Glucocorticoid therapy for hypotension in the cardiac intensive care unit.

In recent years, it has been our practice to treat persistent hypotension in the cardiac intensive care unit with glucocorticoids. We undertook a retrospective review in an attempt to identify predictors of a hemodynamic response to steroids and of survival in these patients. Patients who had received glucocorticoids for hypotension over a 2-year period were identified retrospectively. Summary measures of blood pressure, heart rate, urine output, inotrope score, and volume of infused fluid were calculated for the 12 hours before and the 24 hours following initiation of glucocorticoid therapy. A hemodynamic response was defined as a > or =20% increase in mean blood pressure without an increase in inotrope score following initiation of steroid therapy. Fifty-one patients were included, of whom 6 (11.8%) died. Serum cortisol was measured in 43 patients (84.3%) and was below the lower limit of normal (<5 microg/dl) in 20 of these (46.5%). Following initiation of steroid therapy, blood pressure and urine output increased, whereas heart rate, inotrope score, and infused volume decreased. There were 21 (41.1%) hemodynamic responders, all of whom survived, whereas 6 of 30 (20%) nonresponders died (p = 0.036). No predictors of a hemodynamic response to steroid were identified. Some critically ill children with cardiac disease and inotrope refractory hypotension demonstrated hemodynamic improvement following glucocorticoid administration. An improvement in blood pressure following administration of glucocorticoid was associated with survival, but we were unable to identify predictors of that response.

Predictors of successful extubation in children.

Objective criteria to predict extubation outcome in mechanically ventilated children are not available. Our goal was to study factors associated with extubation success and to evaluate the usefulness of the rapid shallow breathing index (RSBI) and the compliance, resistance, oxygenation, and pressure index (CROP index) in children. Data were prospectively collected on 227 mechanically ventilated children. Patients successfully extubated had significantly better lung compliance (Cdyn: 0.59 +/- 0.91 versus 0.39 +/- 0.14 ml/kg/cm H(2)O), higher Pa(O(2))/FI(O(2)) ratio (382.4 +/- 181.2 versus 279.8 +/- 93.9), and lower Pa(CO(2)) (41.3 +/- 6.7 versus 47.3 +/- 8.5 mm Hg). Spontaneous breathing parameters showed significantly lower respiratory rates (RR) (36.6 +/- 17.9 versus 52.8 +/- 23 breaths/min), larger tidal volumes (VT) (7.3 +/- 2.6 versus 4.9 +/- 1.8 ml/kg), and greater muscle strength (negative inspiratory force [NIF]: 41.8 +/- 15.4 versus 35.1 +/- 12.5 cm H(2)O) in successfully extubated children. Extubation failures had higher RSBIs and lower CROP index values. A RSBI value of /= 0.15 ml/kg/breaths/min had a sensitivity of 83% and specificity of 53% for extubation success. Children failing extubation demonstrate abnormalities of respiratory function. The RSBI and CROP index are useful to predict pediatric extubation success.

Efficacy of peripherally inserted central venous catheters placed in noncentral veins.

BACKGROUND: Peripherally inserted central venous catheters (PICCs) are commonly used intravenous access devices in children. Although PICCs are intended to be placed in central veins, many fail to reach this location. These noncentral PICCs are used for administration of medications and isotonic solutions. OBJECTIVES: To examine the efficacy of noncentral PICCs for completion of therapy, the complications associated with their use, and the effectiveness of noncentral PICCs as compared with PICCs placed in a central vein. DESIGN: A prospective cohort study of children in whom PICCs were inserted, from January 1, 1994, to January 1, 1996. SETTING: A university-affiliated teaching institution. MAIN OUTCOME MEASUREMENT: Completion of intravenous therapy. RESULTS: A total of 587 PICCs were studied. Thirty-nine percent of PICCs were placed in noncentral veins. Centrally placed PICCs had significantly longer catheter duration compared with those placed noncentrally (16.6 vs 11.4 days, respectively). However, central and noncentral PICCs had similar therapy completion rates (73% and 69%, respectively). Catheter failure because of occlusion and accidental dislodgment were similar for central and noncentral PICCs. Likewise, complications caused by exit-site infection, phlebitis, and catheter-associated sepsis were also similar for catheters in the 2 locations. Catheter survival curves were similar for central and noncentral PICCs. CONCLUSIONS: Our study demonstrates that PICCs placed in noncentral veins provide reliable and safe intravenous access for administration of many medications and isotonic solutions for about 2 weeks' duration. The placement of PICCs in central veins may be restricted to those children who need central vascular access because of the type of intended therapy.

Cytoplasmic domain of E-selectin contains a non-tyrosine endocytosis signal.

E-selectin is an activation-dependent, endothelial cell-restricted adhesion molecule that is internalized and degraded rapidly once expressed on the cell surface. Tyrosine-containing structural motifs play an important role in the internalization of a number of integral proteins, and the membrane-proximal E-selectin cytoplasmic tyrosine residue (Tyr582) conforms to the endocytosis motif proposed previously. To determine the endocytosis motif in E-selectin, we selectively introduced truncation, substitution, and deletion mutations to the cytoplasmic tail of E-selectin. We analyzed the internalization kinetics of surface-expressed wild-type and mutant E-selectin constructs in transiently transfected Chinese hamster ovary cells using 125I-labeled E-selectin monoclonal antibody (125I-P6E2) in an acid elution assay. Interestingly, truncation immediately membrane proximal to Tyr582 (DeltaDGS construct) did not alter internalization kinetics significantly (DeltaDGS versus wild-type, mean surface half-life = 42 versus 45 min, respectively). Thus, it appears that the tyrosine residues are not required for internalization of E-selectin. Additional analyses indicated that Ser581 was necessary but alone was insufficient for surface E-selectin endocytosis. Thus, we conclude that there exists a novel non-tyrosine-containing endocytosis signal in the cytoplasmic tail which involves Ser581 and residues membrane-proximal to it.

The role of leukocyte and endothelial adhesion molecules in ischemia-reperfusion injury.

Reperfusion of ischemic tissue is associated with an acute inflammatory response that may further exacerbate vascular and tissue damage. Compelling evidence from a variety of animal models indicates that neutrophils are the principle effector cells of the reperfusion injury and that blockade of neutrophil adhesion to endothelium attenuates ischemia-reperfusion injury. "Anti-adhesion" therapy may represent a new approach to treatment of the many diverse clinical disorders in which ischemia-reperfusion occurs.

Survey of the use of peripherally inserted central venous catheters in children.

OBJECTIVE: Use of peripherally inserted central venous catheters (PICCs) to provide prolonged intravenous (IV) access in children is increasing. Our goal was to describe the children treated with PICCs in our institution, and to study catheter features such as catheter life, completion of therapy, and complications. Furthermore, we also evaluated PICC use in children completing therapy after discharge from our institution. METHODS: A prospective study of all PICCs inserted at the Children's Hospital and Medical Center (CHMC), a university-affiliated teaching institution, during a period of 18 months (January 1994 to July 1995). RESULTS: A total of 441 PICCs were inserted in 390 patients. Patient age ranged from 0 to 22 years with a mean of 5.4 +/- 6.0 years. No insertion complications occurred. Treatment of infectious disease (46%) was the most frequent reason for PICC insertion. All pediatric medical and surgical services used PICCs. Average catheter life was 13 +/- 12 days. Sixty-one percent of PICCs were used entirely at CHMC, while 39% were also used at home or at an outside hospital. Completion of therapy was achieved in 69% of PICCs. Among children who completed therapy outside our hospital, there was no difference in the rates of occlusion, accidental dislodgment, or infection. One hundred twenty-nine (29%) PICCs were removed for complications. Occlusion (7%), accidental displacement (8%), and suspicion of sepsis (8%) were the most common complications. Only 2% of PICCs had documented catheter-associated sepsis. CONCLUSIONS: PICCs provide reliable and safe access for prolonged IV therapy in neonates and children. The low incidence of complications with PICCs make them an attractive device for prolonged IV access. Similar complication rates with use in and out of hospital suggest that home IV therapy can be safely delivered with PICCs, avoiding expensive hospitalization.