Adrenocorticotropic hormone and cortisol response to corticotropin releasing hormone in the critically ill—a novel assessment of the hypothalamic-pituitary-adrenal axis

The pathophysiology of adrenal insufficiency, common in surgical intensive care units, has not been fully elucidated. Patients at risk (age > 55 years, in the surgical intensive care unit >1 week, baseline cortisol < 20 μg/dL) were enrolled. After measuring cortisol and adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH) was administered. ACTH and cortisol were measured over 120 minutes. Short and long cosyntropin stimulation tests determined adrenal function. Area under the curve (AUC) and mixed linear models were used to compare cortisol and ACTH responses. Patients were grouped according to survival and response to stimulation testing. Chi-square and t tests were performed, and P values < .05 were considered statistically significant. Six of 25 patients responded poorly to cosyntropin, and 5 died compared with 3 after a normal response ( P < .01). ACTH (AUC) and ACTH peak were increased in nonsurvivors after CRH administration. Cortisol peak and AUC were not different. ACTH responsiveness was increased in nonsurvivors and may predict mortality

Bioavailability of oral fluconazole in critically ill abdominal trauma patients with and without abdominal wall closure: a randomized crossover clinical trial

Patients with non-apposed fascial edges, known as laparostomy patients, have traditionally been given intravenous medications, because enteral absorption of medications was thought to be unpredictable. We hypothesized that critically ill patients with "open abdomens" would have bioavailability similar to that of matched patients with closed fascial edges. Fluconazole, a commonly prescribed anti-fungal with good bioavailability was used as a marker of absorption. Postoperative abdominal trauma patients were enrolled in a case-control (laparostomy versus closed abdomen) crossover design study to receive either an oral or parenteral fluconazole (400 mg loading dose followed by 200 mg QD) for one week. After a washout period, the alternate route of administration was used for the second week. Blood levels were collected at the end of each week of therapy. Rectal swab stool specimens were cultured for fungi on days 0, 7, and 15. Sixteen patients were studied. The mean injury severity score was 23 (range 9-41). The bioavailability of enteral fluconazole was 51% +/- 30% in the open abdomen and 63% +/- 19% (p = 0.347) in the closed abdomen patients. There was great variation in the bioavailability between the individual patients, with a range of 30%-100% in both groups. Three patients developed rectal colonization with Candida krusei. The bioavailability of enterally dosed fluconazole was highly variable in both the open and closed abdomen patients. Intravenous administration of pharmaceuticals may provide more reliable serum levels in the first 2 weeks after trauma-related laparotomy

RNA target profiles direct the discovery of virulence functions for the cold-shock proteins CspC and CspE.

The functions of many bacterial RNA-binding proteins remain obscure because of a lack of knowledge of their cellular ligands. Although well-studied cold-shock protein A (CspA) family members are induced and function at low temperature, others are highly expressed in infection-relevant conditions. Here, we have profiled transcripts bound in vivo by the CspA family members of Salmonella enterica serovar Typhimurium to link the constitutively expressed CspC and CspE proteins with virulence pathways. Phenotypic assays in vitro demonstrated a crucial role for these proteins in membrane stress, motility, and biofilm formation. Moreover, double deletion of cspC and cspE fully attenuates Salmonella in systemic mouse infection. In other words, the RNA ligand-centric approach taken here overcomes a problematic molecular redundancy of CspC and CspE that likely explains why these proteins have evaded selection in previous virulence factor screens in animals. Our results highlight RNA-binding proteins as regulators of pathogenicity and potential targets of antimicrobial therapy. They also suggest that globally acting RNA-binding proteins are more common in bacteria than currently appreciated

Inter- and intrarater reliability in computed axial tomographic grading of splenic injury: why so many grading scales?

After splenic trauma, critical decisions regarding operative intervention are often made with the aid of computed axial tomographic (CT) scan findings. No CT scan-based grading scale has been demonstrated to predict accurately which patients require operative or radiologic intervention for their splenic injuries. We hypothesized that use of the most common grading scale, the American Association for the Surgery of Trauma scale, would be associated with low intra- and interreliability scores. We assessed the ability of experienced trauma radiologists to differentiate grade III from grade IV splenic injuries. The films of patients who had undergone abdominal CT scanning before splenectomy for grade III or IV injuries were serially evaluated by four trauma radiology faculty weekly for 3 weeks. We assessed intra- and interrater reliability for grading and for presence of contrast blush. Intrarater reproducibility yielded a weighted kappa score of 0.15 to 0.77. Interrater reliability weighted kappa scores ranged from 0 to 0.84, with a mean value of 0.23. CT imaging is not reliable for identifying grades III and IV splenic injury, as experienced radiologists often underestimate the magnitude of injury. Interrater reliability is poor. Factors other than the CT grade of splenic injury should determine whether patients require operative or angiographic therapy

Splanchnic Hypoperfusion-Directed Therapies in Trauma: A Prospective, Randomized Trial

Splanchnic hypoperfusion as reflected by gastric intramucosal acidosis has been recognized as an important determinant of outcome in shock. A comprehensive splanchnic hypoperfusion-ischemia reperfusion (IRP) protocol was evaluated against conventional shock management protocols in critical trauma patients. The study was a prospective randomized trial comparing three therapeutic approaches to hypoperfusion after severe trauma in 151 trauma patients admitted to the intensive care unit. Group 1 patients received hemodynamic support based on conventional indicators of hypoperfusion. In group 2, resuscitation was further guided by gastric tonometry-derived estimates of splanchnic hypoperfusion and included more invasive hemodynamic monitoring and additional administration of colloid or crystalloid solutions, or inotropic support. Group 3 patients additionally received therapies specifically aimed at optimizing splanchnic perfusion and minimizing oxidant-mediated damage from reperfusion. The three groups were similar based on age, Injury Severity Score, and Acute Physiology and Chronic Health Evaluation II Scores. There were no statistically significant differences in mortality rates, organ dysfunction, ventilator days, or length of stay between any of the interventions. Techniques of optimization of splanchnic perfusion and minimization of oxidant-mediated reperfusion injury evaluated in this study were not advantageous relative to standard resuscitation measures guided by conventional or tonometric measures of hypoperfusion in the therapy of occult and clinical shock in trauma patients