Corticosteroids in ARDS.
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Area Under Curve↗
Biomedical subjects
Reto Stocker
Publications and source records attributed to Reto Stocker.
Need for intracranial pressure monitoring following severe traumatic brain injury.
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Brain Injuries↗
Thiopental-induced apoptosis in lymphocytes is independent of CD95 activation.
BACKGROUND: Barbiturate coma is used in patients with traumatic brain injury whenever increases in intracranial pressure remain unresponsive to less aggressive therapeutic regimens. However, barbiturate-mediated neuroprotection correlates with lymphopenia, which increases the risk of infection. The mechanisms by which barbiturates lead to lymphopenia remain to be determined. METHODS: Freshly isolated human lymphocytes and Jurkat cells were incubated with the barbiturate thiopental for 24 and 48 h. Apoptosis was measured by fluorescein isothiocyanate-Annexin and propidium iodide staining, rhodamine 123 staining, and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method. Caspase-3 activity was detected by Western blot and substrate cleavage assay. RESULTS: Thiopental dose-dependently (5-500 microg/ml) increased apoptosis in Jurkat cells from basal levels (4.4 +/- 1.9%) to 29.7 +/- 2.8% after 24 h and 39.7 +/- 3.2% after 48 h, whereas in lymphocytes, thiopental-induced necrosis was observed. Parallel to apoptosis, thiopental dose-dependently increased caspase-3-like activity in Jurkat cells. However, the pan-caspase inhibitor z-VAD-fmk (20 microm) only marginally reduced thiopental-induced (250 microg/ml) apoptosis in Jurkat cells (20.2 +/- 2.5 to 17.2 +/- 2.5%) and necrosis in lymphocytes (39.2 +/- 7.5 to 30.7 +/- 14%). In contrast, anti-CD95-induced apoptosis in Jurkat cells (27.0 +/- 2.0%) was completely blocked by z-VAD-fmk (8.1 +/- 1.8%). Neither expression of CD95 on Jurkat cells nor pretreatment with a neutralizing anti-CD95 antibody influenced thiopental-induced apoptosis, indicating that thiopental induces apoptosis independently of the CD95 system. The nuclear factor kappaB inhibitor gliotoxin accelerated both thiopental- and CD95-mediated apoptosis, indicating a mutual control mechanism of thiopental- and CD95-induced apoptosis. CONCLUSIONS: Thiopental directly induces cell death in lymphocytes and Jurkat cells by a CD95-independent mechanism.
Apoptosis↗
Airway management and artificial ventilation in intensive care.
PURPOSE OF REVIEW: This article defines the indication for airway-securing measures and describes the actual state of knowledge about the available techniques. Various modes of ventilation and their rationale are presented. RECENT FINDINGS: New techniques in airway management and ventilation strategy are presented, explained and evaluated. SUMMARY: Respiratory failure is a major confounding factor of morbidity and mortality in critical care patients and contributes considerably to prolonged intensive-care unit stay. When respiratory impairment is acute, rapid assessment of essential respiratory functions such as airway patency, gas exchange, and cough function have the highest priority in patients in life-threatening conditions. Securing the airway is a basic and vital procedure that has to be applied either in an elective or an emergency situation. Various levels of difficulty in laryngoscopy, intubation and maintaining oxygenation can occur and require standardized protocols, an adequate level of expertise and appropriate equipment. In intubated patients as well as in patients without secured airway, ventilatory assistance of various degrees and invasivities may be required. In this article all clinically applied forms of ventilation, their advantages and disadvantages as well as the relevant settings are extensively presented and discussed.
Journal Article↗
The influence of two different hydroxyethyl starch solutions (6% HES 130/0.4 and 200/0.5) on blood viscosity.
We performed the current study to investigate the influence of 2 different hydroxyethyl starch (HES) solutions, the novel medium molecular weight HES 130/0.4 (6%) and HES 200/0.5 (6%), on plasma and whole blood viscosity in vitro and ex vivo in patients with severe head injury. For the in vitro experiments, blood was incubated with increasing concentrations (0%-50% vol/vol plasma) of either 6% HES 130/0.4 or 6% HES 200/0.5 solution. Plasma viscosity and whole blood viscosity (hematocrit [Hct] 45%) at high (94.5 s(-1)) and low (0.1 s(-1)) shear rates were determined. Both HES solutions increased plasma viscosity, but HES 130/0.4 to a lesser extent than HES 200/0.5. Whole blood viscosity was significantly less with HES 130/0.4 than with HES 200/0.5 at concentrations of 37.5% and larger. In the ex vivo study on 31 patients with severe cranio-cerebral trauma treated randomly with either HES 130/0.4 or HES 200/0.5 over several days, frozen plasma samples were thawed and plasma viscosity was determined. Blood was reconstituted with normal erythrocytes (0, Rh neg, Hct 45%) for whole blood viscosity measurements. In both groups plasma and blood viscosity tended to increase over time without statistical significance. Although the prominent effects found in vitro are not in keeping with the ex vivo data, they are likely to reflect the true clinical situation during repetitive, large-dose HES administration. We therefore conclude that HES 130/0.4 may have hemorheological advantages over conventional HES 200/0.5 when used in large quantities.
Blood Viscosity↗
Fluid resuscitation in the intensive care unit.
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Albumins↗
Ten years of lung transplantation in Switzerland: results of the Swiss Lung Transplant Registry.
OBJECTIVE: Lung transplantation has evolved from an experimental procedure to a viable therapeutic option in many countries. In Switzerland, the first lung transplant was performed in November 1992, more than ten years after the first successful procedure world-wide. Thenceforward, a prospective national lung transplant registry was established, principally to enable quality control. PATIENTS: The data of all patients transplanted in the two Swiss Lung Transplant centres Zurich University Hospital and Centre de Romandie (Geneva-Lausanne) were analysed. RESULTS: In 10 years 242 lung transplants have been performed. Underlying lung diseases were cystic fibrosis including bronchiectasis (32%), emphysema (32%), parenchymal disorders (19%), pulmonary hypertension (11%) and lymphangioleiomyomatosis (3%). There were only 3% redo procedures. The 1, 5 and 9 year survival rates were 77% (95% CI 72-82), 64% (95% CI 57-71) and 56% (95% CI 45-67), respectively. The 5 year survival rate of patients transplanted since 1998 was 72% (95% CI 64-80). Multivariate Cox regression analysis revealed that survival was significantly better in this group compared to those transplanted before 1998 (HR 0.44, 0.26-0.75). Patients aged 60 years and older (HR 5.67, 95% CI 2.50-12.89) and those with pulmonary hypertension (HR 2.01, 95% CI 1.10-3.65) had a significantly worse prognosis The most frequent causes of death were infections (29%), bronchiolitis obliterans syndrome (25%) and multiple organ failure (14%). CONCLUSION: The 10-year Swiss experience of lung transplantation compares favourably with the international data. The best results are obtained in cystic fibrosis, pulmonary emphysema and parenchymal disorders.
Adolescent↗
Increased expression of toll-like receptor-2 and -4 on leukocytes from patients with sepsis.
The reduced responsiveness of monocytes or granulocytes toward endotoxin (endotoxin tolerance) during sepsis may depend on Toll-like receptors (TLR). The expression of TLR-2 and TLR-4 was measured on neutrophils (PMN) and monocytes from patients with sepsis (n = 21) or healthy controls (n = 12). Leukocytes (1 x 10/mL) were incubated at 37 degrees C with or without a TLR-4 (LPS 1 microg/mL) or a TLR-2 ligand (MALP-2 2 nM). Surface expression of TLR-2 and TLR-4 at 0, 4, and 16 h was determined in FACS after staining with specific antibodies. The release of IL-8 and TNF-alpha was measured by ELISA. Freshly isolated PMN from patients with sepsis exhibited significantly (P < 0.05) higher mean fluorescence for TLR-2 (78.0 +/- 18.6) and TLR-4 (11.4 +/- 2.3) than controls (12.8 +/- 2.2 and 2.3 +/- 0.4). Similarly, monocytes from patients exhibited higher TLR-2 and TLR-4 expression (300.8 +/- 40.6 and 92.7 +/- 12.1) than cells from controls (149.5 +/- 27.1 and 52.2 +/- 7.6). In patients with sepsis, expression of TLR-2 and TLR-4 on PMN increased during 16 h of incubation (106.2 +/- 22.1 and 34.5 +/- 5.3), whereas it remained unchanged in controls (19.3 +/- 6.1 and 5.4 +/- 1.9). Incubation with LPS or MALP-2 had no effect on TLR-4 or TLR-2 expression in cells from either controls or patients. Despite increased TLR expression in cells from patients with sepsis, the endotoxin-induced release of TNF-alpha and IL-8 was indistinguishable from that in controls. Therefore, the endotoxin tolerance seen in patients with sepsis does not depend solely on TLR-2 or TLR-4 expression, and other mechanisms must be involved.
Adult↗
Stable creatinine clearance using large-dose HES versus reduced GFR.
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Creatinine↗
Mcl-1 correlates with reduced apoptosis in neutrophils from patients with sepsis.
BACKGROUND: Reduction of PMN apoptosis during sepsis contributes to the pathogenesis of multiple organ failure. Differential expression of Bcl-2 proteins, which participate in apoptosis regulation, may be responsible for the dysbalanced apoptosis seen in neutrophils from septic patients. In this study, expression of Mcl-1, Bid, Bcl-2, and Bax were investigated in septic neutrophils. STUDY DESIGN: PMN (1 x 10(6)/mL) from septic patients (n = 16) or healthy volunteers (n = 10) were incubated with either lipopolysaccharide (1 microg/mL), agonistic CD95 antibody (100 ng/mL), or medium for 16 hours. Apoptosis was quantified in FACS after propidium iodine staining. Mcl-1, Bid, Bcl-2, and Bax mRNA expression was detected by reverse transcriptase-polymerase chain reaction and protein determined by Western blot analysis. RESULTS: Spontaneous apoptosis was significantly reduced in PMN from septic patients (28.8% versus 64.0% in controls). Mcl-1 protein levels decreased in patients after 16 hours but remained stable in controls. Mcl-1 mRNA was found in freshly isolated PMN from controls and patients but remained elevated only in patients. Bid protein level decreased significantly in control PMN undergoing apoptosis but differences were less prominent in septic patients. Bid mRNA was detected only in freshly isolated PMN. No Bcl-2 mRNA or protein was detected in neutrophils from patients or controls, and detectable Bax protein and mRNA levels remained unchanged in all samples. CONCLUSIONS: Alterations of Bid and Mcl-1 protein in neutrophils may reflect the level of apoptosis. The upregulation of Mcl-1 mRNA in patients with sepsis suggests an active role for Mcl-1 in regulation of apoptosis during sepsis; Bax remains unchanged.
Adult↗
Successful use of the Molecular Adsorbent Recirculating System (MARS) in a patient with primary biliary cirrhosis (PBC) and treatment refractory pruritus.
Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease often associated with severe pruritus. Despite maximal medical management pruritus often persists and has a detrimental effect on quality of life. For patients that are refractory to all medical treatments, more invasive approaches have been tried. Recently, a new extracorporeal hemodiafiltration method, Molecular Adsorbent Recirculating System (MARS), has been described. Based on the hypothesis that hydrophobic, protein-bound metabolites play a major role in the development of liver failure, this device uses an albumin enriched dialysate to facilitate the removal of albumin bound toxins. AIM: To assess the safety and efficacy of a single MARS treatment on the pruritus score in a patient with PBC and treatment refractory pruritus. DESIGN/PATIENTS: A 61-year-old female patient with biopsy proven PBC, who had been accepted on our liver transplantation waiting list because of treatment refractory pruritus, was subjected to a single MARS treatment. RESULTS: At the end of a single 8 h MARS treatment session pruritus completely disappeared. Not unexpectedly, however, this effect was only short lived. Except for a slight hypercalcemia no adverse events were observed. CONCLUSION: A single MARS treatment very effectively improved pruritus. Long-term repetitive treatment, however, might be necessary to sustain its effectiveness.
Journal Article↗
Accuracy of automatic tube compensation in new-generation mechanical ventilators.
OBJECTIVE: To compare performance of flow-adapted compensation of endotracheal tube resistance (automatic tube compensation, ATC) between the original ATC system and ATC systems incorporated in commercially available ventilators. DESIGN: Bench study. SETTING: University research laboratory. SUBJECTS: The original ATC system, Dräger Evita 2 prototype, Dräger Evita 4, Puritan-Bennett 840. INTERVENTIONS: The four ventilators under investigation were alternatively connected via different sized endotracheal tubes and an artificial trachea to an active lung model. Test conditions consisted of two ventilatory modes (ATC vs. continuous positive airway pressure), three different sized endotracheal tubes (inner diameter 7.0, 8.0, and 9.0 mm), two ventilatory rates (15/min and 30/min), and four levels of positive end-expiratory pressure (0, 5, 10, and 15 cm H2O). MEASUREMENTS AND MAIN RESULTS: Performance of tube compensation was assessed by the amount of tube-related (additional) work of breathing (WOBadd), which was calculated on the basis of pressure gradient across the endotracheal tube. Compared with continuous positive airway pressure, ATC reduced inspiratory WOBadd by 58%, 68%, 50%, and 97% when using the Evita 4, the Evita 2 prototype, the Puritan-Bennett 840, and the original ATC system, respectively. Depending on endotracheal tube diameter and ventilatory pattern, inspiratory WOBadd was 0.12-5.2 J/L with the original ATC system, 1.5-28.9 J/L with the Puritan-Bennett 840, 10.4-21.0 J/L with the Evita 2 prototype, and 10.1-36.1 J/L with the Evita 4 (difference between each ventilator at identical test situations, p <.025). Expiratory WOBadd was reduced by 5%, 26%, 1%, and 70% with the Evita 4, the Evita 2 prototype, the Puritan-Bennett 840, and the original ATC system, respectively. The expiratory WOBadd caused by an endotracheal tube of 7.0 mm inner diameter was 5.5-42.2 J/L at a low ventilatory rate and 19.6-82.3 J/L at a high ventilatory rate. It was lowest with the original ATC system and highest with the Evita 4 ventilator (p <.025). CONCLUSIONS: Flow-adapted tube compensation by the original ATC system significantly reduced tube-related inspiratory and expiratory work of breathing. The commercially available ATC modes investigated here may be adequate for inspiratory but probably not for expiratory tube compensation.
Equipment Design↗
Repetitive large-dose infusion of the novel hydroxyethyl starch 130/0.4 in patients with severe head injury.
UNLABELLED: In this prospective, controlled, randomized, single-center study, we investigated the safety of repetitive large-dose infusion of a novel hydroxyethyl starch solution (6% HES 130/0.4) in cranio-cerebral trauma patients. Patients were randomized to receive either HES 130/0.4 (n = 16) at repetitive doses of up to 70 mL x kg(-1) x d(-1) (which is the largest HES dose reported in the literature) or the control HES 200/0.5 (n = 15) up to its approved dose limit of 33 mL x kg(-1) x d(-1) followed by human albumin up to a total dose (HES 200/0.5 + albumin) of 70 mL x kg(-1) x d(-1). We found no differences between groups in mortality, renal function, bleeding complications, and use of blood products. There were also no major differences in coagulation variables. However, at some time points, factor VIII, von Willebrand factor, and ristocetin cofactor were higher in the HES 130/0.4 group despite the large HES doses administered. We conclude that HES 130/0.4 can safely be used in critically ill head trauma patients over several days at doses of up to 70 mL x kg(-1) x d(-1). IMPLICATIONS: There are concerns that infusion of certain hydroxyethyl starch (HES) types for plasma volume expansion may influence coagulation and renal function. We investigated the safety of the novel HES 130/0.4 in patients with severe cranio-cerebral trauma. The repetitive HES doses administered in this study are the largest reported in the literature.
Adolescent↗
Long-term assessment of lung function in survivors of severe ARDS.
STUDY OBJECTIVES: To investigate the long-term outcome of lung function in survivors of severe ARDS after modern treatment strategies including lung protective mechanical ventilation and prone positioning maneuvers. DESIGN: Follow-up cohort study. SETTING: University hospital pulmonary division and level 1 trauma center. PATIENTS: Sixteen survivors of severe ARDS (from 1992 to 1994) with a lung injury score > or = 2.5. MEASUREMENTS: The follow-up study (from 1995 to 1996) included interview, physical examination, chest radiographs, static and dynamic lung volumes, diffusion capacity of the lung for carbon monoxide (DLCO), blood gas analysis, and cardiopulmonary exercise testing (CPET). RESULTS: The mean +/- SD interval between hospital discharge and functional assessment was 29.5 +/- 8.7 months (range, 15.0 to 40.7 months). In approximately one half of the patients, mild abnormalities in static and dynamic lung volumes were found. In 25% (4 of 16 patients), lung function was obstructive; in 25% (4 of 16 patients), lung function was restrictive; and in 6.3% (1 of 16 patients), a combined obstructive-restrictive pattern was revealed. DLCO was impaired in 12.5% (2 of 16 patients); gas exchange during exercise was impaired in 45.5% (5 of 11 patients). CONCLUSIONS: Residual obstructive and restrictive defects as well as impaired pulmonary gas exchange remain common after severe ARDS. CPET is a very sensitive measure to evaluate residual impairment of lung function after ARDS. Using CPET, reduced pulmonary gas exchange can be detected in many patients with normal DLCO.
Adult↗
Nontraumatic pancreatitis in spinal cord injury.
STUDY DESIGN: A retrospective analysis of 10 patients with pancreatitis after traumatic spinal cord injury. OBJECTIVES: To determine the conditions leading to nontraumatic pancreatitis in spinal cord injury. SUMMARY OF BACKGROUND DATA: Little is known in the literature about pancreatitis after spinal cord injury. A few authors suggest a multifactorial pathogenesis. METHODS: Over a 4-year period the case reports of 338 patients with traumatically caused SCI were reviewed concerning p-amylase and/or lipase elevations. Acute pancreatitis was defined as an elevation of p-amylase and/or lipase of more than three times the upper normal limit. RESULTS: Ten of 338 patients had p-amylase and/or lipase elevations three times higher than the upper normal limit. All 10 were male with a mean age of 40.4 years. The average onset time of acute pancreatitis was 16 +/- 5.5 days after trauma. The usual etiologic factors of acute pancreatitis such as obstructive, toxic, or traumatic events were excluded. CONCLUSION: The clinical recognition of acute pancreatitis in paraplegic and quadriplegic patients is hampered by diminished or lost visceral sensitivity and therefore is based on laboratory investigations. The current authors therefore hypothesize that acute pancreatitis in the setting of high-level spinal cord injury may result from a combination of locally mediated sphincter of Oddi dysfunction and vagal dominant innervation of the pancreatic gland in autonomic failure.
Adolescent↗
Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months.
MRC CRASH is a randomised controlled trial (ISRCTN74459797) of the effect of corticosteroids on death and disability after head injury. We randomly allocated 10,008 adults with head injury and a Glasgow Coma Scale score of 14 or less, within 8 h of injury, to a 48-h infusion of corticosteroid (methylprednisolone) or placebo. Data at 6 months were obtained for 9673 (96.7%) patients. The risk of death was higher in the corticosteroid group than in the placebo group (1248 [25.7%] vs 1075 [22.3%] deaths; relative risk 1.15, 95% CI 1.07-1.24; p=0.0001), as was the risk of death or severe disability (1828 [38.1%] vs 1728 [36.3%] dead or severely disabled; 1.05, 0.99-1.10; p=0.079). There was no evidence that the effect of corticosteroids differed by injury severity or time since injury. These results lend support to our earlier conclusion that corticosteroids should not be used routinely in the treatment of head injury.
Craniocerebral Trauma↗