitates early diagnostic evaluation and treatment that was correlated with improved outcome. Near-infrared spectroscopy is noninvasive and in the emergency setting is a rapidly appliable method for measuring StO2.

Mixed venous oxygen saturation cannot be estimated by central venous oxygen saturation in septic shock: reply to Dr. Bourdeaux

Sir: We thank Dr. Bourdeaux for his interest in our study. We showed that during the first day in the intensive care unit (ICU), the average difference between ScvO2 and SvO2 values in patients with septic shock was 4%, but the individual differences varied from –8% to +17% [1]. Dr. Bourdeaux highlighted two issues that we would like to discuss: first, the correlation and the clinical interchangeability of SvO2 and ScvO2, and second, the importance of the sampling site. As Dr. Bourdeaux pointed out, SvO2 and ScvO2 values correlate well, which is not a surprise, because SvO2 is a mixture of ScvO2, saturation of inferior vena cava, and saturation of coronary sinus, blended according to the proportional blood flow. In addition, SvO2 and ScvO2 share the same determinants (SaO2, cardiac output, and haemoglobin concentration). Inevitably, therefore, there exists a clear causality between these two parameters. However, we would like to question the clinical relevance of correlation between these two parameters. We re-evaluated our data concerning possible clinical interventions according to saturation values. In a previous study we had shown that SvO2 values < 70% increased the risk of mortality in septic shock [2]. According to the present data, 16% of SvO2 values were below 70% while ScvO2 was above 70%. If we then assume that SvO2 over 65% and ScvO2 over 70% are clinically acceptable, treatment decisions would still have been different in 14% of measurements (either SvO2 below 65% with ScvO2 over 70% or SvO2 over 65% with ScvO2 below 70%). Another important issue in ScvO2 monitoring is where the tip of the central venous pressure catheter is located. The saturation values in shock are lower in right atrium and in inferior vena cava than in superior vena cava [3, 4]. Dr. Bourdeaux considered that as an advantage, but we feel that the uncertainty in ScvO2 monitoring may lead to false interpretation of the results and to overtreatment by unnecessary pushing of haemodynamics with vasoactive medication. We conclude that ScvO2 and SvO2 are neither equal nor interchangeable. However, is ScvO2 clinically useful “per se” in monitoring of global tissue oxygenation in sepsis or septic shock during ICU stay? Unfortunately, to the best of our knowledge the value of ScvO2 during the ICU stay as a target of haemodynamic treatment, or as a predictor of hospital mortality, has not been investigated. The generalisation of the results of the landmark study by Rivers et al. [5] from the emergency department to the ICU is, in any case, not appropriate. Although low ScvO2 is always a sign of globally insufficient tissue oxygenation, the problem still exists with normal ScvO2, by which we cannot rule out inadequate tissue oxygenation in septic shock. SvO2 is more sensitive for that purpose. References