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Biomedical subjects

J Briegel

Publications and source records attributed to J Briegel.

At least 19 recordsLinked to original sources

Association between vasopressor dependence and early outcome in patients after cardiac surgery.

Arterial hypotension with vasopressor dependence is a major problem after cardiac surgery. We evaluated the early postoperative course of 1558 consecutive patients scheduled for cardiac surgery, and compared the outcome of patients with and without vasopressor dependence (defined as the need for > 0.1 microg x kg(-1) x h(-1) noradrenaline for > 3 h in the face of normovolaemia). Vasopressor dependence was diagnosed in 424 patients (27%) and was associated with a higher incidence of postoperative renal failure (67 (15.7%) vs 7 (0.6%), respectively; p < 0.0001), a longer duration of ventilation (median IQR [range]) 14 (8-26 [6-39]) h vs 8 (5-11 [4-32]) h; p < 0.0001), a greater need for red cell transfusion (3 (1-5 [0-10]) units vs 1 (0-2 [0-4]) units; p < 0.001) and a longer length of stay in the ICU (4 (2-6 [2-9] days) vs 2 (1-3 [1-6] days; p < 0.001). Vasopressor dependence could be predicted from a combination of factors, including pre-operative ejection fraction < 37%, cardiopulmonary bypass lasting > 94 min, and postoperative interleukin-6 > 837 pg x ml(-1).

Aged↗

Hemofiltration does not influence early S-100B serum levels in septic shock patients receiving stress doses of hydrocortisone or placebo.

BACKGROUND: The prognosis in patients with hyperdynamic septic shock correlates with the presence and the severity of septic encephalopathy. However, the neurological evaluation is considerably influenced by the use of analgesia sedation during mechanical ventilation. An early concentration peak of the neuroprotein S-100B in serum reflects both cellular damage at an increased permeability of the blood-brain-barrier and a delayed renal elimination. Thus, the objective of this study was to analyze the effect of continuous veno-venous hemofiltration (CVVH) on early S-100B serum levels in septic shock patients, who were treated with either stress doses of hydrocortisone or placebo. METHODS: Twenty-four consecutive patients, who met the ACCP / SCCM criteria for septic shock, were enrolled in this prospective, randomised, double-blind, single-center trial. The severity of illness at recruitment was graded using the APACHE II and SAPS II scoring systems; the MODS was described by the SOFA score. All patients were prospectively randomised to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started in 12 patients with a loading dose of 100 mg and followed by a continuous infusion of 0.18 mg/kg/h for 6 days. RESULTS: Median S-100B serum levels of the hydrocortisone group decreased from 0.32 ng/ml (0.19-3.60) at study entry to 0.07 ng/ml (0.04 - 0.32) 6 days later without significant differences compared to the placebo group. Patients undergoing CVVH showed significantly higher S-100B serum values compared to patients without CVVH (p<0.001). However, initial median S-100B serum levels of the CVVH group even increased from 0.92 ng/ml (0.16 - 4.63) to 2.33 ng/ml (0.59 - 2.44) 30 hours after study entry, reaching data ranges already known in patients with out-of-hospital cardiac arrest or severe traumatic brain injury. CONCLUSION: Early S-100B serum levels in septic shock patients receiving either stress doses of hydrocortisone or placebo were not influenced by CVVH. For the first time, we observed a similar extent of S-100B serum increase in CVVH patients, who had significantly higher S-100B serum values compared to those without CVVH, as reported for out-of-hospital cardiac arrest or severe traumatic brain injury. Hypercortisolemia induced by the infusion of stress doses of hydrocortisone did not significantly reduce early S-100B serum concentrations with time.

Adult↗

Hemofiltrastion does not influence early S-100B serum levels in septic shock patients receiving stress doses of hydrocortisone or placebo.

BACKGROUND: The prognosis in patients with hyperdynamic septic shock correlates with the presence and the severity of septic encephalopathy. However, the neurological evaluation is considerably influenced by the use of analgesia sedation during mechanical ventilation. An early concentration peak of the neuroprotein S-100B in serum reflects both cellular damage at an increased permeability of the blood-brain-barrier and a delayed renal elimination. Thus, the objective of this study was to analyze the effect of continuous veno-venous hemofiltration (CVVH) on early S-100B serum levels in septic shock patients, who were treated with either stress doses of hydrocortisone or placebo. METHODS: Twenty-four consecutive patients, who met the ACCP / SCCM criteria for septic shock, were enrolled in this prospective, randomised, double-blind, single-center trial. The severity of illness at recruitment was graded using the APACHE II and SAPS II scoring systems; the MODS was described by the SOFA score. All patients were prospectively randomised to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started in 12 patients with a loading dose of 100 mg and followed by a continuous infusion of 0.18 mg/kg/h for 6 days. RESULTS: Median S-100B serum levels of the hydrocortisone group decreased from 0.32 ng/ml (0.19-.60) at study entry to 0.07 ng/ml (0.04-0.32) 6 days later without significant differences compared to the placebo group. Patients undergoing CVVH showed significantly higher S-100B serum values compared to patients without CVVH (p>0.001). However, initial median S-100B serum levels of the CVVH group even increased from 0.92 ng/ml (0.16 - 4.63) to 2.33 ng/ml (0.59-2.44) 30 hours after study entry, reaching data ranges already known in patients with out-of-hospital cardiac arrest or severe traumatic brain injury. CONCLUSION: Early S-100B serum levels in septic shock patients receiving either stress doses of hydrocortisone or placebo were not influenced by CVVH. For the first time, we observed a similar extent of S-100B serum increase in CVVH patients, who had significantly higher S-100B serum values compared to those without CVVH, as reported for out-of-hospital cardiac arrest or severe traumatic brain injury. Hypercortisolemia induced by the infusion of stress doses of hydrocortisone did not significantly reduce early S-100B serum concentrations with time.

Adult↗

Corticosteroids for treating severe sepsis and septic shock.

BACKGROUND: Sepsis may be complicated by impaired corticosteroid production. Giving corticosteroids could potentially benefit patients. OBJECTIVES: To examine the effects of corticosteroids on death at one month in patients with severe sepsis and septic shock. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group's trial register (August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2003), MEDLINE (August 2003), EMBASE (August 2003), LILACS (August 2003), reference lists of articles, and also contacted trial authors. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials of corticosteroids versus placebo or supportive treatment in severe sepsis and septic shock. DATA COLLECTION AND ANALYSIS: Two pairs of reviewers agreed the eligibility of trials. One reviewer extracted data, which was checked by the other reviewers and the primary author of the paper whenever possible. We obtained some missing data from the trial authors. We assessed trial methodological quality. MAIN RESULTS: We identified 15 trials (n =2023). Corticosteroids did not change 28-day all-cause mortality (15 trials, n = 2022, relative risk (RR) 0.92, 95% confidence interval (CI) 0.75 to 1.14; random effects model) and hospital mortality (13 trials, n = 1418, RR 0.89, 95% CI 0.71 to 1.11; random effects model); however, there was statistically significant heterogeneity, with some evidence that this was related to the dosing strategy. Corticosteroids reduced intensive care unit mortality (4 trials, n = 425, RR 0.83, 95% CI 0.70 to 0.97), increased the proportion of shock reversal by day 7 (6 trials, n = 728, RR 1.22, 95% CI 1.06 to 1.40) and by day 28 (4 trials, n = 425, RR 1.26, 95% CI 1.04 to 1.52), without increasing the rate of gastroduodenal bleeding (10 trials, n = 1321, RR 1.16, 95% CI 0.82 to 1.65), superinfection (12 trials, n = 1705, RR 0.93, 95% CI 0.73 to 1.18), and of hyperglycaemia (6 trials, n = 608, RR 1.22, 0.84 to 1.78). REVIEWER'S CONCLUSIONS: Overall, corticosteroids did not change 28-day mortality and hospital mortality in severe sepsis and septic shock. Long course of low dose corticosteroids reduced 28-day all-cause mortality, and intensive care unit and hospital mortality.

Adrenal Cortex Hormones↗

Improved results after heart-lung transplantation: a 17-year experience.

OBJECTIVE: In selected patients with severe end-stage combined cardiopulmonary diseases, heart-lung transplantation (HLTx) remains the only therapeutical option for improving survival and quality of life. PATIENTS AND METHODS: Since 1983, 51 HLTx were done at our institution. Mean patient age was 27+/-12 years with a mean donor age of 25+/-11 years. Indications for HLTx were primary pulmonary hypertension (PPH) in 49% of patients, congenital heart disease in 39%, cystic fibrosis in 6%, and repeat-HLTx in 6%. Eleven patients were younger than 14 years. Among these pediatric patients, the indications were PPH in 55% of patients, pulmonary atresia with severe pulmonary artery hypoplasia in 27%, and cystic fibrosis and cardiomyopathy with fixed pulmonary hypertension in 9% of patients each. Two patients had additional liver transplantation because of chronic aggressive virus hepatitis. For organ preservation, Euro-Collins solution (lung perfusion) and cardioplegic solution according to Bretschneider (heart perfusion) were used until 1994. The University of Wisconsin solution replaced Bretschneider's solution in 1994. Since 1996, Perfadex, a low-potassium dextran-based preservation solution, replaced Euro-Collins. All transplantations were done through a median sternotomy until 1994. Thereafter, a transverse thoracotomy was used in patients with suspected adhesions. Until 1995, cyclosporine A, azathioprine, and prednisolone were used for immunosuppression. Since then, tacrolimus replaced cyclosporine A. RESULTS: From 1983 until 1993, perioperative mortality was 35% (6/19). From 1994 on perioperative mortality decreased to 12.5% (4/32). Early mortality was caused by graft failure (n=5), severe bleeding (n=2), multi-organ failure (n=2), and acute rejection (n=1). Cumulative survival rates were 81% after 30 days, 63% after 1 year, and 54% after 5 years, respectively. Since 1994, cumulative survival rates were markedly improved to 87% after 30 days, 81% after 6 months, and 78% after 1 year. There was no death during the first postoperative year among the 11 pediatric patients. Late death was mainly caused by obliterative bronchiolitis (OB; 76%); two patients died because of multi-organ failure or septic complications, respectively, and one patient died within the first postoperative year because of aspergillosis. CONCLUSION: Changes in organ preservation management, surgical techniques, and immunosuppressive therapy significantly improved the short- and mid-term results after HLTx. Long-term results can only be improved in cases of successful prevention and treatment of OB.

Adolescent↗

The serum cortisol:cortisone ratio in the postoperative acute-phase response.

OBJECTIVE: In a previous cross-sectional pilot investigation, an increase in the ratio of active cortisol to inactive cortisone in serum has been found as a general phenomenon during the acute-phase response. The aim of the present study was to further characterize this alteration of cortisol metabolism in patients undergoing elective cardiac bypass surgery. METHODS: Cortisol and cortisone were quantified by use of liquid-chromatography tandem mass spectrometry in sera that were sampled preoperatively and on the first 4 postoperative days (POD) from 16 patients undergoing aortocoronary bypass grafting (7.00 a.m.). RESULTS: The median serum cortisol concentration peaked on the first POD and then decreased statistically significantly until the end of the observation period: preoperatively, 245 nmol/l (IQR 198-331); 1st POD, 532 nmol/l (IQR 409-678 ); 4th POD, 373 nmol/l (IQR 306-493); p for trend = 0.019. In contrast, the cortisol:cortisone ratio was constantly increased approximately twofold on all POD compared to preoperative sampling: preoperatively, 5.4 (IQR 5.0-7.2); 1st POD, 11.3 (IQR 9.2-13.6); 4th POD, 9.9 (IQR 7.7-11.0), with no significant trend of normalization. CONCLUSION: Following major surgery, the substantial increase in the serum cortisol:cortisone ratio - reflecting a shift in the overall set-point of 11beta-hydroxysteroid dehydrogenase activity - is more sustained than the increase in serum cortisol; the increase in the cortisol:cortisone ratio seems to be a long-term phenomenon of the activation of the hypothalamic-pituitary-adrenocortical system by surgical stress and systemic inflammation.

Acute-Phase Reaction↗

Bronchial epithelial cell B7-1 and B7-2 mRNA expression after lung transplantation: a role in allograft rejection?

Obliterative bronchiolitis is commonly interpreted as chronic rejection and involves the bronchial and bronchiolar epithelium. Upregulation of major histocompatibility complex (MHC) II on bronchial epithelial cells (BEC) had been hypothesised to be an important trigger of a bronchus directed rejection response. More recently, the additional expression of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on antigen presenting cells were found to play an important role in the activation of T-lymphocytes in transplant rejection. The role of the expression of these molecules by BEC is unclear. BEC obtained by bronchial brushing and bronchoalveolar lavage fluid (BALF) cells from lung transplant recipients were studied and evaluated for messenger ribonucleic acid (mRNA) expression of B7-1 and B7-2 by semi-quantitative reverse transcriptase-polymerase chain reaction. Significantly elevated B7-1/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratios were found in BEC from patients examined during the first 3 months after lung transplantation. Interestingly, in a small group of patients with bronchiolitis obliterans syndrome the B7-1/GAPDH and B7-2/GAPDH ratios were significantly elevated for BEC, whereas no differences were found for the BALF cells. In summary, B7 messenger ribonucleic acid expression by bronchial epithelial cells may play a role in (chronic) lung allograft rejection.

Adult↗

The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder in survivors.

BACKGROUND: Exposure to intense physical and psychological stress during septic shock can result in posttraumatic stress disorder in survivors. Patients with chronic posttraumatic stress disorder often show sustained reductions in serum cortisol concentration. This investigation examines whether increasing serum cortisol levels with hydrocortisone treatment during septic shock reduces the incidence of posttraumatic stress disorder in survivors. METHODS: Patients (n = 20) were recruited from a prospective, randomized double-blind study on the hemodynamic effects of hydrocortisone during septic shock. Eleven patients had received placebo and nine stress doses of hydrocortisone. Posttraumatic stress disorder was diagnosed 31 months (median) after intensive care unit discharge using SCID-IV (DSM-IV-criteria). Furthermore, the number of categories of traumatic memory from ICU treatment was determined in both groups at that time. RESULTS: Only one of nine patients from the hydrocortisone group developed posttraumatic stress disorder, compared with seven of 11 patients in the placebo group (p =.02). There was no significant difference with regard to the number of categories of traumatic memory between the hydrocortisone and placebo groups. CONCLUSIONS: The administration of hydrocortisone during septic shock in a dosage similar to the endogenous maximal production rate was associated with a lower incidence of posttraumatic stress disorder in long-term survivors, which seems to be independent of the number of categories of traumatic memory.

Adult↗

[Exertion-related heat stroke. Lethal multiorgan failure from accidental hyperthermia in a 23 year old athlete].

We report the case of a 23-year-old rower who suffered from an exertional heatstroke while trying to lose 2 kg in weight by jogging before a competition. The development of this illness was favoured by clothes that were inappropriate for the environmental conditions and which the sportsman wore intentionally to enhance sweating. The maximum core temperature was over 43 degrees C. As a consequence the comatose patient developed a fulminant multi-organ failure with the liver ceasing its function, renal failure, massive rhabdomyolysis, and disseminated intravascular coagulation. In addition, he suffered from pericardial effusion and acute pulmonary failure (ARDS). In spite of maximum intensive care with an extensive substitution of blood products, continuous hemodiafiltration, and inhalative administration of nitrous oxide the young sportsman died 48 h after his admission to the intensive care unit. This tragic course demonstrates the danger of the widespread habit of losing weight by vigorously exercising with inappropriate clothes. In this article, potential risk factors, symptomatology, therapy, and methods of preventing an exertional heatstroke are shown and discussed.

Adult↗

Determination of serum cortisol by isotope-dilution liquid-chromatography electrospray ionization tandem mass spectrometry with on-line extraction.

A liquid chromatographic-mass spectrometric method for the determination of cortisol in serum using atmospheric pressure electrospray ionization and tandem mass spectrometry is described. During sample preparation, 150 microl of serum were deproteinized with methanol/zinc sulfate followed by on-line solid phase extraction employing column switching. Tri-deuterated cortisol was used as the internal standard. The following transitions were monitored: cortisol, 363>309 m/z; d3-cortisol, 366>312 m/z. The total run-time was 5 minutes. The method proved linear (0-500 microg/l; r=0.999), precise (total coefficient of variation between 5.0% and 3.2% at a mean cortisol concentration of 15.1 microg/l and 269 microg/l, respectively; n=16) and specific with regard to relevant endogenous and exogenous steroids.

Blood Chemical Analysis↗

Immunomodulation in septic shock: hydrocortisone differentially regulates cytokine responses.

Cortisol is known to be an immunomodulatory hormone that exerts suppressive and permissive effects on the immune response. Little is known regarding the evolution of the cytokine response in human septic shock in the presence of hypercortisolemia induced by infusion of stress doses of hydrocortisone. Twenty-four consecutive patients with high-out-put circulatory failure (cardiac index, >4 liters/min per m(2)) who met the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee criteria for septic shock were enrolled in a prospective, double-blind study. The severity of illness at the time of enrollment was graded using the Acute Physiology and Chronic Health Evaluation II system, and the evolution of sepsis-induced organ dysfunction syndrome was assessed using Sepsis-Related Organ Failure Assessment scores. After randomization, hyper-cortisolemia was induced in 12 patients by infusion of 100 mg of hydrocortisone, followed by continuous infusion of 0.18 mg/kg per h. Levels of the circulating cytokines tumor necrosis factor alpha (TNF), interleukin 6 (IL-6), IL-8, and IL-10 were serially measured at prospectively defined time points during the first 5 d after randomization. The infusion of hydrocortisone was associated with significant reductions in serum IL-6 and IL-8 levels and with earlier resolution of the sepsis-induced organ dysfunction syndrome. IL-6 levels started to differ between the groups on day 5. The TNF and IL-10 responses were not altered by hydrocortisone infusion. Hydrocortisone infusion in septic shock differentially regulated the cytokine responses. IL-6 and IL-8 levels decreased significantly and IL-6 levels differed between the groups, whereas TNF and IL-10 levels were not affected by hydrocortisone. Stress doses of hydrocortisone may be a valuable immunomodulatory therapy for septic shock.

Adjuvants, Immunologic↗

Elevated levels of interleukin-8 and transforming growth factor-beta in bronchoalveolar lavage fluid from patients with bronchiolitis obliterans syndrome: proinflammatory role of bronchial epithelial cells. Munich Lung Transplant Group.

BACKGROUND: Obliterative bronchiolitis (OB), the most important long-term complication after lung transplantation, is thought to be a manifestation of chronic rejection within the airways, with the hallmarks inflammation and fibroproliferation. METHODS: To characterize the inflammatory process in the context of OB we quantified tumor necrosis factor-alpha, interleukin (IL)-8, IL-10, and transforming growth factor (TGF)-beta on the protein and mRNA level in bronchoalveolar lavage fluid samples obtained from patients with bronchiolitis obliterans syndrome (BOS) and without BOS. In addition, bronchial cells sampled by bronchial brushing were analyzed for mRNA expression. RESULTS: In respiratory epithelial lining fluid (ELF) from BOS patients the protein levels of IL-8 (52.4+/-22.2 vs. 4.4+/-0.9 pg/ml ELF, P<0.005) and TGF-beta (5.6+/-1.9 vs. 0.9+/-0.2 ng/ml ELF, P<0.005) were significantly elevated. In addition, bronchoalveolar lavage fluid cells of BOS patients showed increased expression of TGF-beta (1.13+/-0.44 vs. 0.45+/-0.16, optical density [O.D.]/O.D. glyceraldehyde-3-phosphate dehydrogenase [GAPDH], P=0.11) and IL-8 (0.25+/-0.13 vs. 0.09+/-0.03 O.D/O.D. GAPDH, P=0.53) without the differences reaching statistical significance. In contrast, IL-8 mRNA expression of bronchial cells was significantly higher in the BOS group (0.85+/-0.40 vs. 0.22+/-0.10 O.D./O.D. GAPDH, P<0.05). CONCLUSIONS: We assume that IL-8 and TGF-beta may act as key mediators for airway inflammation and fibroproliferation in the pathogenesis of OB, with bronchial epithelial cells serving as a relevant source of IL-8.

Adult↗

[Cortisol in critically ill patients with sepsis: physiologic functions and therapeutic implications].

Modern immunology reveals that cortisol interacts with the immune response at virtually all levels exerting both suppressive and permissive effects. A pre-requisite for the defense against severe infections is the functional integrity of the hypothalamic-pituitary-adrenal axis (HPAA) resulting in adequate cortisol production. There is increasing evidence that cortisol physiology and regulation are substantially altered in the course of a septic shock. Patients with septic shock may suffer from relative adrenocortical insufficiency resulting in a relative deficiency of cortisol production. In addition, the number and the affinity of cellular glucocorticoid receptors are decreased by which cortisol action at cellular level is reduced. Since septic shock and adrenal insufficiency are sharing hemodynamic abnormalities such as hyperdynamic circulation and peripheral vasodilation, the administration of stress doses of hydrocortisone appears to be a rational therapeutic approach in patients with septic shock. Controlled studies have shown that stress doses of hydrocortisone attenuate the systemic inflammatory response. In two recent double-blind studies stress doses of hydrocortisone given in patients with septic shock have been demonstrated to reduce the time to shock reversal. The most important hemodynamic effect was an increase in systemic vascular resistance. Earlier weaning from vasopressor therapy was associated with a trend towards improvements in organ function and towards decreased mortality, respectively. Large-scale trials are on the way investigating the benefit of stress doses of hydrocortisone on the mortality of septic shock. The focus of this review are changes in glucocorticoid physiology and regulation during septic shock. Effects of stress doses of hydrocortisone on immune response and vascular tone in the course of a septic shock are being discussed.

Adrenal Insufficiency↗