Profile of Fluid Exposure and Recognition of Fluid Overload in Critically Ill Children.

OBJECTIVES: Fluid overload is common in the PICU and has been associated with increased morbidity and mortality. It remains unclear whether fluid overload is a surrogate marker for severity of illness and need for increased support, an iatrogenic modifiable risk factor, or a sign of oliguria. The proportions of various fluid intake contributing to fluid overload and its recognition have not been adequately examined. We aimed to: 1) describe the types and amounts of fluid exposure in the PICU and 2) identify the clinicians' recognition of fluid overload. SETTING: Noncardiac PICU in a quaternary care hospital. PATIENTS: Pediatric patients admitted for more than 24 hours. DESIGN: Prospective observational study over 28 days. INTERVENTIONS: Data were collected on the amount and type of fluid exposure-resuscitative boluses, blood products, enteral intake, parenteral nutrition (total parenteral nutrition), or modifiable fluids (IV fluids and medications) indexed to the patients' admission body surface area on days 1 and 3. Charts of patients admitted for 3 days who developed 15% fluid overload were reviewed to assess clinicians' recognition of fluid overload. MEASUREMENTS AND MAIN RESULTS: One hundred two patients were included. Day 1 median fluid exposure was 2,318 mL/m (1,831-3,037 mL/m; 1,646 mL/m [1,296-2,086 mL/m] modifiable fluids). Forty-seven patients (46%) received fluid boluses, and 16 (16%) received blood products. Day 3 median fluid exposure was 2,233 mL/m (1,904-2,556 mL/m; 750 mL/m [375-1,816 mL/m] modifiable fluids). Of the 54 patients, one patient (1.9%) received a fluid bolus and two (3.7%) received blood products. In our cohort, 47 of 54 (87%) had fluid exposure greater than 1,600 mL/m on day 3. Fluid overload was not recognized by the clinicians in 30% of the patients who developed more than 15% fluid overload. CONCLUSIONS: Although resuscitation fluids contributed more to fluid exposure on day 1 compared with day 3, fluid exposure frequently exceeded maintenance requirements on day 3. Fluid overload was not always recognized by PICU practitioners. Further studies to correlate modifiable fluid exposure to fluid overload and explore modifiable practice improvement opportunities are needed.

Prevalence and clinical demographics of cerebral salt wasting in patients with aneurysmal subarachnoid hemorrhage.

Hyponatremia is a frequent complication following subarachnoid hemorrhage (SAH), and is commonly attributed either to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting syndrome (CSW). The object of this study is to elucidate the clinical demographics and sequelae of hyponatremia due to CSW in subjects with aneurysmal SAH. Retrospective chart review of patients >18 years with aneurysmal SAH admitted between January 2004 and July 2007 was performed. Subjects with moderate to severe hyponatremia (serum sodium <130 mmol l(-1)) were divided into groups consistent with CSW and SIADH based on urine output, fluid balance, natriuresis, and response to saline infusion. Clinical demographics were compared. Of 316 subjects identified, hyponatremia (serum sodium <135 mmol l(-1)) was detected in 187 (59.2%) subjects and moderate to severe hyponatremia in 48 (15.2%). Of the latter group, 35.4% were categorized with SIADH and 22.9% with CSW. Compared to eunatremic subjects, hyponatremia was associated with significantly longer hospital stay (15.7 +/- 1.9 vs. 9.6 +/- 1.1 days, p < 0.001). Subjects with CSW had similar mortality and duration of hospital stay vs. those with SIADH. Though less common than SIADH, CSW was detected in approximately 23% of patients with history of aneurysmal SAH and was not clearly associated with enhanced morbidity and mortality compared to subjects with SIADH. Further studies regarding the pathogenesis and management, along with the medical consequences, of CSW are important.

The impact of hypopituitarism on function and performance in subjects with recent history of traumatic brain injury and aneurysmal subarachnoid haemorrhage.

PRIMARY OBJECTIVE: To correlate deficient pituitary function with life satisfaction and functional performance in subjects with a recent history of traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH). RESEARCH DESIGN: Cross-sectional study. METHODS AND PROCEDURES: Eighteen subjects with TBI and 16 subjects with SAH underwent pituitary hormonal and functional assessments 5-12 months following the event. Adrenal reserve was assessed with a 1 mcg cosyntropin stimulation test and growth hormone deficiency (GHD) was diagnosed by insufficient GH response to GHRH-Arginine stimulation. Assessments of life satisfaction and performance-function included the Satisfaction with Life Scale (SWLS), Craig Handicap Assessment and Reporting Technique (CHART) and the Mayo Portland Adaptability Inventory-4 (MPAI-4). RESULTS: Hypopituitarism was present in 20 (58.8%) subjects, including 50% with adrenal insufficiency. Hypothyroidism correlated with worse performance on SWLS and CHART measures. GHD was associated with poorer performance on CHART and MPAI-4 scale. CONCLUSIONS: In this series of subjects with history of TBI and SAH, hypothyroidism and GHD were associated with diminished life satisfaction and performance-function on multiple assessments. Further studies are necessary to determine the appropriate testing of adrenal reserve in this population and to determine the benefit of pituitary hormone replacement therapy on function following brain injury.

Stanniocalcin-1 inhibits thrombin-induced signaling and protects from bleomycin-induced lung injury.

Thrombin-induced and proteinase-activated receptor 1 (PAR1)-mediated signaling increases ROS production, activates ERK, and promotes inflammation and fibroblast proliferation in bleomycin-induced lung injury. Stanniocalcin-1 (STC1) activates anti-oxidant pathways, inhibits inflammation and provides cytoprotection; hence, we hypothesized that STC1 will inhibit thrombin/PAR1 signaling and protect from bleomycin-induced pneumonitis. We determined thrombin level and activity, thrombin-induced PAR-1-mediated signaling, superoxide generation and lung pathology after intra-tracheal administration of bleomycin to WT and STC1 Tg mice. Lungs of bleomycin-treated WT mice display: severe pneumonitis; increased generation of superoxide; vascular leak; increased thrombin protein abundance and activity; activation of ERK; greater cytokine/chemokine release and infiltration with T-cells and macrophages. Lungs of STC1 Tg mice displayed none of the above changes. Mechanistic analysis in cultured pulmonary epithelial cells (A549) suggests that STC1 inhibits thrombin-induced and PAR1-mediated ERK activation through suppression of superoxide. In conclusion, STC1 blunts bleomycin-induced rise in thrombin protein and activity, diminishes thrombin-induced signaling through PAR1 to ERK, and inhibits bleomycin-induced pneumonitis. Moreover, our study identifies a new set of cytokines/chemokines, which play a role in the pathogenesis of bleomycin-induced lung injury. These findings broaden the array of potential therapeutic targets for the treatment of lung diseases characterized by thrombin activation, oxidant stress and inflammation.