A 24-h work shift in intensive care personnel: biological pathways between work stress and ill health.

This study evaluated inflammatory, coagulation and microvascular responses to a continuous 24-h work day in 13 healthy intensive care physicians. Inflammatory markers (interleukin [IL]-2, IL-6, IL-10, tumour necrosis factor-α, matrix metalloproteinase [MMP]-9 and adiponectin), adhesion molecules (vascular cellular adhesion molecule-1 and intercellular adhesion molecule-1 [ICAM-1]), coagulation parameters (thrombin-anti thrombin, von Willebrand factor and tissue factor) and sublingual micro circulation were assessed before and after a 24-h work shift. The 24-h work shift had no effect on inflammatory markers and ICAM-1. Direct visualization of micro-circulation did not reveal stress-related perfusion abnormalities. A 24-h work shift in the intensive care unit was associated with significantly increased plasma levels of tissue factor - a potentially important mechanism linking acute job strain, haemostasis and atherosclerosis. The long-term consequences warrant further evaluation.

Tissue concentrations of vasoactive intestinal peptide are affected by peritonitis-induced sepsis and hemofiltration in pigs.

Vasoactive intestinal peptide (VIP) is a neuropeptide released from the autonomic nerves exerting multiple antiinflammatory effects. The aim of the present study was to investigate the impact of severe sepsis and hemofiltration in two settings on plasma and tissue concentrations of VIP in a porcine model of sepsis. Thirty-two pigs were divided into 5 groups: 1) control group; 2) control group with conventional hemofiltration; 3) septic group; 4) septic group with conventional hemofiltration; 5) septic group with high-volume hemofiltration. Sepsis induced by faecal peritonitis continued for 22 hours. Hemofiltration was applied for the last 10 hours. Hemodynamic, inflammatory and oxidative stress parameters (heart rate, mean arterial pressure, cardiac output, systemic vascular resistance, plasma concentrations of tumor necrosis factor-alpha, interleukin-6, thiobarbituric acid reactive species, nitrate + nitrite, asymmetric dimethylarginine) and the systemic VIP concentrations were measured before faeces inoculation and at 12 and 22 hours of peritonitis. VIP tissue levels were determined in the left ventricle, mesenteric and coronary arteries. Sepsis induced significant increases in VIP concentrations in the plasma and mesenteric artery, but it decreased peptide levels in the coronary artery. Hemofiltration in both settings reduced concentrations of VIP in the mesenteric artery. In severe sepsis, VIP seems to be rapidly depleted from the coronary artery and, on the other hand, upregulated in the mesenteric artery. Hemofiltration in both settings has a tendency to drain away these upregulated tissue stores which could result in the limited secretory capacity of the peptide.

New developments in septic acute kidney injury.

The kidney is a common "victim organ" of various insults in critically ill patients. Sepsis and septic shock are the dominant causes of acute kidney injury, accounting for nearly 50 % of episodes of acute renal failure. Despite our substantial progress in the understanding of mechanisms involved in septic acute kidney injury there is still a huge pool of questions preclusive of the development of effective therapeutic strategies. This review briefly summarizes our current knowledge of pathophysiological mechanisms of septic acute kidney injury focusing on hemodynamic alterations, peritubular dysfunction, role of inflammatory mediators and nitric oxide, mitochondrial dysfunction and structural changes. Role of proteomics, new promising laboratory method, is mentioned.

The effects of short-term norepinephrine up-titration on hemodynamics in cardiogenic shock.

A higher mean arterial pressure (MAP) achieved by norepinephrine up-titration may improve organ blood flow in critically ill, whereas norepinephrine-induced afterload rise might worsen myocardial function. Our aim was to assess the effects of norepinephrine dose titration on global hemodynamics in cardiogenic shock. We prospectively evaluated 12 mechanically ventilated euvolemic patients (aged 67 +/- 12 years) in cardiogenic shock (10 patients acute myocardial infarction, 1 patient dilated cardiomyopathy, 1 patient decompensated aortic stenosis). Hemodynamic monitoring included arterial and Swan-Ganz catheters. The first data were obtained at MAP of 65 mm Hg, then the norepinephrine dose was increased over 40 min to achieve MAP of 85 mm Hg. Finally, the norepinephrine-dose was tapered over 40 min to achieve MAP of 65 mm Hg. Norepinephrine up-titration increased MAP to the predefined values in all patients with concomitant mild increase in filling pressures and heart rate. Systemic vascular resistance increased, whereas cardiac output remained unchanged. During norepinephrine down-titration, all hemodynamic parameters returned to baseline values. We observed no changes in lactate levels and mixed venous oxygen saturation. Our data suggest that short-term norepinephrine dose up-titration in cardiogenic shock patients treated or pretreated with inotropes was tolerated well by the diseased heart.

[24-year old male with fever, multi-organ dysfunction and fast progressing ARDS]. / 24letý muz s horeckami, multiorgánovou dysfunkcí a rychle progredujícím ARDS.

A 24-year-old man presented with cough, sore throat, fever, maculopapulous exanthema, pericardial and pleural effusion. Despite extensive evaluation neither infectious, autoimmune, hematological nor oncological disorders were revealed. Broad spectrum antibiotic and subsequently corticosteroid treatment failed to resolve the symptoms. Multiorgan failure with rapid progress of acute respiratory distress syndrome and circulatory failure developed and patient died. Adult onset Still's disease (AOSD), a diagnosis considered in this patient, is a rare disease with unknown prevalence, pathogenesis and etiology. Clinically it is characterized by spiking fever, arthritis, rash, and impairment of multiple organs. There is no single diagnostic test for AOSD. Rather, the diagnosis is based on the clinical criteria and requires the exclusion of infectious, neoplastic, and other autoimmune diseases. Rarely the course of the disease can be rapidly progressive to death. Treatment includes the use of non-steroid antirheumatic drugs and corticosteroids. Limited data suggest that biological agents (e.g. anti-TNF-alpha, anti-IL-1), rituximab or intravenous immunoglobulins might be promising for the treatment of severe cases.

[Persistent diarrhoea, hypotension, polyneuropathy]. / Perzistentní prujmy, hypotenze a polyneuropatie.

We present a case report of a 59-year-old man with a history of arterial hypertension and excision of malignant melanoma. He was admitted to the hospital because of two months history of diarrhoea, weight loss and circulatory collapse. In addition, the patient suffered from marked vegetative instability with symptomatic hypotension, polyneuropathy and progression of renal insufficiency, without proteinuria. Complex examination did not reveal neoplasms, endocrine, autoimmune, infectious or neurodegenerative disorders. A serial biopsy of colon failed to provide a clue to the diagnosis. However, AA amyloidosis was found on the kidney biopsy. Neither chronic inflammation nor malignancy was revealed and, hence, no causal treatment could have been established. The patient died from multiple organ failure. The autopsy confirmed systemic AA amyloidosis. The triad consisting ofdiarrhoea, polyneuropathy and hypotension should rise the suspicion on amyloidosis.

[Hemopurification in sepsis: current view]. / Hemoeliminacní metody v lécbe sepse: soucasný stav.

Sepsis is the leading cause of mortality in non-coronary intensive care units. The uncontrolled and deregulated systemic inflammatory response to infection plays a central role in the pathophysiology of sepsis. This response is mediated by a broad spectrum of endogenous mediators leading to dysfunction in multiple organs remote from the primary infectious site. The failure of numerous clinical trials aimed at eliminating a single mediator stimulated the research to focus on non-selective removal of excessively produced mediators of sepsis. This "detoxification" forms the theoretical basis and biological rationale for the use of hemopurification therapies as an adjunctive treatment of sepsis. Our article reviews the current evidence of hemopurification methods in the supportive treatment of sepsis, briefly discusses new trends and summarizes the recommendations for clinical practice.

[Feedings of critical care patients by endoscopic three-luminal tube--a retrospective analysis]. / Výziva kriticky nemocných endoskopicky zavádenou trojluminální sondou--retrospektivní analýza.

BACKGROUND: Enteral nutrition (EN) represents a preferred type of nutritional support in critical care patients, in spite of the high incidence of intolerance. One of the methods which can speed up the delivery of adequate amounts of food is to switch from the gastric to post-pyloric feeding. A three-luminal tube (TLT) enables post-pyloric enteral feeding with accompanying gastric decompression. The aim of our study was to evaluate effectiveness and safety of the endoscopically introduced TLT along with the estimation of the adequate dose of enteral nutrition. METHODS AND RESULTS: Retrospective analysis of 111 critical care patients with 140 introduced TLT during 2003 to 2006 in two intensive care units (UIC) in the Teaching hospital in Plzen included patients of average age 54 years (+/- 15), APACHE II score 26 (+/- 10) and UIC mortality was 24%. Eight introductions were technically not successful (6%). Reintroduction of the tube was necessary in 21 patients (19%). The average time of tube introduction was 6 minutes (+/- 3). In direct relation to endoscopy no serious complication was observed. In our cohort, 34 ventilator-associated pneumonias developed (31%). Average time interval since the admission to the hospital till TLT introduction was 7 days (+/- 6). Evaluation of a subgroup of 77 patients from one UIC has shown that the adequate amount of EN was achieved in 82% of patients in 4 days (+/- 3) after the TLT introduction. In average, TLT was introduced for 11 days (+/- 7). CONCLUSIONS: Endoscopic TLT introduction represents a safe and reliable method which can ensure adequate amount of enteral nutrition in majority of critical care patients with gastrointestinal dysfunction. In our conditions, TLT is probably not sufficiently used.

Perfusion pressure manipulation in porcine sepsis: effects on intestinal hemodynamics.

Limited information is available about selection of the threshold for arterial blood pressure in critically ill patients, particularly in sepsis when normal organ blood flow autoregulation may be altered. The present experimental study investigated whether increasing perfusion pressure using norepinephrine in normotensive hyperdynamic porcine bacteremia affects intestinal macro- and microcirculation. Nine pigs received continuous i.v. administration of Pseudomonas aeruginosa (PSAE) to develop hyperdynamic, normotensive (mean arterial pressure [MAP] 65 mm Hg) sepsis. Norepinephrine was used to achieve 10-15 % increase in MAP. Mesenteric arterial blood flow (Q(gut)), ileal mucosal microvascular perfusion (LDF(gut)) and ileal-end-tidal PCO(2) gap (PCO(2) gap) were measured before norepinephrine, after 60 min of norepinephrine infusion and 60 min after norepinephrine infusion had been discontinued. During a 12 h period of PSAE infusion all pigs developed hyperdynamic circulation with significantly decreased MAP. Although the mesenteric blood flow remained unchanged, infusion of PSAE resulted in a gradual fall of ileal microvascular perfusion, which was associated with progressively rising PCO(2) gap. Norepinephrine which induced a 10-15 % increase in perfusion pressure (i.e. titrated to attain near baseline values of MAP) affected neither Q(gut) nor the intestinal blood flow distribution (Q(gut)/CO). Similarly, norepinephrine did not change either LDF(gut) or PCO(2) gap. In this hyperdynamic, normotensive porcine bacteremia, norepinephrine-induced increase in perfusion pressure exhibited neither beneficial nor deleterious effects on intestinal macrocirculatory blood flow and ileal mucosal microcirculation. The lack of changes suggests that the gut perfusion was within its autoregulatory range.

Fluid challenge in patients at risk for fluid loading-induced pulmonary edema.

BACKGROUND: This study evaluated the effects of protocol-guided fluid loading on extravascular lung water (EVLW) and hemodynamics in a group of patients at high risk for volume expansion-induced pulmonary and systemic edema. METHODS: Nine acutely admitted septic patients with acute lung injury (ALI) were prospectively studied. In addition to sepsis and ALI, the following criteria indicating increased risk for edema formation had to be fulfilled: increased vascular permeability defined as microalbuminuria greater than fivefold normal and hypoalbuminemia < 30 g l(-1). Two hundred-ml boluses of a 10% hydroxyethyl starch (HES) was titrated to obtain best filling pressure/stroke volume relation. Extravascular lung water and intrathoracic blood volume (ITBV) were measured using a transpulmonary double-indicator dilution technique. Baseline data were compared with data at the end of fluid loading and 3 h postchallenge. RESULTS: At study entry the mean EVLW was 13 ml kg(-1), and the mean EVLW/ITBV ratio (indicator of pulmonary permeability) was 0.72 (normal range 0.20-0.30). To attain optimal preload/stroke volume relation 633 +/- 240 ml of HES was needed. Fluid loading significantly increased preload (CVP, PAOP and ITBV), and stroke volume. Effective pulmonary capillary pressure (Pcap) rose only slightly. As a result, the Pcap-PAOP gradient decreased. Despite increased cardiac output, EVLW did not change by plasma expansion. CONCLUSION: In this selected group of at-risk patients, the optimization of cardiac output guided by the concept of best individual filling pressure/stroke volume relationship did not worsen permeability pulmonary edema.

[Rhabdomyolysis--development, causes, sequelae and therapy]. / Rabdomyolýza--mechanismy vzniku, príciny, dusledky a lécba.

Rhabdomyolysis is a syndrome characterized by striated muscle necrosis and the release of intracellular muscle constituents into the circulation. The severity of illness ranges from asymptomatic elevations of muscle enzymes in the serum to life-threatening cases associated with extreme enzyme elevations, electrolyte imbalances, and acute renal failure. This chapter reviews recent knowledge of pathophysiologic mechanisms leading to myocytes injury, diseases its causes, consequences and treatment options. Particular attention is focused on rhabdomyolysis in critically ill patients.

[Acute kidney failure in critically ill patients and its prevention]. / Akutní selhání ledvin u kriticky nemocných a moznosti jeho prevence.

Acute renal failure often complicates the course of critically illness and can contribute to high morbidity and mortality. In most cases acute renal failure represents a part of the multiple organ dysfunction syndrome and it is usually related to the ischemic and/or toxic injury of tubular cells (acute tubular necrosis, ATN). The presented paper reviews the mechanisms involved in this two types of tubular cells injury. It analyzes the measures of kidney protection during critical illness, which include optimization of systemic and intrarenal hemodynamics as well as avoidance of nephrotoxic drugs. It describes the most common nephrotoxic drugs and proposes principles of their safer use. Potential strategies to stimulate kidney function recovery are also discussed.

Enteral nutrition and hepatosplanchnic region in critically ill patients - friends or foes?

Enteral nutrition (EN) is a preferred way of feeding in critically ill patients unless obvious contraindications such as ileus or active gastrointestinal bleeding are present. Early enteral nutrition as compared to delayed EN or total parenteral nutrition decreases morbidity in postsurgical and trauma patients. The hepatosplanchnic region plays a pivotal role in the pathophysiology of sepsis and multiple organ dysfunction syndrome. The beneficial effects of EN on splanchnic perfusion and energy metabolism have been documented both in healthy volunteers and animal models of sepsis, hemorrhagic shock and burns. By contrast, EN may increase splanchnic metabolic demands, which in turn may lead to oxygen and/or energy demand/supply mismatch, especially when hyperemic response to EN is not preserved. Therefore, the timing of initiation and the dose of EN in patients with circulatory failure requiring vasoactive drugs are a matter of controversy. Interestingly, the results of recent clinical studies suggest that early enteral nutrition may not be harmful even in patients with circulatory compromise. Nevertheless, possible onset of serious complications, the non-occlusive bowel necrosis in particular, have to be kept in mind. Unfortunately, there is only a limited number of clinically applicable monitoring tools for the effects of enteral nutrition in critically ill patients.

Continuous venovenous hemofiltration: effects on monocyte and lymphocyte immunophenotype in critically ill patients.

The aim of this study was to test the hypothesis that continuous venovenous hemofiltration (CVVH) increases HLA-DR expression on monocytes and T lymphocytes in critically ill patients. 24 septic (SP) and 10 non-septic (NSP) medical ICU patients with acute renal failure were studied prospectively. The ultrafiltration rate was 20-30 ml.kg(-1).h(-1). The total and differential white cell counts were measured and CD3+ lymphocyte count, HLA-DR expression on CD14+ monocytes and CD3+ lymphocytes were analysed by two-colour flow cytometry before, 4 and 24 h after CVVH initiation, respectively. CVVH did not influence leukocyte, granulocyte, total lymphocyte and CD3+ lymphocyte counts in both groups of patients. The percentage of HLA-DR+/CD14+ monocytes in SP revealed no changes, whereas it decreased after 4 h of CWH in NSP (p < 0.05). The percentage of HLA-DR+/CD3+ lymphocytes in SP decreased after 24 h (p < 0.05), whereas it remained unchanged in NSP. We conclude that CWH initiation is not associated with the increase of HLA-DR expression on CD14+ monocytes and T lymphocytes in critically ill patients with acute renal failure.

[Fluid resuscitation in conditions with disorders of capillary permeability]. / Tekutinová resuscitace u stavu s narusenou kapilární permeabilitou.

Fluid resuscitation remains a cornerstone in the treatment of various types of circulatory failure. Alterations in microvascular permeability are a hallmark of a number of inflammatory conditions including sepsis, septic shock, burns and the acute respiratory distress syndrome. As a result, the loss of plasma fluid into the interstitial space leads to hypovolaemia and tissue hypoperfusion. Administration of large volumes of fluids in often necessary to restore the nutritional blood flow to tissues. This strategy, however, involves the risk of interstitial edema formation, which in turn may further impair tissue oxygen distribution. The presented paper briefly reviews the principles of transvascular fluid exchange and the pathophysiology of capillary permeability. It discusses the ongoing controversy on the optimal way and the end points of volume replacement as well as the choice of fluid in conditions associated with capillary leakage.

The effect of heparin rinse on the biocompatibility of continuous veno-venous hemodiafiltration.

UNLABELLED: The aims of our cross-over randomized study were (1) to assess hemostasis in patients with acute renal failure (ARF) and (2) to determine whether or not the generally recommended heparin rinse of the extracorporeal circuit (ECC) prior to the procedure affects thrombogenicity, complement activation, and leukocyte count in blood during continuous venovenous hemodiafiltration (CVVHDF). Eleven critically ill ARF patients were treated, in random order, using CVVHDF in postdilution setup following ECC rinse with saline (A) with heparin at a concentration of 2,000 IU/L (10 procedures), (B) with heparin at a concentration of 10,000 IU/L (7 procedures), and (C) without heparin (9 procedures). Except for the rinse, anticoagulation therapy did not differ in individual patients during the procedures. Blood was withdrawn before, and at minutes 15, 60, and 360 invariably at diafilter inlet and outlet. Compared with healthy individuals, patients showed lower blood thrombocyte counts (153 vs 233*10(9)/L, p<0.01, arithmetic means, Student's t test), longer aPTT (44 vs 36 s, p<0.05), higher plasma levels of heparin (0.1 vs 0.0 U/mL, p<0.05), D-dimer (1129 vs 36 ng/mL, p<0.001) and beta-thromboglobulin (BTG) (159 vs 37 U/mL, p<0.001) prior to CVVHDF. The comparison of procedures with different rinsing technique did not reveal any significant difference in their effects on blood thrombocyte and leukocyte counts, aPTT, plasma levels of heparin, BTG, thrombin-antithrombin III complexes, D-dimer, or the C5a complement component. CONCLUSIONS: (1) Patients indicated for CVVHDF show impaired hemostasis involving thrombocytes, coagulation, and fibrinolysis, (2) no beneficial effect of heparin rinse on CVVHDF ECC thrombogenicity, complement activation or blood leukocyte counts was demonstrated.

[Gastrointestinal tract dysfunction in critical illness]. / Dysfunkce gastrointestinálního traktu u kriticky nemocných.

Until relatively recently, the gastrointestinal (GI) tract was considered a dormant, metabolically and immunologically inactive organ in critically illnesses. However, the GI tract provides a number of crucial functions that, in fact, may influence morbidity and mortality of many critically ill patients. Its large absorptive area provides a site for nutrient digestion and utilization and serves as an important barrier preventing the systemic absorption of intraluminal microbes and its toxic products. Moreover, the GI tract is the largest reservoir of lymphocytes in the body, which significantly contribute to the immune response of the critically ill patients. The gut dysfunction occurs frequently and early in the intensive care patients. Abnormal colonization, impaired intestinal epithelial barrier function and bacterial translocation represent the key components of gut failure implicating in the pathogenesis of sepsis and multiorgan dysfunction. This review summarizes recent insights into the role of the gut in critically ill patients with particular focus on 1) the basis of "gut-origin hypothesis", 2) pathophysiology of gut dysfunction, 3) monitoring of intestinal function, and 4) protective measures and novel therapeutic strategies.

Submaximal exercise in healthy volunteers: the relationship between gastric mucosal and systemic energy status.

The effect of exercise on gastric mucosal energy status has not been fully elucidated. The aim of this study was to evaluate the impact of submaximal cycling on gastric mucosal energy balance and its relationship to changes in systemic energy status. Ten healthy volunteers (age 20-40 years) were investigated at rest (BL), during 30 min of submaximal exercise (E) on bicycle ergometry and during the 30 min after the completion of cycling. Gastric mucosal PCO(2) ( P(gm)CO(2)) was measured by air tonometry at 10-min intervals and the gastric mucosal-arterial PCO(2) difference ( PCO(2)gap) was calculated. Hemodynamics, arterial blood gases, lactate and pyruvate were also measured. PCO(2)gap significantly increased throughout exercise [BL: 0.2 kPa (median), -0.1-0.6 kPa (25th-75th percentiles); E(10 min): 1.0 kPa, 0.8-1.7 kPa; E(20 min): 1.35 kPa, 0.8-1.8 kPa; E(30 min): 1.5 kPa, 0.9-2.0 kPa]. The early changes in PCO(2)gap ( PCO(2)gap at E(10 min) minus PCO(2)gap at BL) correlated significantly and positively with corresponding changes in arterial lactate ( r(2)=0.58, P<0.05) and lactate-to-pyruvate ratio ( r(2)=0.72, P<0.05). On recovery, all metabolic parameters normalized within 30 min. We conclude that submaximal cycling in volunteers leads to the early derangement of gastric mucosal energy balance. The time course of PCO(2)gap parallels changes in systemic energy status.