A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin

CONTEXT: The hypothalamic-pituitary-adrenal axis is a major determinant of the host response to stress. The relationship between its activation and patient outcome is not known. OBJECTIVE: To evaluate the prognostic value of cortisol levels and a short corticotropin stimulation test in patients with septic shock. DESIGN AND SETTING: Prospective inception cohort study conducted between October 1991 and September 1995 in 2 teaching hospital adult intensive care units in France. PARTICIPANTS: A total of 189 consecutive patients who met clinical criteria for septic shock. INTERVENTION: A short corticotropin stimulation test was performed in all patients by intravenously injecting 0.25 mg of tetracosactrin; blood samples were taken immediately before the test (T0) and 30 (T30) and 60 (T60) minutes afterward. MAIN OUTCOME MEASURES: Twenty-eight-day mortality as a function of variables collected at the onset of septic shock, including cortisol levels before the corticotropin test and the cortisol response to corticotropin (delta max, defined as the difference between T0 and the highest value between T30 and T60). RESULTS: The 28-day mortality was 58% (95% confidence interval [CI], 51%-65%) and median time to death was 17 days (95% CI, 14-27 days). In multivariate analysis, independent predictors of death (P < or = .001 for all) were McCabe score greater than 0, organ system failure score greater than 2, arterial lactate level greater than 2.8 mmol/L, ratio of PaO2 to fraction of inspired oxygen no more than 160 mm Hg, cortisol level at T0 greater than 34 microg/dL and delta max no more than 9 microg/dL. Three groups of patient prognoses were identified: good (cortisol level at T0 < or = 34 microg/dL and delta max > 9 microg/dL; 28-day mortality rate, 26%), intermediate (cortisol level at T0 34 microg/dL and delta max < or = 9 microg/dL or cortisol level at T0 > 34 microg/dL and delta max > 9 microg/dL; 28-day mortality rate, 67%), and poor (cortisol level at T0 > 34 microg/dL and delta max < or = 9 microg/dL; 28-day mortality rate, 82%). CONCLUSION: Our data suggest that a short corticotropin test has a good prognostic value and could be helpful in identifying patients with septic shock at high risk for death.     

Epidermal growth factor during pregnancy- a predictor of fetal growth retardation?]

Epidermal growth factor (EGF) in urine was measured at 4-week intervals in 83 women referred for suspected intrauterine growth retardation (IUGR); 138 women with normal singleton pregnancies and newborns of normal weight served as controls. Of the 83 women, 30 delivered babies with weight below the 10th percentile after week 37. During pregnancy these women had shown significantly lower EGF levels than women who delivered normal-weight babies. However, due to the wide distribution of individual EGF data, no clear clinical cut-off point between normal and IUGR values could be established.     

Effects of etomidate on free intracellular amino acid concentrations in polymorphonuclear leucocytes in vitro

BACKGROUND: Previous studies have shown the inhibitory effects of etomidate on polymorphonuclear leucocyte (PMN) function. No reports exist, however, regarding free intracellular amino acid metabolism, although physiological cell metabolism and basic cell functions rely upon a balanced intracellular amino acid content and the cell membrane-mediated separation of cellular amino acids from the extracellular plasma amino acid pool. Thus, in the current study, we evaluated the effects of etomidate on free intracellular amino acid metabolism in PMN. METHODS: With ethics committee approval, blood was withdrawn from 35 healthy volunteers and incubated (1 h) either with 0 microg/ml, 0.0156 microg/ml, 0.0625 microg/ml or 0.5 microg/ml of etomidate as well as with its additives (propylene glycol and Lipofundin MCT 10%). The PMN were separated using standardized Percoll-gradient and centrifugation procedure before deep-freezing and lyophilization techniques were employed. All PMN samples were dissolved in methanol/H2O, and the concentrations of free intracellular amino acids were monitored using both novel advanced PMN-separation and high-performance liquid chromatography techniques. RESULTS: Etomidate influenced important free amino acid profiles in PMN in a dose-dependent manner, indicating complex changes of cellular amino acid turnover. Neither propylene glycol nor Lipofundin MCT 10% changed free amino acid concentrations in PMN. CONCLUSIONS: For the first time, the effects of etomidate on free intracellular amino acid metabolism in PMN have been investigated. Our results draw attention to the biochemical pathways which may be involved in etomidate-induced alterations in PMN function and cellular immunocompetence.     

Idiopathic neuralgic amyotrophy in children. A distinct phenotype compared to the adult form

Two cases of neuralgic amyotrophy (idiopathic brachial plexus neuropathy) in children are presented and combined with a review of the literature. Difficulties in establishing the diagnosis are illustrated, and we give an overview of the phenotype of childhood neuralgic amyotrophy and its distinctions from the adult type. Pain, in adult cases present in over 95% of the cases, is less frequent in children, and its absence by no means excludes the diagnosis. In children under 8 weeks of age, the literature shows that a subsequent osteomyelitis of the shoulder or arm always seems to be involved, which warrants a close follow-up. Overall, recovery is less favourable in children, but when they fully recover they seem to do so in a shorter period of time than adults. We conclude that neuralgic amyotrophy in children is distinct from the adult variety, and that it has a definite place in the differential diagnosis of a sudden limp arm, even if it is painless.     

A clinical pathway to accelerate recovery after colonic resection

OBJECTIVE: To investigate the feasibility of a 48-hour postoperative stay program after colonic resection. SUMMARY BACKGROUND DATA: Postoperative hospital stay after colonic resection is usually 6 to 12 days, with a complication rate of 10% to 20%. Limiting factors for early recovery include stress-induced organ dysfunction, paralytic ileus, pain, and fatigue. It has been hypothesized that an accelerated multimodal rehabilitation program with optimal pain relief, stress reduction with regional anesthesia, early enteral nutrition, and early mobilization may enhance recovery and reduce the complication rate. METHODS: Sixty consecutive patients undergoing elective colonic resection were prospectively studied using a well-defined postoperative care program including continuous thoracic epidural analgesia and enforced early mobilization and enteral nutrition, and a planned 48-hour postoperative hospital stay. Postoperative follow-up was scheduled at 8 and 30 days. RESULTS: Median age was 74 years, with 20 patients in ASA group III-IV. Normal gastrointestinal function (defecation) occurred within 48 hours in 57 patients, and the median hospital stay was 2 days, with 32 patients staying 2 days after surgery. There were no cardiopulmonary complications. The readmission rate was 15%, including two patients with anastomotic dehiscence (one treated conservatively, one with colostomy); other readmissions required only short-term observation. CONCLUSION: A multimodal rehabilitation program may significantly reduce the postoperative hospital stay in high-risk patients undergoing colonic resection. Such a program may also reduce postoperative ileus and cardiopulmonary complications. These results may have important implications for the care of patients after colonic surgery and in the future assessment of open versus laparoscopic colonic resection.     

Non-invasive pulmonary aerosol delivery in mice by the endotracheal route.

In this report we present in detail a non-invasive pulmonary application method that can be a useful tool in studying drug and vaccine delivery to the lower airways. In this method the formulation is sprayed directly into the lungs of mice via the endotracheal route using a MicroSprayer aerolizer. Mean droplet size produced was 8 microm, appropriate for deposition in the large airways. Endotracheal application of suspension of fluorescent nanospheres, 200 nm in size, by this method resulted in nanoparticle deposition in the smaller airways (bronchi and bronchioles). Mice showed full recovery one day after administration of 50 microl of formulation. Furthermore, no mortality was observed as a result of the technique. We conclude that this endotracheal application is a useful tool for studying pulmonary drug delivery in mice. The technique is especially useful for the pulmonary application of vaccines, since it enables multiple administrations without a need for analgesics.     

Total soluble HLA class I and soluble HLA-G in multiple myeloma and monoclonal gammopathy of undetermined significance.

Serum beta2-microglobulin, the light chain of the HLA class I molecular complex, remains one of the best survival prognostic factors in multiple myeloma, but other HLA class I molecules might be of interest in monoclonal gammopathies. In this study, we evaluate total soluble HLA class I (HLA-Is) and soluble HLA-G (HLA-Gs) in 103 patients with newly diagnosed multiple myeloma, 30 patients with monoclonal gammopathy of undetermined significance (MGUS), and 30 healthy subjects, studying their prognostic value in multiple myeloma. In multiple myeloma patients, HLA-Is and HLA-Gs median values were 0.8 microg/mL and 28 ng/mL, respectively. Median HLA-Is concentration was higher in stage II and III multiple myeloma patients than in stage I multiple myeloma, MGUS, and control patients. Median HLA-Gs was significantly lower in healthy controls than in MGUS and multiple myeloma patients. A high level of HLA-Is (> or =2.1 microg/mL) was predictive of short survival (P = 0.017). For each given level of beta2-microglobulin, the relative risk of death was higher for patients with HLA-Is > or = 2.1 microg/mL than in patients with a lower level (P = 0.047). HLA-Gs, a marker of monoclonal gammopathy, was of no prognostic value, but the addition of HLA-Is to beta2-microglobulin produced an efficient prognostic score (P < 0.0001). HLA-Is is a new marker of multiple myeloma tumor load and provides additional survival prognostic information to beta2-microglobulin.