In JoVE (1)

Other Publications (132)

Articles by Stephan M. Jakob in JoVE

Other articles by Stephan M. Jakob on PubMed

ARDS. Monitoring Tissue Perfusion

Critical Care Clinics. Jan, 2002  |  Pubmed ID: 11910727

A clinically feasible method for assessing regional splanchnic perfusion is still lacking. Methods used for research purposes demonstrate that the effects of current therapies on splanchnic perfusion are not predictable in intensive care patients with and without ARDS. Tonometry, laser Doppler flowmetry, and spectrophotometry have been used to assess splanchnic perfusion. Combining the available methods in different parts of the gastrointestinal tract may help assess splanchnic perfusion more accurately in the near future.

Effect of Dopamine-induced Changes in Splanchnic Blood Flow on MEGX Production from Lidocaine in Septic and Cardiac Surgery Patients

Shock (Augusta, Ga.). Jul, 2002  |  Pubmed ID: 12095126

The production of monoethylglycine xylidide (MEGX) from lidocaine is thought to be dependent on hepatic blood flow. We assessed the relationship between hepatosplanchnic blood flow, lidocaine uptake, and the production of MEGX from lidocaine in seven patients after cardiac surgery and in nine septic patients. Systemic (pulmonary artery catheter) and splanchnic (hepatic vein catheter and dye dilution) hemodynamics and arterial and hepatic venous lidocaine and MEGX concentrations were measured after a lidocaine bolus injection (1 mg/kg) before and 90 min after increasing cardiac output by at least 25% with dopamine. Dopamine infusion [in cardiac surgery patients 4.2 (1.4-8.5) microg x kg(-1) x min(-1) (median, range) and in septic patients 4.0 (2.1-9.0) microg x kg(-1) x min(-1)] increased splanchnic blood flow in cardiac surgery patients from 0.65 (0.12) L x min(-1) x m(-2) to 0.84 (0.14) L x min(-1) x m(-2) mean (standard deviation) P = 0.018) and in septic patients from 0.91 (0.32) L x min(-1) x m(-2) to 1.12 (0.40) L x min(-1) x m(-2) (P = 0.038). Splanchnic MEGX production for the 30 min after lidocaine injection was higher in cardiac surgery patients than in septic patients both at baseline [4130 (1100) microg x m(-2) vs. 930 (420) microg x m(-2) (P < 0.005)] and afterdopamine infusion [4480 (1000) microg x m(-2) vs. 1090 (620) microg x m(-2) (P = 0.005)]. We found no correlation between changes in MEGX production and changes in splanchnic blood flow. Patients with sepsis have severe impairment of cytochrome P450-dependent liver function, which is not influenced by acute changes in hepatosplanchnic blood flow. MEGX production cannot be used as an estimate of changes in splanchnic blood flow.

Effects of Dopamine on Systemic and Regional Blood Flow and Metabolism in Septic and Cardiac Surgery Patients

Shock (Augusta, Ga.). Jul, 2002  |  Pubmed ID: 12095139

Dopamine is used in the clinical setting to support cardiac output and blood pressure and to improve diuresis. Experimental studies suggest that dopamine may reduce splanchnic perfusion and redistribute blood flow locally. To assess the effects of dopamine on splanchnic perfusion, we used dopamine to increase cardiac output by 25% in nine septic patients and 11 patients after cardiac surgery. Systemic (pulmonary artery catheter) and splanchnic (hepatic vein catheter and dye dilution) hemodynamics and oxygen transport were measured at baseline and 90 min after increasing the cardiac output. Dopamine infusion [in cardiac surgery patients 4.2 (1.4-8.5) microg x kg(-1) x min(-1) (median, range) and in septic patients 4.0 (2.1-9.0) microg x kg(-1) x min(-1)] increased splanchnic blood flow in cardiac surgery patients from 0.61 (0.13) L x min(-1) x m(-2) to 0.82 (0.13) L x min(-1) x m(-2) [mean (standard deviation; SD); P = 0.018] and in septic patients from 0.91 (0.32) L x min(-1) x m(-2) to 1.12 (0.40) L x min(-1) x m(-2) (P = 0.038). Splanchnic oxygen consumption increased in cardiac surgery patients from 39 (5) mL x min(-1) x m(-2) to 46 (6) mL x min(-1) x m(-2) (P = 0.003) but decreased in septic patients from 61 (19) mL x min(-1) x m(-2) to 51 (17) L x min(-1) x m(-2) (p = 0.021). Because of the unexpected results, we compared these data post hoc with data obtained from another group of 15 septic patients with acute lung injury, where dobutamine was used to increase cardiac output in a similar design. Dobutamine in these patients [6.4 (4.2-9.5) microg x kg(-1) x min(-1)] increased splanchnic blood flow from 1.20 (0.44) L x min(-1) x m(-2) to 1.43 (0.57) L x min(-1) x m(-2) (P = 0.008), while splanchnic oxygen consumption did not change 72 (25) mL x min(-1) x m(-2) vs. 76 (22) mL x min(-1) x m(-2) (not significant)]. The reduction of splanchnic oxygen consumption by dopamine in sepsis suggests an impairment of hepatosplanchnic metabolism despite an increase in regional perfusion. The safety and indications of dopamine use in sepsis should be re-evaluated.

Splanchnic Vasoregulation During Mesenteric Ischemia and Reperfusion in Pigs

Shock (Augusta, Ga.). Aug, 2002  |  Pubmed ID: 12166777

We evaluated the hepatic arterial buffer response (HABR) to portal vein (PV) occlusion during 2 h of reduced superior mesenteric arterial blood flow (median 2 mL min(-1) kg(-1), range of 1-3 mL min(-1) kg(-1)) and 1 h of reperfusion in seven pigs and in seven controls. In animals with reduced mesenteric blood flow, celiac trunk blood flow (Qtr) increased during mesenteric hypoperfusion from 4 +/- 1 mL min(-1) kg(-1) (mean +/- SD) to 16 +/- 3 mL min(-1) kg(-1) (P = 0.028), and hepatic arterial blood flow (Qha) increased from 2 +/- 1 to 10 +/- 4 mL min(-1) kg(-1) (P= 0.018). The extra-hepatic fraction of Qtr (Qtr-Qha) also increased (P = 0.028). In controls, Qtr and Qha also increased, but to lower levels. At baseline, acute PV occlusion increased Qha by 5.0 +/- 2.8 mL min(-1) kg(-1) (P < 0.001), whereas Qtr-Qha decreased by 1.6 +/- 1.6 mL min(-1) kg(-1) (P = 0.007). After 120 min of reduced mesenteric blood flow, the HABR was exhausted (change in Qha to PV occlusion of 0.7 +/- 1.6 mL min(-1) kg(-1) [P= 0.27]). The efficacy of the HABR was also reduced in controls animals. Despite increased cardiac output, all flows from the celiac trunk decreased during reperfusion (P = 0.028) and the HABR partially recovered. We conclude that reduced mesenteric perfusion impairs the HABR, which recovers only partially after reperfusion. The distribution of the increased celiac trunk flow secondary to PV occlusion ranges from increased HABR and decreased non-hepatic blood flow (a steal) to decreased hepatic arterial blood flow and increased non-hepatic blood flow (an inverse steal).

Acute Normovolemic Hemodilution Improves Oxygenation in Ischemic Flap Tissue

Anesthesiology. Jun, 2002  |  Pubmed ID: 12170063

The flaps used in reconstructive surgery are prone to ischemia and hypoxia, which imply a considerable risk of wound-healing complications. During normovolemic hemodilution, the oxygenation may further deteriorate because of the lack of erythrocytes or improve because of increased microcirculatory blood flow. The aim of this study was to investigate the net effect of normovolemic hemodilution of various degrees on the microcirculation and oxygenation in ischemic flap tissue in adult minipigs.

Clinical Review: Splanchnic Ischaemia

Critical Care (London, England). Aug, 2002  |  Pubmed ID: 12225604

Inadequate splanchnic perfusion is associated with increased morbidity and mortality, particularly if liver dysfunction coexists. Heart failure, increased intra-abdominal pressure, haemodialysis and the presence of obstructive sleep apnoea are among the multiple clinical conditions that are associated with impaired splanchnic perfusion in critically ill patients. Total liver blood flow is believed to be relatively protected when gut blood flow decreases, because hepatic arterial flow increases when portal venous flow decreases (the hepatic arterial buffer response [HABR]). However, there is evidence that the HABR is diminished or even abolished during endotoxaemia and when gut blood flow becomes very low. Unfortunately, no drugs are yet available that increase total hepato-splanchnic blood flow selectively and to a clinically relevant extent. The present review discusses old and new concepts of splanchnic vasoregulation from both experimental and clinical viewpoints. Recently published trials in this field are discussed.

Splanchnic Blood Flow in Low-flow States

Anesthesia and Analgesia. Apr, 2003  |  Pubmed ID: 12651672

Insufficient splanchnic blood flow in critically ill patients is the result of a multitude of different diseases, treatment modalities and their interplay, and is associated with increased morbidity and mortality. A combination of diminished and heterogeneous mesenteric blood flow, impaired or exhausted regulatory mechanisms and adverse drug effects may coexist with normal systemic hemodynamics.

Change in Stroke Volume in Response to Fluid Challenge: Assessment Using Esophageal Doppler

Intensive Care Medicine. Oct, 2003  |  Pubmed ID: 12684746

To compare two methods of assessing a change in stroke volume in response to fluid challenge: esophageal Doppler and thermodilution with the pulmonary artery catheter.

Apparent Heterogeneity of Regional Blood Flow and Metabolic Changes Within Splanchnic Tissues During Experimental Endotoxin Shock

Anesthesia and Analgesia. Aug, 2003  |  Pubmed ID: 12873953

We conducted a randomized, controlled experiment of prolonged lethal endotoxin shock in pigs aiming at 1) simultaneously measuring perfusion at different parts of the gut to study the potential heterogeneity of blood flow within the splanchnic region; 2) studying the association among regional blood flows, oxygen supply, and different metabolic markers of perfusion; and 3) analyzing the association between histological gut injury and markers of perfusion and metabolism. The primary response to endotoxin was a decrease in systemic and splanchnic blood flow followed by hyperdynamic systemic circulation. Redistribution of blood flows occurred within the splanchnic circulation: superior mesenteric artery blood flow was maintained, whereas celiac trunk blood flow was compromised. Mucosal to arterial PCO(2) gradients did not reflect changes in total splanchnic perfusion, but they were associated with regional blood flows during the hypodynamic phase of shock. During hyperdynamic systemic circulation, PCO(2) gradients increased heterogeneously in the gastrointestinal tract, whereas luminal lactate increased only in the colon. Histological analysis revealed mucosal epithelial injury only in the colon. We conclude that markers of perfusion and metabolism over one visceral region do not reflect perfusion and metabolism in other splanchnic vascular areas. Intestinal mucosal epithelial injury occurs in the colon during 12 h of endotoxin shock while the epithelial injury is still absent in the jejunum. Hyperdynamic and hypotensive shock induces gut luminal lactate release in the colon but not in the jejunum. The association or causality between the mucosal epithelial injury and luminal lactate release remains to be elucidated.

Changes in Regional Blood Flow and PCO(2) Gradients During Isolated Abdominal Aortic Blood Flow Reduction

Intensive Care Medicine. Dec, 2003  |  Pubmed ID: 13680116

pCO(2) gradients are used for the assessment of splanchnic regional and local mucosal blood flow changes in experimental and clinical research. pCO(2) gradients may not parallel blood flow changes because of concomitant changes in metabolism, hemoglobin, temperature, and the Haldane effect.

Diagnosis and Management of Electrolyte Emergencies

Best Practice & Research. Clinical Endocrinology & Metabolism. Dec, 2003  |  Pubmed ID: 14687593

Electrolyte and fluid imbalances are disorders frequently observed in critical care patients. In many instances patients are asymptomatic, but they may also present with neurological alterations, severe muscle weakness, nausea and vomiting or cardiovascular emergencies. Therefore, a pathophysiological understanding of these disorders is necessary for initiating an appropriate therapy. After a precise history-including drug prescriptions-has been obtained from the patient or his/her relatives, determination of the hydration status of the patient and measurement of acid-base status, plasma and urine osmolality and electrolytes are the first steps in the assessment of the disease. Once a diagnosis has been established, great attention has to be paid to the rate at which the disorder is corrected because this-if inappropriate-may cause more severe damage to the patient than the disease itself. This chapter addresses the initial diagnostic and therapeutic steps of the most common electrolyte emergencies.

Changes in Splanchnic Circulation During an Alveolar Recruitment Maneuver in Healthy Porcine Lungs

Anesthesia and Analgesia. May, 2004  |  Pubmed ID: 15105226

Recruitment maneuvers (RM) are advocated as a complement to mechanical ventilation during anesthesia and in acute lung injury. However, they produce high intrathoracic pressures and volumes that may compromise hemodynamics. Our aim was to analyze the effect of a RM on hemodynamics in 10 anesthetized pigs. We assessed carotid, pulmonary, femoral, and hepatic arterial pressures, hepatic and portal venous pressures, total splanchnic (celiac trunk + superior mesenteric artery), hepatic, splenic, renal, and carotid arterial flows, and portal venous flow. We recorded hemodynamics, respiratory mechanics and blood gases before and at 8 min after RM (sustained inflation to 40 cm H(2)O of airway pressure lasting 20 s). Hemodynamics were also measured during RM, and at 1, 3, and 5 min after RM. All flows (P = 0.030) and arterial pressures (P < or = 0.048) decreased during RM, whereas venous pressures increased (P = 0.030). Flows and pressures returned to 75%-109% of baseline immediately after RM. Total splanchnic, renal and portal flows remained decreased at 8 min after RM (P < or = 0.042). Oxygenation did not change, and respiratory mechanics improved after the RM. RM produced a marked, though transitory, impairment of blood flow in all studied vessels. Despite prompt partial recovery, total splanchnic circulation remained reduced at 8 min after RM. This residual decrease may present a risk in conditions with markedly compromised circulatory reserves.

Measuring Depth of Sedation with Auditory Evoked Potentials During Controlled Infusion of Propofol and Remifentanil in Healthy Volunteers

Anesthesia and Analgesia. Dec, 2004  |  Pubmed ID: 15562062

Avoiding excessively deep levels of sedation is a major problem in intensive care patients. We studied whether clinically relevant levels of sedation can be objectively assessed using long latency auditory evoked potentials. We measured the auditory evoked potentials at 100 ms after the stimulus (N100) in 10 healthy volunteers during stepwise increasing, clinically relevant levels of sedation (Ramsay score [RS] 2-4). The volunteers were studied on three separate occasions and received an infusion of either propofol or a combination of propofol and remifentanil. Effects of remifentanil infusion alone were tested during target controlled infusion (target plasma concentrations: 1, 2, and 3 ng/mL). Remifentanil did not affect evoked potential amplitudes and latencies. During both propofol-induced and propofol/remifentanil-induced sedation, the N100 amplitude decreased similarly without an effect on the latencies as the level of sedation increased from Ramsay score 2 to Ramsay score 4 (P < 0.01). At the same clinical level of sedation, propofol plasma concentrations were larger when sedation was achieved by propofol alone (propofol versus propofol/remifentanil, RS 3: 2.12 mug/mL +/- 0.51 versus 1.32 +/- 0.43, P < 0.01; RS 4: 3.37 +/- 0.47 versus 1.86 +/- 0.34, P < 0.01). Our results suggest that long latency auditory evoked potentials provide an objective electrophysiological analog to the clinical assessment of sedation independent of the sedation regime used.

N100 Auditory Potential and Electroencephalogram Discriminate Propofol-induced Sedation Levels

Journal of Clinical Monitoring and Computing. Jun, 2004  |  Pubmed ID: 15562982

In the present study, we evaluated the electroencephalogram (EEG) and auditory N100 potential (N100) before and during propofol-induced sedation. The aim was to test whether using EEG and N100 the level of sedation may be evaluated.

Midlatency Auditory-evoked Potentials in the Assessment of Sedation in Cardiac Surgery Patients

Journal of Cardiothoracic and Vascular Anesthesia. Oct, 2004  |  Pubmed ID: 15578465

Midlatency auditory-evoked potentials (MLAEPs) may provide an objective measure of depth of sedation. The aim of this study was to evaluate MLAEPs for measuring sedation in cardiac surgery patients.

Blindness in the Intensive Care Unit

Anesthesia and Analgesia. Jan, 2005  |  Pubmed ID: 15616076

Blood Pressure and Vessel Recanalization in the First Hours After Ischemic Stroke

Stroke; a Journal of Cerebral Circulation. Feb, 2005  |  Pubmed ID: 15637309

Transient elevation of arterial blood pressure (BP) is frequent in acute ischemic stroke and may help to increase perfusion of tissue jeopardized by ischemia. If this is true, recanalization may eliminate the need for this BP elevation.

Estimation of Central Venous Pressure by Ultrasound

Resuscitation. Feb, 2005  |  Pubmed ID: 15680529

Increasing blood volume and cardiac output is one of the most commonly needed intervention in the primary care of traumatized and severely ill patients. Although cardiac filling pressures have severe limitations in assessing the preload, central venous pressure (CVP) is the invasive measure most frequently used in clinical practice for the assessment of volume status and cardiac preload. We combined ultrasound and tissue pressure measurement for non-invasive jugular and brachial venous pressure estimation.

Hepatosplanchnic Blood Flow Control and Oxygen Extraction Are Modified by the Underlying Mechanism of Impaired Perfusion

Critical Care Medicine. Mar, 2005  |  Pubmed ID: 15753759

To assess the effects of low hepatosplanchnic blood flow on regional blood flow control and oxygenation.

Siglec-9 Transduces Apoptotic and Nonapoptotic Death Signals into Neutrophils Depending on the Proinflammatory Cytokine Environment

Blood. Aug, 2005  |  Pubmed ID: 15827126

We report about new apoptotic and non-apoptotic death pathways in neutrophils that are initiated via the surface molecule sialic acid-binding immunoglobulin-like lectin (Siglec)-9. In normal neutrophils, Siglec-9 ligation induced apoptosis. Inflammatory neutrophils obtained from patients with acute septic shock or rheumatoid arthritis demonstrated increased Siglec-9, but normal Fas receptor-mediated cytotoxic responses when compared with normal blood neutrophils. The increased Siglec-9-mediated death was mimicked in vitro by short-term preincubation of normal neutrophils with proinflammatory cytokines, such as granulocyte/macrophage colony-stimulating factor (GM-CSF), interferon-alpha (IFN-alpha), and IFN-gamma, and was demonstrated to be caspase independent. Experiments using scavengers of reactive oxygen species (ROS) or neutrophils unable to generate ROS indicated that both Siglec-9-mediated caspase-dependent and caspase-independent forms of neutrophil death depend on ROS. Interestingly, the caspase-independent form of neutrophil death was characterized by cytoplasmic vacuolization and several other nonapoptotic morphologic features, which were also seen in neutrophils present in joint fluids from rheumatoid arthritis patients. Taken together, these data suggest that apoptotic (ROS- and caspase-dependent) and nonapoptotic (ROS-dependent) death pathways are initiated in neutrophils via Siglec-9. The new insights have important implications for the pathogenesis, diagnosis, and treatment of inflammatory diseases such as sepsis and rheumatoid arthritis.

Severe Acute Pancreatitis: Case-oriented Discussion of Interdisciplinary Management

Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]. 2005  |  Pubmed ID: 15849485

The clinical course of an episode of acute pancreatitis varies from a mild, transitory illness to a severe often necrotizing form with distant organ failure and a mortality rate of 20-40%. Patients with severe pancreatitis, representing about 15-20% of all patients with acute pancreatitis, need to be identified as early as possible after onset of symptoms allowing starting intensive care treatment early in the disease process. An episode of severe acute pancreatitis progresses in two phases. The first 10-14 days are characterized by a systemic inflammatory response syndrome maintained by the release of various inflammatory mediators. The second phase, beginning about 10-14 days after the onset of the disease is dominated by sepsis-related morbidity due to infected peripancreatic and pancreatic necrosis. This state is associated with septic multiple organ systemic failure. The importance of infection on the outcome of necrotizing pancreatitis has been clearly delineated and the pre-emptive use of broad-spectrum antibiotics that achieve effective tissue concentrations is considered standard management of patients with severe necrotizing pancreatitis, especially if associated with organ failure or extended necrosis. Patients with infected necrosis should undergo a surgical intervention. The standard open technique consisting of an organ preserving necrosectomy followed by a postoperative concept of lavage and/or drainage to evacuate necrotic debris occurring during the further course has recently been challenged by various minimally invasive approaches.

Comparison of Continuous and Intermittent Renal Replacement Therapy for Acute Renal Failure

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. Aug, 2005  |  Pubmed ID: 15886217

Mortality rates of critically ill patients with acute renal failure (ARF) requiring renal replacement therapy (RRT) are high. Intermittent and continuous RRT are available for these patients on the intensive care units (ICUs). It is unknown which technique is superior with respect to patient outcome.

Preconditioning with Monophosphoryl Lipid A Improves Survival of Critically Ischemic Tissue

Anesthesia and Analgesia. Jun, 2005  |  Pubmed ID: 15920214

In this study we sought to assess the effects of preconditioning with monophosphoryl lipid A on critically ischemic wound margins and on systemic and local hemodynamics and oxygenation during prolonged anesthesia with volatile anesthetics and narcotics. Twenty large white pigs were randomly assigned to receive either monophosphoryl lipid A 35 mug/kg IV or saline 24 h before dissection of a buttock flap. The animals were anesthetized with isoflurane (end-tidal concentration approximately 1.25%) for surgery and subsequent monitoring of hemodynamics and oxygenation both systemically and in the flap tissue for 6 h. Preconditioning resulted in increased cardiac index and oxygen delivery (both P < 0.05) and in decreased central venous pressure and systemic vascular resistance (both P < 0.01). In the preconditioned flap tissue, microcirculatory blood flow (laser Doppler flowmetry) and partial tissue oxygen tension (polarographic microprobes) were up to 2.5-fold higher compared with control (both P < 0.05) and flap necrosis was reduced by 20% on postoperative day 14 (P < 0.05). Our results suggest that preconditioning with a single dose of monophosphoryl lipid A may attenuate ischemia-related wound healing complications, which may be related to an improvement in perfusion and oxygenation of this tissue. Furthermore, preconditioning exerted a systemic cardiovascular stabilization effect during prolonged isoflurane anesthesia.

Does Fluid Loading Influence Measurements of Intestinal Permeability?

Critical Care (London, England). Jun, 2005  |  Pubmed ID: 15987395

Urinary recovery of enterally administered probes is used as a clinical test of intestinal mucosal permeability. Recently, evidence has been provided that the recovery of some but not all sugar probes is dependent on the amount of diuresis and renal function. The aim of this study was to assess the effect of fluid loading on the urinary recovery of sugar probes in healthy volunteers.

Reversible Encephalopathy Complicating Post-streptococcal Glomerulonephritis

The Pediatric Infectious Disease Journal. Jan, 2006  |  Pubmed ID: 16395114

We describe a 15-year-old boy with acute transient encephalopathy complicating poststreptococcal glomerulonephritis. Based on advanced magnetic resonance imaging, cerebral alterations were related to cerebrovascular autoregulatory dysfunction (ie, a vasogenic edema) and vasculitis was excluded. These insights into the pathophysiology improve patient management and argue against the therapeutic immunosuppression postulated by some authors.

Effects of Low Abdominal Blood Flow and Dobutamine on Blood Flow Distribution and on the Hepatic Arterial Buffer Response in Anaesthetized Pigs

Shock (Augusta, Ga.). Apr, 2006  |  Pubmed ID: 16670644

Low cardiac output impairs the hepatic arterial buffer response (HABR). Whether this is due to low abdominal blood flow per se is not known. Dobutamine is commonly used to increase cardiac output, and it may further modify hepatosplanchnic and renal vasoregulation. We assessed the effects of isolated abdominal aortic blood flow changes and dobutamine on hepatosplanchnic and renal blood flow. Twenty-five anesthetized pigs with an abdominal aorto-aortic shunt were randomized to 2 control groups [zero (n = 6) and minimal (n = 6) shunt flow], and 2 groups with 50% reduction of abdominal blood flow and either subsequent increased abdominal blood flow by shunt reduction (n = 6) or dobutamine infusion at 5 and 10 microg kg(-1) min(-1) with constant shunt flow (n = 7). Regional (ultrasound) and local (laser Doppler) intra-abdominal blood flows were measured. The HABR was assessed during acute portal vein occlusion. Sustained low abdominal blood flow, by means of shunt activation, decreased liver, gut, and kidney blood flow similarly and reduced local microcirculatory blood flow in the jejunum. Shunt flow reduction partially restored regional blood flows but not jejunal microcirculatory blood flow. Low-but not high-dose dobutamine increased gut and celiac trunk flow whereas hepatic artery and renal blood flows remained unchanged. Neither intervention altered local blood flows. The HABR was not abolished during sustained low abdominal blood flow despite substantially reduced hepatic arterial blood flow and was not modified by dobutamine. Low-but not high-dose dobutamine redistributes blood flow toward the gut and celiac trunk. The jejunal microcirculatory flow, once impaired, is difficult to restore.

Decreasing Gut Wall Glucose As an Early Marker of Impaired Intestinal Perfusion

Critical Care Medicine. Sep, 2006  |  Pubmed ID: 16878039

The aim of this study was to assess the microcirculatory and metabolic consequences of reduced mesenteric blood flow.

Effects of Prolonged Endotoxemia on Liver, Skeletal Muscle and Kidney Mitochondrial Function

Critical Care (London, England). 2006  |  Pubmed ID: 16895596

Sepsis may impair mitochondrial utilization of oxygen. Since hepatic dysfunction is a hallmark of sepsis, we hypothesized that the liver is more susceptible to mitochondrial dysfunction than the peripheral tissues, such as the skeletal muscle. We studied the effect of prolonged endotoxin infusion on liver, muscle and kidney mitochondrial respiration and on hepatosplanchnic oxygen transport and microcirculation in pigs.

Membrane Microdialysis: Evaluation of a New Method to Assess Splanchnic Tissue Metabolism

Critical Care Medicine. Oct, 2006  |  Pubmed ID: 16915109

Measuring peritoneal lactate concentrations could be useful for detecting splanchnic hypoperfusion. The aims of this study were to evaluate the properties of a new membrane-based microdialyzer in vitro and to assess the ability of the dialyzer to detect a clinically relevant decrease in splanchnic blood flow in vivo.

The Effects of Dexmedetomidine/remifentanil and Midazolam/remifentanil on Auditory-evoked Potentials and Electroencephalogram at Light-to-moderate Sedation Levels in Healthy Subjects

Anesthesia and Analgesia. Nov, 2006  |  Pubmed ID: 17056949

Avoidance of excessively deep sedation levels is problematic in intensive care patients. Electrophysiologic monitoring may offer an approach to solving this problem. Since electroencephalogram (EEG) responses to different sedation regimens vary, we assessed electrophysiologic responses to two sedative drug regimens in 10 healthy volunteers. Dexmedetomidine/remifentanil (dex/remi group) and midazolam/remifentanil (mida/remi group) were infused 7 days apart. Each combination of medications was given at stepwise intervals to reach Ramsay scores (RS) 2, 3, and 4. Resting EEG, bispectral index (BIS), and the N100 amplitudes of long-latency auditory-evoked potentials (ERP) were recorded at each level of sedation. During dex/remi, resting EEG was characterized by a recurrent high-power low-frequency pattern which became more pronounced at deeper levels of sedation. BIS Index decreased uniformly in only the dex/remi group (from 94 +/- 3 at baseline to 58 +/- 14 at RS 4) compared to the mida/remi group (from 94 +/- 2 to 76 +/- 10; P = 0.029 between groups). The ERP amplitudes decreased from 5.3 +/- 1.3 at baseline to 0.4 +/- 1.1 at RS 4 (P = 0.003) in only the mida/remi group. We conclude that ERPs in volunteers sedated with dex/remi, in contrast to mida/remi, indicate a cortical response to acoustic stimuli, even when sedation reaches deeper levels. Consequently, ERP can monitor sedation with midazolam but not with dexmedetomidine. The reverse is true for BIS.

Effect of Endotoxin, Dobutamine and Dopamine on Muscle Mitochondrial Respiration in Vitro

Journal of Endotoxin Research. 2006  |  Pubmed ID: 17254390

Mitochondrial respiration is impaired during endotoxemia. While catecholamines are frequently used in sepsis, their effects on mitochondrial function are controversial. We assessed effects of dobutamine and dopamine endotoxin on isolated muscle mitochondria.

Arterio-venous Gradients of Free Energy Change for Assessment of Systemic and Splanchnic Perfusion in Cardiac Surgery Patients

Perfusion. Nov, 2006  |  Pubmed ID: 17312859

Adequacy of organ perfusion depends on sufficient oxygen supply in relation to the metabolic needs. The aim of this study was to evaluate the relationship between gradients of free energy change, and the more commonly used parameter for the evaluation of the adequacy of organ perfusion, such as oxygen-extraction in patients undergoing valve replacement surgery using normothermic cardiopulmonary bypass (CPB).

Incidence of Low Central Venous Oxygen Saturation During Unplanned Admissions in a Multidisciplinary Intensive Care Unit: an Observational Study

Critical Care (London, England). 2007  |  Pubmed ID: 17212816

It has been shown that early central venous oxygen saturation (ScvO2)-guided optimization of hemodynamics can improve outcome in septic patients. The early ScvO2 profile of other patient groups is unknown. The aim of this study was to characterize unplanned admissions in a multidisciplinary intensive care unit (ICU) with respect to ScvO2 and outcome.

Effects of Vasopressin on Microcirculatory Blood Flow in the Gastrointestinal Tract in Anesthetized Pigs in Septic Shock

Anesthesiology. Jun, 2007  |  Pubmed ID: 17525591

Vasopressin increases arterial pressure in septic shock even when alpha-adrenergic agonists fail. The authors studied the effects of vasopressin on microcirculatory blood flow in the entire gastrointestinal tract in anesthetized pigs during early septic shock.

Intraperitoneal Microdialysis: Critique of an Editorial

Critical Care Medicine. Jul, 2007  |  Pubmed ID: 17581382

Sedation and Weaning from Mechanical Ventilation: Effects of Process Optimization Outside a Clinical Trial

Journal of Critical Care. Sep, 2007  |  Pubmed ID: 17869972

We studied the effects of reorganization and changes in the care process, including use of protocols for sedation and weaning from mechanical ventilation, on the use of sedative and analgesic drugs and on length of respiratory support and stay in the intensive care unit (ICU).

Vasopressin in Septic Shock: Effects on Pancreatic, Renal, and Hepatic Blood Flow

Critical Care (London, England). 2007  |  Pubmed ID: 18078508

Vasopressin has been shown to increase blood pressure in catecholamine-resistant septic shock. The aim of this study was to measure the effects of low-dose vasopressin on regional (hepato-splanchnic and renal) and microcirculatory (liver, pancreas, and kidney) blood flow in septic shock.

Tonometry Revisited: Perfusion-related, Metabolic, and Respiratory Components of Gastric Mucosal Acidosis in Acute Cardiorespiratory Failure

Shock (Augusta, Ga.). May, 2008  |  Pubmed ID: 18004228

Mucosal pH (pHi) is influenced by local perfusion and metabolism (mucosal-arterial pCO2 gradient, DeltapCO2), systemic metabolic acidosis (arterial bicarbonate), and respiration (arterial pCO2). We determined these components of pHi and their relation to outcome during the first 24 h of intensive care. We studied 103 patients with acute respiratory or circulatory failure (age, 63+/-2 [mean+/-SEM]; Acute Physiology and Chronic Health Evaluation II score, 20+/-1; Sequential Organ Failure Assessment score, 8+/-0). pHi, and the effects of bicarbonate and arterial and mucosal pCO2 on pHi, were assessed at admission, 6, and 24 h. pHi was reduced (at admission, 7.27+/-0.01) due to low arterial bicarbonate and increased DeltapCO2. Low pHi (<7.32) at admission (n=58; mortality, 29% vs. 13% in those with pHi>or=7.32 at admission; P=0.061) was associated with an increased DeltapCO2 in 59% of patients (mortality, 47% vs. 4% for patients with low pHi and normal DeltapCO2; P=0.0003). An increased versus normal DeltapCO2, regardless of pHi, was associated with increased mortality at admission (51% vs. 5%; P<0.0001; n=39) and at 6 h (34% vs. 13%; P=0.016; n=45). A delayed normalization or persistently low pHi (n=47) or high DeltapCO2 (n=25) was associated with high mortality (low pHi [34%] vs. high DeltapCO2 [60%]; P=0.046). In nonsurvivors, hypocapnia increased pHi at baseline, 6, and 24 h (all P

Prevention of Delayed Cerebral Vasospasm by Continuous Intrathecal Infusion of Glyceroltrinitrate and Nimodipine in the Rabbit Model in Vivo

Intensive Care Medicine. May, 2008  |  Pubmed ID: 18214428

Intrathecal bolus administration of nitric oxide donors and calcium channel antagonists has been proposed to reduce cerebral vasospasm (CVS) in animal subarachnoid hemorrhage (SAH) models. Intrathecal continuous administration of these substances for CVS prevention has not been extensively evaluated. This study compared the efficacy of continuous intrathecal infusions of the NO donor glyceroltrinitrate and nimodipine in preventing delayed CVS associated with SAH in an animal model in vivo.

The Immediate and Sustained Effects of Volume Challenge on Regional Blood Flows in Pigs

Anesthesia and Analgesia. Feb, 2008  |  Pubmed ID: 18227321

The postoperative assessment of volume status is not straightforward because of concomitant changes in intravascular volume and vascular tone. Hypovolemia and blood flow redistribution may compromise the perfusion of the intraabdominal organs. We investigated the effects of a volume challenge in different intra- and extraabdominal vascular beds.

Development and Simultaneous Application of Multiple Care Protocols in Critical Care: a Multicenter Feasibility Study

Intensive Care Medicine. Aug, 2008  |  Pubmed ID: 18385977

To test the feasibility of and interactions among three software-driven critical care protocols.

Orthogonal Polarization Spectroscopy to Detect Mesenteric Hypoperfusion

Intensive Care Medicine. Oct, 2008  |  Pubmed ID: 18516589

Orthogonal polarization spectral (OPS) imaging is used to assess mucosal microcirculation. We tested sensitivity and variability of OPS in the assessment of mesenteric blood flow (Qsma) reduction.

Thermodilution and Esophageal Doppler Ultrasound in the Assessment of Blood Flow Changes Induced by Endotoxin and Dobutamine

The Journal of Trauma. Jul, 2008  |  Pubmed ID: 18580513

Intermittent (IT) and continuous (CT) thermodilution and esophageal Doppler (ED), are all used for hemodynamic monitoring. The aim of this study was to test the agreement between these methods during endotoxin (ET) and dobutamine infusion.

Norepinephrine to Increase Blood Pressure in Endotoxaemic Pigs is Associated with Improved Hepatic Mitochondrial Respiration

Critical Care (London, England). 2008  |  Pubmed ID: 18625036

Low 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.

Entropy and Bispectral Index for Assessment of Sedation, Analgesia and the Effects of Unpleasant Stimuli in Critically Ill Patients: an Observational Study

Critical Care (London, England). 2008  |  Pubmed ID: 18796156

Sedative and analgesic drugs are frequently used in critically ill patients. Their overuse may prolong mechanical ventilation and length of stay in the intensive care unit. Guidelines recommend use of sedation protocols that include sedation scores and trials of sedation cessation to minimize drug use. We evaluated processed electroencephalography (response and state entropy and bispectral index) as an adjunct to monitoring effects of commonly used sedative and analgesic drugs and intratracheal suctioning.

Dexmedetomidine Versus Propofol/midazolam for Long-term Sedation During Mechanical Ventilation

Intensive Care Medicine. Feb, 2009  |  Pubmed ID: 18795253

To compare dexmedetomidine (DEX) with standard care (SC, either propofol or midazolam) for long-term sedation in terms of maintaining target sedation and length of intensive care unit (ICU) stay.

Inverse Thermodilution with Conventional Pulmonary Artery Catheters for the Assessment of Cerebral, Hepatic, Renal, and Femoral Blood Flow

Shock (Augusta, Ga.). Aug, 2009  |  Pubmed ID: 19033887

Assessment of regional blood flow changes is difficult in the clinical setting. We tested whether conventional pulmonary artery catheters (PACs) can be used to measure regional venous blood flows by inverse thermodilution (ITD). Inverse thermodilution was tested in vitro and in vivo using perivascular ultrasound Doppler (USD) flow probes as a reference. In anesthetized pigs, PACs were inserted in jugular, hepatic, renal, and femoral veins, and their measurements were compared with simultaneous USD flow measurements from carotid, hepatic, renal, and femoral arteries and from portal vein. Fluid boluses were injected through the PAC's distal port, and temperature changes were recorded from the proximally located thermistor. Injectates of 2 and 5 mL at 22 degrees C and 4 degrees C were used. Flows were altered by using a roller pump (in vitro), and infusion of dobutamine and induction of cardiac tamponade, respectively. In vitro: At blood flows between 400 mL . min-1 and 700 mL . min-1 (n = 50), ITD and USD correlated well (r = 0.86, P < 0.0001), with bias and limits of agreement of 3 +/- 101 mL . min-1. In vivo: 514 pairs of measurements had to be excluded from analysis for technical reasons, and 976 were analyzed. Best correlations were r = 0.87 (P < 0.0001) for renal flow and r = 0.46 (P < 0.0001) for hepatic flow. No significant correlation was found for cerebral and femoral flows. Inverse thermodilution using conventional PAC compared moderately well with USD for renal but not for other flows despite good in vitro correlation in various conditions. In addition, this method has significant technical limitations.

Increased Splanchnic Oxygen Extraction Because of Routine Nursing Procedures

Critical Care Medicine. Feb, 2009  |  Pubmed ID: 19114883

Multiple organ failure is a common complication of acute circulatory and respiratory failure. We hypothesized that therapeutic interventions used routinely in intensive care can interfere with the perfusion of the gut and the liver, and thereby increase the risk of mismatch between oxygen supply and demand.

Shedding Light on Microcirculation?

Intensive Care Medicine. Mar, 2009  |  Pubmed ID: 19125231

Arterial Blood Pressure During Early Sepsis and Outcome

Intensive Care Medicine. Jul, 2009  |  Pubmed ID: 19189077

To evaluate the association between arterial blood pressure (ABP) during the first 24 h and mortality in sepsis.

Intra- and Inter-individual Variation of BIS-index and Entropy During Controlled Sedation with Midazolam/remifentanil and Dexmedetomidine/remifentanil in Healthy Volunteers: an Interventional Study

Critical Care (London, England). 2009  |  Pubmed ID: 19228415

We studied intra-individual and inter-individual variability of two online sedation monitors, BIS and Entropy, in volunteers under sedation.

Assessment of Splanchnic Blood Flow Using Magnetic Resonance Imaging

European Journal of Gastroenterology & Hepatology. Jun, 2009  |  Pubmed ID: 19293721

The splanchnic circulation has an important function in the body under both physiological and pathophysiological conditions. Despite its importance, no reliable noninvasive procedures for estimating splanchnic circulation have been established. The aim of this study was to evaluate MRI as a tool for assessing intra-abdominal blood flows of the aorta, portal vein (VPO) and the major intestinal and hepatic vessels.

Different Patterns of Siglec-9-mediated Neutrophil Death Responses in Septic Shock

Shock (Augusta, Ga.). Oct, 2009  |  Pubmed ID: 19295491

Sialic-acid-binding immunoglobulin-like lectin (Siglec) 9 mediates death signals in neutrophils. The objective of this study was to determine the heterogeneity of neutrophil death responses in septic shock patients and to analyze whether these ex vivo data are related to the severity and outcome of septic shock. In this prospective cohort study, blood samples of patients with septic shock (n = 26) in a medical-surgical intensive care unit (ICU) were taken within 24 h of starting the treatment of septic shock (phase A), after circulatory stabilization (phase B), and 10 days after admission or at ICU discharge if earlier (phase C). Neutrophil death was quantified in the presence and absence of an agonistic anti-Siglec-9 antibody after 24 h ex vivo. In phase A, two distinct patterns of Siglec-9-mediated neutrophil death were observed: resistance to neutrophil death (n = 14; Siglec-9 nonresponders) and increased neutrophil death (n = 12; Siglec-9 responders) after Siglec-9 ligation compared with neutrophils from normal donors. Experiments using a pharmacological pan-caspase-inhibitor provided evidence for caspase-independent neutrophil death in Siglec-9 responders upon Siglec-9 ligation. There were no differences between Siglec-9 responders and nonresponders in length of ICU or hospital stay of survivors or severity of organ dysfunction. Taken together, septic shock patients exhibit different ex vivo death responses of blood neutrophils after Siglec-9 ligation early in shock. Both the resistance and the increased susceptibility to Siglec-9-mediated neutrophil death tend to normalize within 72 h after shock. Further studies are required to understand the role of Siglec-9-mediated neutrophil death in septic shock.

Thromboelastometry for the Assessment of Coagulation Abnormalities in Early and Established Adult Sepsis: a Prospective Cohort Study

Critical Care (London, England). 2009  |  Pubmed ID: 19331653

The inflammatory response to an invading pathogen in sepsis leads to complex alterations in hemostasis by dysregulation of procoagulant and anticoagulant factors. Recent treatment options to correct these abnormalities in patients with sepsis and organ dysfunction have yielded conflicting results. Using thromboelastometry (ROTEM(R)), we assessed the course of hemostatic alterations in patients with sepsis and related these alterations to the severity of organ dysfunction.

Norepinephrine-induced Hypertension Dilates Vasospastic Basilar Artery After Subarachnoid Haemorrhage in Rabbits

Acta Neurochirurgica. May, 2009  |  Pubmed ID: 19343267

Vasopressor-induced hypertension is routinely indicated for prevention and treatment of cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH). Mechanisms underlying patients' clinical improvement during vasopressor-induced hypertension remain incompletely understood. The aim of this study was to evaluate angiographic effects of normovolaemic Norepinephrine (NE)-induced hypertension therapy on the rabbit basilar artery (BA) after SAH.

Elevated Level of Endothelin-1 in Cerebrospinal Fluid and Lack of Nitric Oxide in Basilar Arterial Plasma Associated with Cerebral Vasospasm After Subarachnoid Haemorrhage in Rabbits

Acta Neurochirurgica. Jul, 2009  |  Pubmed ID: 19415172

The role of endothelin-1 (ET-1) and nitric oxide (NO) as two important mediators in the development of cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH) is controversial. The objective of this study was to determine whether local levels of ET-1 and NO in cerebral arterial plasma and/or in cerebrospinal fluid (CSF) are associated with the occurrence of CVS after SAH.

Physical and Occupational Therapy During Sedation Stops

Lancet. May, 2009  |  Pubmed ID: 19446327

Evaluation of Physical and Mental Recovery Status After Elective Liver Resection

European Journal of Anaesthesiology. Jul, 2009  |  Pubmed ID: 19509504

This prospective, clinical pilot trial compared the Short Form 36 Health Survey (SF-36) and a nine-item quality of recovery [Quality of Recovery 9 (QoR-9)] survey to assess the 1-week outcome after liver resection and prediction of postoperative complications from baseline values before liver resection.

Septic Shock Resuscitation: What Goals and How to Achieve Them?

Critical Care (London, England). 2009  |  Pubmed ID: 19519939

The need to achieve adequate tissue oxygen delivery early in patients with septic shock is well established. However, it is less well recognized that tissue hypoperfusion can exist despite normalization of systemic hemodynamics. Efforts to resuscitate septic patients until adequate tissue perfusion has been achieved can potentially improve outcome. In a multicenter study, 130 patients with septic shock were resuscitated within 12 hours of diagnosis using a protocol including goals for mean arterial and pulmonary artery occluded pressures, urinary output, arterial pH, and hemoglobin goals. They were then randomly assigned to further resuscitation with either a cardiac index (>or= 3 l/minute per m2) or a gastric mucosal pH (>or= 7.32) target. The intensive care unit length of stay and 28-day mortality did not differ between groups, but more patients in the cardiac index group were in the target range, both at baseline and after resuscitation, as compared with the gastric mucosal pH group. In contrast to cardiac index, gastric mucosal pH at baseline and at 24 and 48 hours predicted mortality. Whether other targets for the chosen variables, or different and--in particular--earlier resuscitation efforts would have favored one group cannot be concluded from the data provided.

Peri-operative Adrenocortical Response to Low-dose (1 Microg) ACTH and Relation to Postoperative Complications in Patients Undergoing Elective Abdominal Surgery

Surgery. Jul, 2009  |  Pubmed ID: 19541014

To test the hypothesis that reduced responsiveness to adrenocorticotropin (ACTH) stimulation before elective major abdominal surgery is associated with an increased incidence of postoperative complications.

Effects of Endotoxin and Catecholamines on Hepatic Mitochondrial Respiration

Inflammation. Oct, 2009  |  Pubmed ID: 19603262

Catecholamines are frequently used in sepsis, but their interaction with mitochondrial function is controversial. We incubated isolated native and endotoxin-exposed swine liver mitochondria with either dopamine, dobutamine, noradrenaline or placebo for 1 h. Mitochondrial State 3 and 4 respiration and their ratio (RCR) were determined for respiratory chain complexes I, II and IV. All catecholamines impaired glutamate-dependent RCR (p = 0.046), predominantly in native mitochondria. Endotoxin incubation alone induced a decrease in glutamate-dependent RCR compared to control samples (p = 0.002). We conclude that catecholamines and endotoxin impair the efficiency of mitochondrial complex I respiration in vitro.

Treatment of Acute Renal Failure in the Intensive Care Unit: Lower Costs by Intermittent Dialysis Than Continuous Venovenous Hemodiafiltration

Artificial Organs. Aug, 2009  |  Pubmed ID: 19624581

Intermittent and continuous renal replacement therapies (RRTs) are available for the treatment of acute renal failure (ARF) in the intensive care unit (ICU). Although at present there are no adequately powered survival studies, available data suggest that both methods are equal with respect to patient outcome. Therefore, cost comparison between techniques is important for selecting the modality. Expenditures were prospectively assessed as a secondary end point during a controlled, randomized trial comparing intermittent hemodialysis (IHD) with continuous venovenous hemodiafiltration (CVVHDF). The outcome of the primary end points of this trial, that is, ICU and in-hospital mortality, has been previously published. One hundred twenty-five patients from a Swiss university hospital ICU were randomized either to CVVHDF or IHD. Out of these, 42 (CVVHDF) and 34 (IHD) were available for cost analysis. Patients' characteristics, delivered dialysis dose, duration of stay in the ICU or hospital, mortality rates, and recovery of renal function were not different between the two groups. Detailed 24-h time and material consumption protocols were available for 369 (CVVHDF) and 195 (IHD) treatment days. The mean daily duration of CVVHDF was 19.5 +/- 3.2 h/day, resulting in total expenditures of Euro 436 +/- 21 (21% for human resources and 79% for technical devices). For IHD (mean 3.0 +/- 0.4 h/treatment), the costs were lower (Euro 268 +/- 26), with a larger proportion for human resources (45%). Nursing time spent for CVVHDF was 113 +/- 50 min, and 198 +/- 63 min per IHD treatment. Total costs for RRT in ICU patients with ARF were lower when treated with IHD than with CVVHDF, and have to be taken into account for the selection of the method of RRT in ARF on the ICU.

Auditory Event-related Potentials, Bispectral Index, and Entropy for the Discrimination of Different Levels of Sedation in Intensive Care Unit Patients

Anesthesia and Analgesia. Sep, 2009  |  Pubmed ID: 19690250

Sedation protocols, including the use of sedation scales and regular sedation stops, help to reduce the length of mechanical ventilation and intensive care unit stay. Because clinical assessment of depth of sedation is labor-intensive, performed only intermittently, and interferes with sedation and sleep, processed electrophysiological signals from the brain have gained interest as surrogates. We hypothesized that auditory event-related potentials (ERPs), Bispectral Index (BIS), and Entropy can discriminate among clinically relevant sedation levels.

Hypoxia Inducible Factor-1 Alpha Induction by Tumour Necrosis Factor-alpha, but Not by Toll-like Receptor Agonists, Modulates Cellular Respiration in Cultured Human Hepatocytes

Liver International : Official Journal of the International Association for the Study of the Liver. Nov, 2009  |  Pubmed ID: 19744167

Genes encoding for some of the mitochondrial proteins are under the control of the transcriptional factor hypoxia inducible factor-1 alpha (HIF-1 alpha), which can accumulate under normoxic conditions in inflammatory states. The aim of this study was to evaluate the effects of cobalt chloride (CoCl(2), a hypoxia mimicking agent), tumour necrosis factor-alpha (TNF-alpha) and toll-like receptor (TLR) -2, -3 and -4 agonists on HIF-1 alpha accumulation, and further on HIF-1 alpha-mediated modulation of mitochondrial respiration in cultured human hepatocytes.

Hemodynamic Variables and Mortality in Cardiogenic Shock: a Retrospective Cohort Study

Critical Care (London, England). 2009  |  Pubmed ID: 19799772

Despite the key role of hemodynamic goals, there are few data addressing the question as to which hemodynamic variables are associated with outcome or should be targeted in cardiogenic shock patients. The aim of this study was to investigate the association between hemodynamic variables and cardiogenic shock mortality.

Effect of Fluid Resuscitation on Mortality and Organ Function in Experimental Sepsis Models

Critical Care (London, England). 2009  |  Pubmed ID: 19930656

Several recent studies have shown that a positive fluid balance in critical illness is associated with worse outcome. We tested the effects of moderate vs. high-volume resuscitation strategies on mortality, systemic and regional blood flows, mitochondrial respiration, and organ function in two experimental sepsis models.

Usefulness of a Clinical Diagnosis of ICU-acquired Paresis to Predict Outcome in Patients with SIRS and Acute Respiratory Failure

Intensive Care Medicine. Jan, 2010  |  Pubmed ID: 19760204

Neuromuscular abnormalities are common in ICU patients. We aimed to assess the incidence of clinically diagnosed ICU-acquired paresis (ICUAP) and its impact on outcome.

Perioperative Metabolic Changes in Patients Undergoing Cardiac Surgery

Nutrition (Burbank, Los Angeles County, Calif.). Apr, 2010  |  Pubmed ID: 20053534

Perioperative metabolic changes in cardiac surgical patients are not only induced by tissue injury and extracorporeal circulation per se: the systemic inflammatory response to surgical trauma and extracorporeal circulation, perioperative hypothermia, cardiovascular and neuroendocrine responses, and drugs and blood products used to maintain cardiovascular function and anesthesia contribute to varying degrees. The pathophysiologic changes include increased oxygen consumption and energy expenditure; increased secretion of adrenocorticotrophic hormone, cortisol, epinephrine, norepinephrine, insulin, and growth hormone; and decreased total tri-iodothyronine levels. Easily measurable metabolic consequences of these changes include hyperglycemia, hyperlactatemia, increased aspartate, glutamate and free fatty acid concentrations, hypokalemia, increased production of inflammatory cytokines, and increased consumption of complement and adhesion molecules. Nutritional risk before elective cardiac surgery-defined as preoperative unintended pathologic weight loss/low amount of food intake in the preceding week or low body mass index-is related to adverse postoperative outcome. Improvements in surgical techniques, anesthesia, and perioperative management have been designed to minimize the stressful stimulus to catabolism, thereby slowing the wasting process to the point where much less nutrition is required to meet metabolic requirements. Early nutrition in cardiac surgery is safe and well tolerated.

The Effects of Mechanical Ventilation on Hepato-splanchnic Perfusion

Current Opinion in Critical Care. Apr, 2010  |  Pubmed ID: 20134320

Mechanical ventilation is a cornerstone of ICU treatment. Because of its interaction with blood flow and intra-abdominal pressure, mechanical ventilation has the potential to alter hepato-splanchnic perfusion, abdominal organ function and thereby outcome of the most critically ill patients.

Effects of Lung Recruitment Maneuvers on Splanchnic Organ Perfusion During Endotoxin-induced Pulmonary Arterial Hypertension

Shock (Augusta, Ga.). Nov, 2010  |  Pubmed ID: 20357696

Lung recruitment maneuvers (RMs), used to reopen atelectatic lung units and to improve oxygenation during mechanical ventilation, may result in hemodynamic impairment. We hypothesize that pulmonary arterial hypertension aggravates the consequences of RMs in the splanchnic circulation. Twelve anesthetized pigs underwent laparotomy and prolonged postoperative ventilation. Systemic, regional, and organ blood flows were monitored. After 6 h (= baseline), a recruitment maneuver was performed with sustained inflation of the lungs. Thereafter, the pigs were randomly assigned to group C (control, n = 6) or group E with endotoxin-induced pulmonary arterial hypertension (n = 6). Endotoxemia resulted in a normotensive and hyperdynamic state and a deterioration of the oxygenation index by 33%. The RM was then repeated in both groups. Pulmonary artery pressure increased during lipopolysaccharide infusion from 17 ± 2 mmHg (mean ± SD) to 31 ± 10 mmHg and remained unchanged in controls (P < 0.05). During endotoxemia, RM decreased aortic pulse pressure from 37 ± 14 mmHg to 27 ± 13 mmHg (mean ± SD, P = 0.024). The blood flows of the renal artery, hepatic artery, celiac trunk, superior mesenteric artery, and portal vein decreased to 71% ± 21%, 69% ± 20%, 76% ± 16%, 79% ± 18%, and 81% ± 12%, respectively, of baseline flows before RM (P < 0.05 all). Organ perfusion of kidney cortex, kidney medulla, liver, and jejunal mucosa in group E decreased to 65% ± 19%, 77% ± 13%, 66% ± 26%, and 71% ± 12%, respectively, of baseline flows (P < 0.05 all). The corresponding recovery to at least 90% of baseline regional blood flow and organ perfusion lasted 1 to 5 min. Importantly, the decreases in regional blood flows and organ perfusion and the time to recovery of these flows did not differ from the controls. In conclusion, lipopolysaccharide-induced pulmonary arterial hypertension does not aggravate the RM-induced significant but short-lasting decreases in systemic, regional, and organ blood flows.

Splanchnic Vasoregulation After Major Abdominal Surgery in Pigs

World Journal of Surgery. Sep, 2010  |  Pubmed ID: 20383500

Unrecognized reduction of blood supply to intestinal organs is associated with significant postoperative morbidity in abdominal surgery. The aim of this study was to determine whether--in the absence of hypovolemia--intestinal hypoperfusion as a result of blood flow redistribution occurs after abdominal surgery.

Physiologic Response to Changing Positive End-expiratory Pressure During Neurally Adjusted Ventilatory Assist in Sedated, Critically Ill Adults

Chest. Sep, 2010  |  Pubmed ID: 20435654

Neurally adjusted ventilatory assist (NAVA) delivers airway pressure (Paw) in proportion to neural inspiratory drive as reflected by electrical activity of the diaphragm (EAdi). Changing positive end-expiratory pressure (PEEP) impacts respiratory muscle load and function and, hence, EAdi. We aimed to evaluate how PEEP affects the breathing pattern and neuroventilatory efficiency during NAVA.

500 Ml of Blood Loss Does Not Decrease Non-invasive Tissue Oxygen Saturation (StO2) As Measured by Near Infrared Spectroscopy - A Hypothesis Generating Pilot Study in Healthy Adult Women

Journal of Trauma Management & Outcomes. 2010  |  Pubmed ID: 20465822

The goal when resuscitating trauma patients is to achieve adequate tissue perfusion. One parameter of tissue perfusion is tissue oxygen saturation (StO2), as measured by near infrared spectroscopy. Using a commercially available device, we investigated whether clinically relevant blood loss of 500 ml in healthy volunteers can be detected by changes in StO2 after a standardized ischemic event.

Effects of TLR Agonists on the Hypoxia-regulated Transcription Factor HIF-1alpha and Dendritic Cell Maturation Under Normoxic Conditions

PloS One. 2010  |  Pubmed ID: 20539755

Dendritic cells (DC) are professional antigen presenting cells that represent an important link between innate and adaptive immunity. Danger signals such as toll-like receptor (TLR) agonists induce maturation of DC leading to a T-cell mediated adaptive immune response. In this study, we show that exogenous as well as endogenous inflammatory stimuli for TLR4 and TLR2 induce the expression of HIF-1alpha in human monocyte-derived DC under normoxic conditions. On the functional level, inhibition of HIF-1alpha using chetomin (CTM), YC-1 and digoxin lead to no consistent effect on MoDC maturation, or cytokine secretion despite having the common effect of blocking HIF-1alpha stabilization or activity through different mechanisms. Stabilization of HIF-1alpha protein by hypoxia or CoCl(2) did not result in maturation of human DC. In addition, we could show that TLR stimulation resulted in an increase of HIF-1alpha controlled VEGF secretion. These results show that stimulation of human MoDC with exogenous as well as endogenous TLR agonists induces the expression of HIF-1alpha in a time-dependent manner. Hypoxia alone does not induce maturation of DC, but is able to augment maturation after TLR ligation. Current evidence suggests that different target genes may be affected by HIF-1alpha under normoxic conditions with physiological roles that differ from those induced by hypoxia.

Pulse-pressure Variation and Hemodynamic Response in Patients with Elevated Pulmonary Artery Pressure: a Clinical Study

Critical Care (London, England). 2010  |  Pubmed ID: 20540730

Pulse-pressure variation (PPV) due to increased right ventricular afterload and dysfunction may misleadingly suggest volume responsiveness. We aimed to assess prediction of volume responsiveness with PPV in patients with increased pulmonary artery pressure.

Pulse Pressure Variation and Volume Responsiveness During Acutely Increased Pulmonary Artery Pressure: an Experimental Study

Critical Care (London, England). 2010  |  Pubmed ID: 20576099

We found that pulse pressure variation (PPV) did not predict volume responsiveness in patients with increased pulmonary artery pressure. This study tests the hypothesis that PPV does not predict fluid responsiveness during an endotoxin-induced acute increase in pulmonary artery pressure and right ventricular loading.

Increasing Abdominal Pressure with and Without PEEP: Effects on Intra-peritoneal, Intra-organ and Intra-vascular Pressures

BMC Gastroenterology. 2010  |  Pubmed ID: 20598159

Intra-organ and intra-vascular pressures can be used to estimate intra-abdominal pressure. The aim of this prospective, interventional study was to assess the effect of PEEP on the accuracy of pressure estimation at different measurement sites in a model of increased abdominal pressure.

Extra-intracranial Blood Shunt Mimicking Aneurysm Rupture: Intracranial-pressure-controlled Rabbit Subarachnoid Hemorrhage Model

Journal of Neuroscience Methods. Aug, 2010  |  Pubmed ID: 20624427

The achieved degree of delayed cerebral vasospasm (DCVS) in the rabbits most frequently applied cistern magna blood injection model is often mild. The aim of this study was to characterize and evaluate the feasibility of an experimental SAH technique that mimics pathophysiological mechanisms and triggers higher degrees of DCVS.

Brain Herniation in a Patient with Apparently Normal Intracranial Pressure: a Case Report

Journal of Medical Case Reports. 2010  |  Pubmed ID: 20807427

Intracranial pressure monitoring is commonly implemented in patients with neurologic injury and at high risk of developing intracranial hypertension, to detect changes in intracranial pressure in a timely manner. This enables early and potentially life-saving treatment of intracranial hypertension.

Does Hypercapnic Acidosis Preserve Mucosal Oxygenation During Hemorrhage?

Shock (Augusta, Ga.). Dec, 2010  |  Pubmed ID: 21079493

Toll-like Receptor-3-induced Mitochondrial Dysfunction in Cultured Human Hepatocytes

Mitochondrion. Jan, 2011  |  Pubmed ID: 20691286

Several studies have shown the presence of liver mitochondrial dysfunction during sepsis. TLR3 recognizes viral double-stranded RNA and host endogenous cellular mRNA released from damaged cells. TLR3 ligand amplifies the systemic hyperinflammatory response observed during sepsis and in sepsis RNA escaping from damaged tissues/cells may serve as an endogenous ligand for TLR3 thereby modulating immune responses. This study addressed the hypothesis that TLR3 might regulate mitochondrial function in cultured human hepatocytes. HepG2 cells were exposed to TLR-3 ligand (dsRNA--polyinosine-polycytidylic acid; Poly I:C) and mitochondrial respiration was measured. Poly I:C induced a reduction in maximal mitochondrial respiration of human hepatocytes which was prevented partially by preincubation with cyclosporine A (a mitochondrial permeability transition pore-opening inhibitor). Poly-I:C induced activation of NF-κB, and the mitochondrial dysfunction was accompanied by caspase-8 but not caspase-3 activation and by no major alterations in cellular or mitochondrial ultrastructure.

Review Article: Improving Outcome After Major Surgery: Pathophysiological Considerations

Anesthesia and Analgesia. May, 2011  |  Pubmed ID: 20736438

Surgical and anesthesia-related techniques may reduce physical stress for patients undergoing high-risk surgery, but major surgery is increasingly performed in patients with substantial comorbidities. Strategies for improving the outcome for such patients include approaches that both increase tissue oxygen delivery and reduce metabolic demand. However, these strategies have produced conflicting results. To understand the success and failure of attempts to improve postoperative outcome, the pathophysiology of perioperative hemodynamic, metabolic, and immunological alterations should be analyzed. Our aim in this review is to provide a survey of fields of opportunities for improving outcome after major surgery. The issues are approached from 3 different angles: the view of the patient, the view of the surgical intervention, and the view of the anesthesia. Special attention is also given to what could be considered the result of the interaction among the 3: perioperative inflammation and immune response.

Current Approach to the Haemodynamic Management of Septic Shock Patients in European Intensive Care Units: a Cross-sectional, Self-reported Questionnaire-based Survey

European Journal of Anaesthesiology. Apr, 2011  |  Pubmed ID: 21088597

The aim of this survey was to investigate clinicians' current approach to the haemodynamic management and resuscitation endpoints in septic shock.

Comparison of Non-calibrated Pulse-contour Analysis with Continuous Thermodilution for Cardiac Output Assessment in Patients with Induced Hypothermia After Cardiac Arrest

Resuscitation. Apr, 2011  |  Pubmed ID: 21292380

Induced mild hypothermia after cardiac arrest interferes with clinical assessment of the cardiovascular status of patients. In this situation, non-invasive cardiac output measurement could be useful. Unfortunately, arterial pulse contour is altered by temperature, and the performance of devices using arterial blood pressure contour analysis to derive cardiac output may be insufficient.

Comparison of Porcine and Human Coagulation by Thrombelastometry

Thrombosis Research. Nov, 2011  |  Pubmed ID: 21492909

Although the pig is a standard model for the evaluation of various diseases in humans, including coagulopathy, it is not clear whether results in animals can be extrapolated to man.

Continuous Intrathecal Glyceryl Trinitrate Prevents Delayed Cerebral Vasospasm in the Single-SAH Rabbit Model in Vivo

Acta Neurochirurgica. Aug, 2011  |  Pubmed ID: 21671141

Delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is a major cause of high morbidity and mortality. The reduced availability of nitric oxide (NO) in blood and cerebrospinal fluid (CSF) is well established as a key mechanism of vasospasm. Systemic administration of glyceryl trinitrate (GTN), an NO donor also known as nitroglycerin, has failed to be established in clinical settings to prevent vasospasm because of its adverse effects, particularly hypotension. The purpose of this study was to analyze the effect of intrathecally administered GTN on vasospasm after experimental SAH in the rabbit basilar artery.

Early Non-invasive Cardiac Output Monitoring in Hemodynamically Unstable Intensive Care Patients: a Multi-center Randomized Controlled Trial

Critical Care (London, England). 2011  |  Pubmed ID: 21676229

Acute hemodynamic instability increases morbidity and mortality. We investigated whether early non-invasive cardiac output monitoring enhances hemodynamic stabilization and improves outcome.

Dimethyloxalylglycine Stabilizes HIF-1α in Cultured Human Endothelial Cells and Increases Random-pattern Skin Flap Survival in Vivo

Plastic and Reconstructive Surgery. Aug, 2011  |  Pubmed ID: 21788833

The goal of this study was to evaluate in vitro and in vivo the effects of up-regulation of the proangiogenic hypoxia inducible factor (HIF)-1α induced by dimethyloxalylglycine on endothelial cell cultures and on skin flap survival.

CO(2)-Dependent Vasomotor Reactivity of Cerebral Arteries in Patients with Severe Traumatic Brain Injury: Time Course and Effect of Augmentation of Cardiac Output with Dobutamine

Journal of Neurotrauma. Jun, 2012  |  Pubmed ID: 21501044

Failing cerebral blood flow (CBF) autoregulation may contribute to cerebral damage after traumatic brain injury (TBI). The purpose of this study was to describe the time course of CO(2)-dependent vasoreactivity, measured as CBF velocity in response to hyperventilation (vasomotor reactivity [VMR] index). We included 13 patients who had had severe TBI, 8 of whom received norepinephrine (NE) based on clinical indication. In these patients, measurements were also performed after dobutamine administration, with a goal of increasing cardiac output by 30%. Blood flow velocity was measured with transcranial Doppler ultrasound in both hemispheres. All patients except one had an abnormal VMR index in at least one hemisphere within the first 24 h after TBI. In those patients who did not receive catecholamines, mean VMR index recovered within the first 48 to 72 h. In contrast, in patients who received NE within the first 48 h period, VMR index did not recover on the second day. Cardiac output and mean CBF velocity increased significantly during dobutamine administration, but VMR index did not change significantly. In conclusion, CO(2) vasomotor reactivity was abnormal in the first 24 h after TBI in most of the patients, but recovered within 48 h in those patients who did not receive NE, in contrast to those eventually receiving the drug. Addition of dobutamine to NE had variable but overall insignificant effects on CO(2) vasomotor reactivity.

Effects of Catecholamines on Hepatic and Skeletal Muscle Mitochondrial Respiration After Prolonged Exposure to Faecal Peritonitis in Pigs

Innate Immunity. Apr, 2012  |  Pubmed ID: 21525237

Use of norepinephrine to increase blood pressure in septic animals has been associated with increased efficiency of hepatic mitochondrial respiration. The aim of this study was to evaluate whether the same effect could be reproduced in isolated hepatic mitochondria after prolonged in vivo exposure to faecal peritonitis. Eighteen pigs were randomized to 27 h of faecal peritonitis and to a control condition (n = 9 each group). At the end, hepatic mitochondria were isolated and incubated for one hour with either norepinephrine or placebo, with and without pretreatment with the specific receptor antagonists prazosin and yohimbine. Mitochondrial state 3 and state 4 respiration were measured for respiratory chain complexes I and II, and state 3 for complex IV using high-resolution respirometry, and respiratory control ratios were calculated. Additionally, skeletal muscle mitochondrial respiration was evaluated after incubation with norepinephrine and dobutamine with and without the respective antagonists (atenolol, propranolol and phentolamine for dobutamine). Faecal peritonitis was characterized by decreasing blood pressure and stroke volume, and maintained systemic oxygen consumption. Neither faecal peritonitis nor any of the drugs or drug combinations had measurable effects on hepatic or skeletal muscle mitochondrial respiration. Norepinephrine did not improve the efficiency of complex I- and complex II-dependent isolated hepatic mitochondrial respiration [respiratory control ratio (RCR) complex I: 5.6 ± 5.3 (placebo) vs. 5.4 ± 4.6 (norepinephrine) in controls and 2.7 ± 2.1 (placebo) vs. 2.9 ± 1.5 (norepinephrine) in septic animals; RCR complex II: 3.5 ± 2.0 (placebo) vs. 3.5 ± 1.8 (norepinephrine) in controls; 2.3 ± 1.6 (placebo) vs. 2.2 ± 1.1 (norepinephrine) in septic animals]. Prolonged faecal peritonitis did not affect either hepatic or skeletal muscle mitochondrial respiration. Subsequent incubation of isolated mitochondria with norepinephrine and dobutamine did not significantly influence their respiration.

Traumatic Subarachnoid Hemorrhage, Basal Ganglia Hematoma and Ischemic Stroke Caused by a Torn Lenticulostriate Artery

Acta Neurochirurgica. Jan, 2012  |  Pubmed ID: 21976234

Subarachnoid hemorrhage (SAH), basal ganglia hematoma (BGH) and ischemic stroke are common diseases with diverging therapies. The simultaneous occurrence of these diseases is rare and complicates the therapy. We report the case of a 30-year-old man with a ruptured lenticulostriate artery after traumatic brain injury that caused the combination of SAH, BGH and ischemic stroke and subsequent cerebral vasospasm. This rupture mimicked the pathophysiology and imaging appearance of aneurysmal SAH. The site of rupture was not secured by any treatment; however, hyperdynamic therapy and percutaneous transluminal angioplasty were feasible in this setting to prevent additional delayed neurological deficit.

Postoperative Splanchnic Blood Flow Redistribution in Response to Fluid Challenges in the Presence and Absence of Endotoxemia in a Porcine Model

Shock (Augusta, Ga.). Jan, 2012  |  Pubmed ID: 21993445

We hypothesized that fluid administration may increase regional splanchnic perfusion after abdominal surgery-even in the absence of a cardiac stroke volume (SV) increase and independent of accompanying endotoxemia. Sixteen anesthetized pigs underwent abdominal surgery with flow probe fitting around splanchnic vessels and carotid arteries. They were randomized to continuous placebo or endotoxin infusion, and when clinical signs of hypovolemia (mean arterial pressure, <60 mmHg; heart rate, >100 beats · min(-1); urine production, <0.5 mL · kg(-1) · h(-1); arterial lactate concentration, >2 mmol · L(-1)) and/or low pulmonary artery occlusion pressure (target 5-8 mmHg) were present, they received repeated boli of colloids (50 mL) as long as SV increased 10% or greater. Stroke volume and regional blood flows were monitored 2 min before and 30 min after fluid challenges. Of 132 fluid challenges, 45 (34%) resulted in an SV increase of 10% or greater, whereas 82 (62%) resulted in an increase of 10% or greater in one or more of the abdominal flows (P < 0.001). During blood flow redistribution, celiac trunk (19% of all measurements) and hepatic artery flow (15%) most often decreased, whereas portal vein (10%) and carotid artery (7%) flow decreased less frequently (P = 0.015, between regions). In control animals, celiac trunk (30% vs. 9%, P = 0.004) and hepatic artery (25% vs. 11%, P = 0.040) flow decreased more often than in endotoxin-infused pigs. Accordingly, blood flow redistribution is a common phenomenon in the postoperative period and is only marginally influenced by endotoxemia. Fluid management based on SV changes may not be useful for improving regional abdominal perfusion.

Gastrointestinal Function in Intensive Care Patients: Terminology, Definitions and Management. Recommendations of the ESICM Working Group on Abdominal Problems

Intensive Care Medicine. Mar, 2012  |  Pubmed ID: 22310869

Acute gastrointestinal (GI) dysfunction and failure have been increasingly recognized in critically ill patients. The variety of definitions proposed in the past has led to confusion and difficulty in comparing one study to another. An international working group convened to standardize the definitions for acute GI failure and GI symptoms and to review the therapeutic options.

Cancer Therapy Modulates VEGF Signaling and Viability in Adult Rat Cardiac Microvascular Endothelial Cells and Cardiomyocytes

Journal of Molecular and Cellular Cardiology. May, 2012  |  Pubmed ID: 22326847

This work was motivated by the incomplete characterization of the role of vascular endothelial growth factor-A (VEGF-A) in the stressed heart in consideration of upcoming cancer treatment options challenging the natural VEGF balance in the myocardium. We tested, if the cytotoxic cancer therapy doxorubicin (Doxo) or the anti-angiogenic therapy sunitinib alters viability and VEGF signaling in primary cardiac microvascular endothelial cells (CMEC) and adult rat ventricular myocytes (ARVM). ARVM were isolated and cultured in serum-free medium. CMEC were isolated from the left ventricle and used in the second passage. Viability was measured by LDH-release and by MTT-assay, cellular respiration by high-resolution oxymetry. VEGF-A release was measured using a rat specific VEGF-A ELISA-kit. CMEC were characterized by marker proteins including CD31, von Willebrand factor, smooth muscle actin and desmin. Both Doxo and sunitinib led to a dose-dependent reduction of cell viability. Sunitinib treatment caused a significant reduction of complex I and II-dependent respiration in cardiomyocytes and the loss of mitochondrial membrane potential in CMEC. Endothelial cells up-regulated VEGF-A release after peroxide or Doxo treatment. Doxo induced HIF-1α stabilization and upregulation at clinically relevant concentrations of the cancer therapy. VEGF-A release was abrogated by the inhibition of the Erk1/2 or the MAPKp38 pathway. ARVM did not answer to Doxo-induced stress conditions by the release of VEGF-A as observed in CMEC. VEGF receptor 2 amounts were reduced by Doxo and by sunitinib in a dose-dependent manner in both CMEC and ARVM. In conclusion, these data suggest that cancer therapy with anthracyclines modulates VEGF-A release and its cellular receptors in CMEC and ARVM, and therefore alters paracrine signaling in the myocardium.

Dexmedetomidine Vs Midazolam or Propofol for Sedation During Prolonged Mechanical Ventilation: Two Randomized Controlled Trials

JAMA. Mar, 2012  |  Pubmed ID: 22436955

Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an α(2)-agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort.

Effects of Cardiac Preload Reduction and Dobutamine on Hepatosplanchnic Blood Flow Regulation in Porcine Endotoxemia

American Journal of Physiology. Gastrointestinal and Liver Physiology. Jul, 2012  |  Pubmed ID: 22556139

Insufficient cardiac preload and impaired contractility are frequent in early sepsis. We explored the effects of acute cardiac preload reduction and dobutamine on hepatic arterial (Qha) and portal venous (Qpv) blood flows during endotoxin infusion. We hypothesized that the hepatic arterial buffer response (HABR) is absent during preload reduction and reduced by dobutamine. In anesthetized pigs, endotoxin or vehicle (n = 12, each) was randomly infused for 18 h. HABR was tested sequentially by constricting superior mesenteric artery (SMA) or inferior vena cava (IVC). Afterward, dobutamine at 2.5, 5.0, and 10.0 μg/kg per minute or another vehicle (n = 6, each) was randomly administered in endotoxemic and control animals, and SMA was constricted during each dose. Systemic (cardiac output, thermodilution) and carotid, splanchnic, and renal blood flows (ultrasound Doppler) and blood pressures were measured before and during administration of each dobutamine dose. HABR was expressed as hepatic arterial pressure/flow ratio. Compared with controls, 18 h of endotoxin infusion was associated with decreased mean arterial blood pressure [49 ± 11 mmHg vs. 58 ± 8 mmHg (mean ± SD); P = 0.034], decreased renal blood flow, metabolic acidosis, and impaired HABR during SMA constriction [0.32 (0.18-1.32) mmHg/ml vs. 0.22 (0.08-0.60) mmHg/ml; P = 0.043]. IVC constriction resulted in decreased Qpv in both groups; whereas Qha remained unchanged in controls, it decreased after 18 h of endotoxemia (P = 0.031; constriction-time-group interaction). One control and four endotoxemic animals died during the subsequent 6 h. The maximal increase of cardiac output during dobutamine infusion was 47% (22-134%) in controls vs. 53% (37-85%) in endotoxemic animals. The maximal Qpv increase was significant only in controls [24% (12-47%) of baseline (P = 0.043) vs. 17% (-7-32%) in endotoxemia (P = 0.109)]. Dobutamine influenced neither Qha nor HABR. Our data suggest that acute cardiac preload reduction is associated with preferential hepatic arterial perfusion initially but not after established endotoxemia. Dobutamine had no effect on the HABR.

A New Rabbit Model for the Study of Early Brain Injury After Subarachnoid Hemorrhage

Journal of Neuroscience Methods. Jul, 2012  |  Pubmed ID: 22595025

Pathophysiological disturbances during subarachnoid hemorrhage (SAH) and within the first few days thereafter are responsible for significant brain damage. Early brain injury (EBI) after SAH has become the focus of current research activities. The purpose of the present study was to evaluate whether a novel rabbit SAH model provokes EBI by means of neuronal degeneration, brain tissue death, and apoptosis in cerebral vascular endothelial cells.

The Role of Androgens on Hypoxia-inducible Factor (HIF)-1α-induced Angiogenesis and on the Survival of Ischemically Challenged Skin Flaps in a Rat Model

Microsurgery. Sep, 2012  |  Pubmed ID: 22707412

Effects of androgens on angiogenesis are controversial. Hypoxia-inducible factor (HIF)-1α promotes expression of vascular endothelial growth factor (VEGF) that stimulates angiogenesis.

Effect of Treatment Delay on Disease Severity and Need for Resuscitation in Porcine Fecal Peritonitis

Critical Care Medicine. Oct, 2012  |  Pubmed ID: 22890256

Early treatment in sepsis may improve outcome. The aim of this study was to evaluate how the delay in starting resuscitation influences the severity of sepsis and the treatment needed to achieve hemodynamic stability.

Effect of Remifentanil on Mitochondrial Oxygen Consumption of Cultured Human Hepatocytes

PloS One. 2012  |  Pubmed ID: 23028840

During sepsis, liver dysfunction is common, and failure of mitochondria to effectively couple oxygen consumption with energy production has been described. In addition to sepsis, pharmacological agents used to treat septic patients may contribute to mitochondrial dysfunction. This study addressed the hypothesis that remifentanil interacts with hepatic mitochondrial oxygen consumption. The human hepatoma cell line HepG2 and their isolated mitochondria were exposed to remifentanil, with or without further exposure to tumor necrosis factor-α (TNF-α). Mitochondrial oxygen consumption was measured by high-resolution respirometry, Caspase-3 protein levels by Western blotting, and cytokine levels by ELISA. Inhibitory κBα (IκBα) phosphorylation, measurement of the cellular ATP content and mitochondrial membrane potential in intact cells were analysed using commercial ELISA kits. Maximal cellular respiration increased after one hour of incubation with remifentanil, and phosphorylation of IκBα occurred, denoting stimulation of nuclear factor κB (NF-κB). The effect on cellular respiration was not present at 2, 4, 8 or 16 hours of incubation. Remifentanil increased the isolated mitochondrial respiratory control ratio of complex-I-dependent respiration without interfering with maximal respiration. Preincubation with the opioid receptor antagonist naloxone prevented a remifentanil-induced increase in cellular respiration. Remifentanil at 10× higher concentrations than therapeutic reduced mitochondrial membrane potential and ATP content without uncoupling oxygen consumption and basal respiration levels. TNF-α exposure reduced respiration of complex-I, -II and -IV, an effect which was prevented by prior remifentanil incubation. Furthermore, prior remifentanil incubation prevented TNF-α-induced IL-6 release of HepG2 cells, and attenuated fragmentation of pro-caspase-3 into cleaved active caspase 3 (an early marker of apoptosis). Our data suggest that remifentanil increases cellular respiration of human hepatocytes and prevents TNF-α-induced mitochondrial dysfunction. The results were not explained by uncoupling of mitochondrial respiration.

Randomized, Double-blind Trial of the Effect of Fluid Composition on Electrolyte, Acid-base, and Fluid Homeostasis in Patients Early After Subarachnoid Hemorrhage

Neurocritical Care. Feb, 2013  |  Pubmed ID: 22872427

Hyper- and hyponatremia are frequently observed in patients after subarachnoidal hemorrhage, and are potentially related to worse outcome. We hypothesized that the fluid regimen in these patients is associated with distinct changes in serum electrolytes, acid-base disturbances, and fluid balance.

Haemodynamic Variables and Functional Outcome in Hypothermic Patients Following Out-of-hospital Cardiac Arrest

Resuscitation. Jun, 2013  |  Pubmed ID: 23092896

To evaluate the association between haemodynamic variables during the first 24h after intensive care unit (ICU) admission and neurological outcome in out-of-hospital cardiac arrest (OHCA) victims undergoing therapeutic hypothermia.

Mitochondrial Function in Sepsis

European Journal of Clinical Investigation. May, 2013  |  Pubmed ID: 23496374

The relevance of mitochondrial dysfunction as to pathogenesis of multiple organ dysfunction and failure in sepsis is controversial. This focused review evaluates the evidence for impaired mitochondrial function in sepsis.

Effect of Sedation Level on the Prevalence of Delirium when Assessed with CAM-ICU and ICDSC

Intensive Care Medicine. Dec, 2013  |  Pubmed ID: 23921976

We hypothesized that reduced arousability (Richmond Agitation Sedation Scale, RASS, scores -2 to -3) for any reason during delirium assessment increases the apparent prevalence of delirium in intensive care patients. To test this hypothesis, we assessed delirium using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and Intensive Care Delirium Screening Checklist (ICDSC) in intensive care patients during sedation stops, and related the findings to the level of sedation, as assessed with RASS score.

No Evidence for a Local Renin-angiotensin System in Liver Mitochondria

Scientific Reports. 2013  |  Pubmed ID: 23959064

The circulating, endocrine renin-angiotensin system (RAS) is important to circulatory homeostasis, while ubiquitous tissue and cellular RAS play diverse roles, including metabolic regulation. Indeed, inhibition of RAS is associated with improved cellular oxidative capacity. Recently it has been suggested that an intra-mitochondrial RAS directly impacts on metabolism. Here we sought to rigorously explore this hypothesis. Radiolabelled ligand-binding and unbiased proteomic approaches were applied to purified mitochondrial sub-fractions from rat liver, and the impact of AngII on mitochondrial function assessed. Whilst high-affinity AngII binding sites were found in the mitochondria-associated membrane (MAM) fraction, no RAS components could be detected in purified mitochondria. Moreover, AngII had no effect on the function of isolated mitochondria at physiologically relevant concentrations. We thus found no evidence of endogenous mitochondrial AngII production, and conclude that the effects of AngII on cellular energy metabolism are not mediated through its direct binding to mitochondrial targets.

Different Contribution of Splanchnic Organs to Hyperlactatemia in Fecal Peritonitis and Cardiac Tamponade

BioMed Research International. 2013  |  Pubmed ID: 24228242

Changes in hepatosplanchnic lactate exchange are likely to contribute to hyperlactatemia in sepsis. We hypothesized that septic and cardiogenic shock have different effects on hepatosplanchnic lactate exchange and its contribution to hyperlactatemia.

Sedation Level and Prevalence of Delirium: Response to Brummel and Ely

Intensive Care Medicine. Jan, 2014  |  Pubmed ID: 24061632

Angiotensin II in Septic Shock: Effects on Tissue Perfusion, Organ Function, and Mitochondrial Respiration in a Porcine Model of Fecal Peritonitis

Critical Care Medicine. Aug, 2014  |  Pubmed ID: 24797374

To compare effects of norepinephrine and angiotensin II in experimental sepsis on hemodynamics, organ function, and mitochondrial respiration.

Interference of Angiotensin II and Enalapril with Hepatic Blood Flow Regulation

American Journal of Physiology. Gastrointestinal and Liver Physiology. Sep, 2014  |  Pubmed ID: 25059826

Acute reduction of portal vein blood flow (Qpv) increases hepatic arterial perfusion (Qha) [the hepatic arterial buffer response (HABR)]. Angiotensin II (AT-II) reduces Qpv, but its effect on HABR is not known. We explored interactions of AT-II and enalapril with hepatic blood flow regulation. Twenty healthy anesthetized pigs were randomized to receive AT-II (n = 8) from 5 to 61 ng/kg per min, enalapril (n = 8) from 3 to 24 μg/kg per h, or saline (n = 4). HABR was assessed by occluding portal vein and expressed as 1) ratio between changes in Qha and Qpv, 2) hepatic arterial conductance (Cha). AT-II infusion increased mean arterial blood pressure from 74 (66-77) mmHg to 116 (109-130) mmHg (median, IQR; P < 0.0001) and decreased cardiac output, Qpv, and renal artery flow (-24%, -28% and -45%, respectively). The fraction of cardiac output of Qha, carotid, and femoral flows increased. With enalapril, blood pressure decreased, whereas cardiac output was maintained with flow redistribution favoring hepatic and renal arteries. In AT-II group, dQha/dQpv increased from 0.06 (0.03, 0.17) to 0.24 (0.13, 0.31) (P = 0.002), but Cha during acute portal vein occlusion decreased from 4.3 (1.6, 6.6) to 2.9 (1.2, 3.7) ml/mmHg (P = 0.003). Both variables remained unchanged in the enalapril group and in controls. AT-II infusion reduces portal flow in parallel with cardiac output and induces a dose-dependent redistribution of flow, favoring brain, hepatic artery, and peripheral tissues at the expense of renal perfusion. During HABR, AT-II decreases Cha but increases Qha compensation, likely as result of increased hepatic arterial perfusion pressure. Enalapril had no effect on HABR.

Early Changes of Muscle Membrane Properties in Porcine Faecal Peritonitis

Critical Care (London, England). 2014  |  Pubmed ID: 25145497

Sepsis-induced myopathy and critical illness myopathy (CIM) are possible causes of muscle weakness in intensive care patients. They have been attributed to muscle membrane dysfunction. The aim of this study was to investigate membrane properties in the early stage of experimental sepsis by evaluating muscle excitability.

The Rabbit Shunt Model of Subarachnoid Haemorrhage

Translational Stroke Research. Dec, 2014  |  Pubmed ID: 25326333

Aneurysmal subarachnoid haemorrhage (SAH) is a disease with devastating complications that leads to stroke, permanent neurological deficits and death. Clinical and ex-perimental work has demonstrated the importance of the contribution of delayed cerebral vasospasm (DCVS) indepen-dent early events to mortality, morbidity and functional out-come after SAH. In order to elucidate processes involved in early brain injury (EBI), animal models that reflect acute events of aneurysmal bleeding, such as increase in intracranial pressure (ICP) and decrease in cerebral perfusion pressure, are needed. In the presented arterial shunt model, bleeding is initially driven by the pressure gradient between mean arterial blood pressure and ICP. SAH dynamics (flow rate, volume and duration) depend on physiological reactions and local anatomical intrathecal (cistern) conditions. During SAH, ICP reaches a plateau close to diastolic arterial blood pressure and the blood flow stops. Historical background, anaesthesia, perioperative care and monitoring, SAH induction, technical considerations and advantages and limitations of the rabbit blood shunt SAH model are discussed in detail. Awareness of technical details, physiological characteristics and appropriate monitoring methods guarantees successful implementation of the rabbit blood shunt model and allows the study of both EBI and DCVS after SAH.

Early Brain Injury Linearly Correlates with Reduction in Cerebral Perfusion Pressure During the Hyperacute Phase of Subarachnoid Hemorrhage

Intensive Care Medicine Experimental. Dec, 2014  |  Pubmed ID: 26266927

It is unclear how complex pathophysiological mechanisms that result in early brain injury (EBI) after subarachnoid hemorrhage (SAH) are triggered. We investigate how peak intracranial pressure (ICP), amount of subarachnoid blood, and hyperacute depletion of cerebral perfusion pressure (CPP) correlate to the onset of EBI following experimental SAH.

The Rabbit Blood Shunt Subarachnoid Haemorrhage Model

Acta Neurochirurgica. Supplement. 2015  |  Pubmed ID: 25366648

The recently introduced rabbit blood shunt subarachnoid haemorrhage model is based on the two standard procedures of subclavian artery cannulation and transcutaneous cisterna magna puncture. An extracorporeal shunt placed in between the arterial system and the subarachnoid space allows examiner-independent SAH in a closed cranium. Despite its straightforwardness, it is worth examining some specific features and characteristics of the model. We outline technical considerations to successfully perform the model with minimal mortality and morbidity. In addition, we discuss outcome measures, advantages and limitations, and the applicability of the model for the study of early brain injury and delayed cerebral vasospasm after SAH.

Impact of Early-onset Seizures on Grading and Outcome in Patients with Subarachnoid Hemorrhage

Journal of Neurosurgery. Feb, 2015  |  Pubmed ID: 25479126

After subarachnoid hemorrhage (SAH), seizure occurs in up to 26% of patients. The impact of seizure on outcome has been studied, yet its impact on grading is unknown. The authors evaluated the impact of early-onset seizures (EOS) on grading of spontaneous SAH and on outcome.

Esophageal Versus Surface Recording of Diaphragm Compound Muscle Action Potential

Muscle & Nerve. Apr, 2015  |  Pubmed ID: 25598146

Repeated diaphragm compound muscle action potential (CMAP) recordings may help to understand the pathophysiology of respiratory muscle weakness. Neurally adjusted ventilator assist (NAVA) uses esophageal EMG electrodes to drive the ventilator. We evaluated the feasibility of CMAP recordings using these electrodes and established normal values.

Dose Response of Endotoxin on Hepatocyte and Muscle Mitochondrial Respiration in Vitro

BioMed Research International. 2015  |  Pubmed ID: 25649304

Results on mitochondrial dysfunction in sepsis are controversial. We aimed to assess effects of LPS at wide dose and time ranges on hepatocytes and isolated skeletal muscle mitochondria.

Venous-arterial CO2 to Arterial-venous O2 Difference Ratio As a Resuscitation Target in Shock States?

Intensive Care Medicine. May, 2015  |  Pubmed ID: 25851389

Changes in Mitochondrial Enzymatic Activities of Monocytes During Prolonged Hypobaric Hypoxia and Influence of Antioxidants: A Randomized Controlled Study

Redox Report : Communications in Free Radical Research. Sep, 2015  |  Pubmed ID: 25867847

Exposure to high altitudes is associated with oxidative cellular damage due to the increased level of reactive oxygen and nitrogen species and altered activity of antioxidant systems. Subjects were submitted to prolonged hypoxia, to evaluate changes in mitochondrial enzyme activities of monocytes and their attenuation by supplementation with antioxidants.

Angiotensin II in Septic Shock

Critical Care (London, England). Mar, 2015  |  Pubmed ID: 25886853

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2015 and co-published as a series in Critical Care. Other articles in the series can be found online at Further information about the Annual Update in Intensive Care and Emergency Medicine is available from

Dexmedetomidine Versus Standard Care Sedation with Propofol or Midazolam in Intensive Care: an Economic Evaluation

Critical Care (London, England). Feb, 2015  |  Pubmed ID: 25887576

Dexmedetomidine was shown in two European randomized double-blind double-dummy trials (PRODEX and MIDEX) to be non-inferior to propofol and midazolam in maintaining target sedation levels in mechanically ventilated intensive care unit (ICU) patients. Additionally, dexmedetomidine shortened the time to extubation versus both standard sedatives, suggesting that it may reduce ICU resource needs and thus lower ICU costs. Considering resource utilization data from these two trials, we performed a secondary, cost-minimization analysis assessing the economics of dexmedetomidine versus standard care sedation.

Do Different Anesthesia Regimes Affect Hippocampal Apoptosis and Neurologic Deficits in a Rodent Cardiac Arrest Model?

BMC Anesthesiology. Jan, 2015  |  Pubmed ID: 25972075

Different anesthesia regimes are commonly used in experimental models of cardiac arrest, but the effects of various anesthetics on clinical outcome parameters are unknown. We conducted a study in which we subjected rats to cardiac arrest under medetomidine/ketamine or sevoflurane/fentanyl anesthesia.

Reconsidering the Logic of World Federation of Neurosurgical Societies Grading in Patients with Severe Subarachnoid Hemorrhage

Journal of Neurosurgery. Feb, 2016  |  Pubmed ID: 26381248

Current data show a favorable outcome in up to 50% of patients with World Federation of Neurosurgical Societies (WFNS) Grade V subarachnoid hemorrhage (SAH) and a rather poor prediction of worst cases. Thus, the usefulness of the current WFNS grading system for identifying the worst scenarios for clinical studies and for making treatment decisions is limited. One reason for this lack of differentiation is the use of "negative" or "silent" diagnostic signs as part of the WFNS Grade V definition. The authors therefore reevaluated the WFNS scale by using "positive" clinical signs and the logic of the Glasgow Coma Scale as a progressive herniation score.

Prognostic and Diagnostic Value of EEG Signal Coupling Measures in Coma

Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. Aug, 2016  |  Pubmed ID: 26578462

Our aim was to assess the diagnostic and predictive value of several quantitative EEG (qEEG) analysis methods in comatose patients.

Gastrointestinal Failure in the ICU

Current Opinion in Critical Care. Apr, 2016  |  Pubmed ID: 26835609

The current review summarizes different aspects of assessment of gastrointestinal function and provides a practical approach to management of adult patients with gastrointestinal dysfunction in the ICU.

Anaesthetic Induction with Etomidate in Cardiac Surgery: A Randomised Controlled Trial

European Journal of Anaesthesiology. Jun, 2016  |  Pubmed ID: 26914224

Etomidate is perceived as preserving haemodynamic stability during induction of anaesthesia. It is also associated with adrenocortical dysfunction. The risk/benefit relationship is controversial.

The Effects of Fentanyl on Hepatic Mitochondrial Function

Anesthesia and Analgesia. Aug, 2016  |  Pubmed ID: 27089001

Remifentanil interferes with hepatic mitochondrial function. The aim of the present study was to evaluate whether hepatic mitochondrial function is affected by fentanyl, a more widely used opioid than remifentanil.

Effect of PEEP, Blood Volume, and Inspiratory Hold Maneuvers on Venous Return

American Journal of Physiology. Heart and Circulatory Physiology. Sep, 2016  |  Pubmed ID: 27422991

According to Guyton's model of circulation, mean systemic filling pressure (MSFP), right atrial pressure (RAP), and resistance to venous return (RVR) determine venous return. MSFP has been estimated from inspiratory hold-induced changes in RAP and blood flow. We studied the effect of positive end-expiratory pressure (PEEP) and blood volume on venous return and MSFP in pigs. MSFP was measured by balloon occlusion of the right atrium (MSFPRAO), and the MSFP obtained via extrapolation of pressure-flow relationships with airway occlusion (MSFPinsp_hold) was extrapolated from RAP/pulmonary artery flow (QPA) relationships during inspiratory holds at PEEP 5 and 10 cmH2O, after bleeding, and in hypervolemia. MSFPRAO increased with PEEP [PEEP 5, 12.9 (SD 2.5) mmHg; PEEP 10, 14.0 (SD 2.6) mmHg, P = 0.002] without change in QPA [2.75 (SD 0.43) vs. 2.56 (SD 0.45) l/min, P = 0.094]. MSFPRAO decreased after bleeding and increased in hypervolemia [10.8 (SD 2.2) and 16.4 (SD 3.0) mmHg, respectively, P < 0.001], with parallel changes in QPA Neither PEEP nor volume state altered RVR (P = 0.489). MSFPinsp_hold overestimated MSFPRAO [16.5 (SD 5.8) vs. 13.6 (SD 3.2) mmHg, P = 0.001; mean difference 3.0 (SD 5.1) mmHg]. Inspiratory holds shifted the RAP/QPA relationship rightward in euvolemia because inferior vena cava flow (QIVC) recovered early after an inspiratory hold nadir. The QIVC nadir was lowest after bleeding [36% (SD 24%) of preinspiratory hold at 15 cmH2O inspiratory pressure], and the QIVC recovery was most complete at the lowest inspiratory pressures independent of volume state [range from 80% (SD 7%) after bleeding to 103% (SD 8%) at PEEP 10 cmH2O of QIVC before inspiratory hold]. The QIVC recovery thus defends venous return, possibly via hepatosplanchnic vascular waterfall.

Control Groups in Recent Septic Shock Trials: a Systematic Review

Intensive Care Medicine. Dec, 2016  |  Pubmed ID: 27448676

The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials.

Targeted Tissue Perfusion Versus Macrocirculation-guided Standard Care in Patients with Septic Shock (TARTARE-2S): Study Protocol and Statistical Analysis Plan for a Randomized Controlled Trial

Trials. Aug, 2016  |  Pubmed ID: 27484695

Septic shock has a 90-day mortality risk of up to 50 %. The hemodynamic targets, including mean arterial pressure (MAP) are not based on robust clinical data. Both severe hypotension and high doses of vasopressors may be harmful. Hence, re-evaluation of hemodynamic targets in septic shock is relevant.

Effects of Early, Combined Endurance and Resistance Training in Mechanically Ventilated, Critically Ill Patients: a Study Protocol for a Randomised Controlled Trial

Trials. Aug, 2016  |  Pubmed ID: 27527501

Prolonged need for intensive care is associated with neuromuscular weakness, termed Intensive Care Unit Acquired Weakness. Those affected suffer from severe functional impairment that can persist for years. First studies suggest a positive effect of physiotherapy and early mobilisation. However, the ideal intervention for a preferential functional outcome is not known. So far no randomised controlled trial has been conducted to specifically evaluate an early endurance and resistance training in the mechanically ventilated, critically ill patient.

Evolution of Blood Lactate and 90-Day Mortality in Septic Shock. A Post Hoc Analysis of the Finnaki Study

Shock (Augusta, Ga.). Oct, 2016  |  Pubmed ID: 27755509

Hyperlactatemia predicts mortality in patients with sepsis and septic shock, and its normalization is a potential treatment goal. We investigated the association of blood lactate and its changes over time with 90-day mortality in septic shock. We performed a post hoc analysis of 513 septic shock patients with admission blood lactate measurements in the prospective, observational, multicenter FINNAKI study. Repetitive lactate measurements were available in 496 patients for analyses of change in lactate values during ICU stay.The 90-day mortality for all patients was 33.3%. Patients with admission lactate > 2 mmol/L had higher 90-day mortality than those with admission lactate ≤ 2 mmol/L (43.4% vs. 22.6%, p < 0.001). Patients with persistent hyperlactatemia (> 2 mmol/L) at ≥ 72 hours had higher 90-day mortality compared to those with a lactate value of ≤ 2.0 mmol/L (52.0% vs. 24.3%, p < 0.001). Time-weighted mean lactate values were higher in non-survivors than in survivors, (median [IQR] 2.05 [1.38-4.22] mmol/L vs. 1.29 [0.98-1.77] mmol/L, p < 0.001). Time to normalization of lactate was comparable for 90-day non-survivors and survivors (median [IQR] 17.0 [3.5-43.5] vs. 15.0 [5.0-35.0] hours, p = 0.67). In separate models, time-weighted mean lactate, lactate value at ≥ 72 hours, and hyperlactatemia at ≥ 72 hours were independently associated with 90-day mortality, but admission lactate and time to normalization of lactate were not. These findings may inform future clinical trials using combined surrogate endpoints for mortality in septic shock patients.

The Impact of Extracerebral Organ Failure on Outcome of Patients After Cardiac Arrest: an Observational Study from the ICON Database

Critical Care (London, England). Nov, 2016  |  Pubmed ID: 27839517

We used data from a large international database to assess the incidence and impact of extracerebral organ dysfunction on prognosis of patients admitted after cardiac arrest (CA).

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