Brian Krafte-Jacobs

Catheter-related thrombosis in critically ill children: Comparison of catheters with and without heparin bonding

OBJECTIVE To compare the incidence of and factors associated with vascular thrombosis after placement of heparin-bonded and standard femoral venous catheters. DESIGN Prospective, masked, clinical study. SETTING Multidisciplinary, tertiary, pediatric intensive care unit. PATIENTS Consecutive cases (n = 50) of critically ill children admitted to a pediatric intensive care unit in whom either a heparin-bonded (n = 25) or a standard (n = 25) femoral venous catheter was placed. MEASUREMENTS AND MAIN RESULTS Patients were examined by ultrasonography within 3 days of catheter insertion, weekly while the catheter was in place, and after catheter removal for evidence of vascular thrombosis. Data were collected prospectively regarding clinical evidence of catheter thrombosis, infusate composition, and positive blood culture results. Of 50 patients, 13 (26%) had thrombotic complications, 11 (44%) of the 25 patients in the standard-catheter group, in comparison with 2 (8%) of the 25 patients in the heparin-bonded catheter group (p = 0.004). In addition, there was a significantly higher incidence of positive blood culture results among patients in the standard-catheter group (24% vs 0%; p = 0.009). Positive catheter blood culture results were obtained in 38% of patients with thrombosis versus 3% without thrombosis (p = 0.001). Clinical evidence of thrombosis was found in 69% of patients with, versus 27% of patients without, ultrasound-proved thrombosis (p = 0.007). CONCLUSION Heparin bonding of catheters is associated with significantly fewer thrombotic complications. A reduced incidence of positive catheter-related blood culture results may be associated with the absence of thrombosis.

Circulating erythropoietin and interleukin-6 concentrations increase in critically ill children with sepsis and septic shock

ObjectivesTo investigate a possible relationship between plasma erythropoietin and interleukin-6 (IL-6) in critically ill children with sepsis or septic shock. To examine the modulatory effects of plasma from these patients on erythropoietin production in vitro, employing a cell culture system that uses the erythropoietin-producing Hep 3B cell line. DesignA prospective, controlled clinical and laboratory study. SettingA pediatric intensive care unit and research laboratory facility at a children’s hospital. PatientsChildren admitted to the pediatric intensive care unit with the diagnosis of sepsis or septic shock (n = 16), and control patients without infection or anemia (n = 16) were admitted to the study. InterventionsNone. Measurements and Main ResultsBlood samples were obtained from 16 children with sepsis or septic shock, and 16 age-matched controls. Plasma erythropoietin and IL-6 concentrations were measured using an enzyme-linked immunoassay. Plasma erythropoietin concentrations were significantly higher in children with sepsis or septic shock (120 ± 26 mIU/mL) than in controls (10 ± 2 mIU/mL) (p < .001). Plasma IL-6 concentrations were greater in children diagnosed with sepsis or septic shock (12,405 ± 6662 pg/mL) than in control patients (7 ± 1 pg/mL) (p < .001), and higher in septic shock patients (27,469 ± 13,647 pg/mL) than sepsis patients (688 ± 258 pg/mL) (p = .03). Hep 3B cells were incubated under hypoxic conditions in media containing plasma from control patients, or patients diagnosed with sepsis or septic shock. Media concentrations of erythropoietin were measured using an enzyme-linked immunoassay. Hep 3B cells incubated with plasma from patients diagnosed with sepsis or septic shock produced more erythropoietin (216 ± 23 mIU/mL) than Hep 3B cells incubated under the same conditions in media containing plasma from control patients (152 ± 11 mIU/mL) (p = .04). Hypoxic Hep 3B cell erythropoietin production in media incubated with plasma from patients diagnosed with sepsis or septic shock correlated significantly (although weakly) with plasma IL-6 values from these same patients (p = .03, r2 = .28). ConclusionsPlasma erythropoietin and IL-6 values are increased in critically ill children with sepsis or septic shock in comparison with controls. The data indicate that one or more plasma factors are responsible for stimulation of hypoxia-induced erythropoietin production in the Hep 3B cell line and suggest a possible role for IL-6 in the regulation of erythropoietin production in critically ill children with sepsis or septic shock. (Crit Care Med 1996; 24:1455–1459)

Increased circulating thrombomodulin in children with septic shock.

OBJECTIVES To test the hypothesis that children diagnosed with septic shock have increased plasma thrombomodulin values as a manifestation of microcirculatory dysfunction and endothelial injury; to determine whether plasma thrombomodulin concentrations are associated with the extent of multiple organ system failure and mortality. DESIGN Prospective, cohort study. SETTING Pediatric intensive care unit. PATIENTS Twenty-two children with septic shock and ten, healthy, control children. INTERVENTIONS Blood samples were obtained for plasma thrombomodulin determinations every 6 hrs for 72 hrs in septic shock patients and once in healthy control patients. MEASUREMENTS AND MAIN RESULTS Thirty-two children (22 septic shock, and 10 healthy controls) were enrolled in the study. Thrombomodulin concentrations were determined by an enzyme-linked immunosorbent assay. Septic shock nonsurvivors had significantly greater mean thrombomodulin concentrations (10.6 +/- 2.2 ng/mL) than septic shock survivors (5.5 +/- 0.6 ng/mL) (p < .05) and healthy control patients (3.4 +/- 0.2 ng/mL) (p < .01). Mean thrombomodulin values increased as the number of organ system failures increased. CONCLUSIONS Pediatric survivors and nonsurvivors of septic shock have circulating thrombomodulin concentrations 1.5 and 3 times greater than healthy control patients. These findings likely represent sepsis-induced endothelial injury. Patients with multiple organ system failure have circulating thrombomodulin concentrations which are associated with the extent of organ dysfunction. We speculate that measurement of plasma thrombomodulin concentrations in septic shock may be a useful indicator of the severity of endothelial damage and the development of multiple organ system failure.

Aerosolization of novel nitric oxide donors selectively reduce pulmonary hypertension

OBJECTIVES Inhaled nitric oxide (NO) reduces pulmonary hypertension in acute respiratory failure. Soluble nitric oxide donors (NO/nucleophile adducts-NONOates) are less cumbersome to deliver and may offer clinical advantage compared with inhaled NO. The objective of this study was to examine the pulmonary and systemic hemodynamic effects of tracheal aerosolization of a new class of NONOates in a porcine model of experimentally induced pulmonary hypertension. DESIGN Prospective, randomized, controlled study. SETTING Research laboratory. SUBJECTS Yorkshire pigs (n = 18), weighing 11.4 to 16.4 kg. INTERVENTIONS In anesthetized, mechanically ventilated, instrumented pigs, steady-state pulmonary hypertension (SSPH) was induced using a thromboxane agonist (U46619). Control animals received tracheal aerosolization of saline (n = 6); EP/NO animals received tracheal aerosolization of ethylputreanine NONOate (EP/ NO, n = 6); and DMAEP/NO animals received aerosolized 2-(dimethylamino) ethylputreanine NONOate (DMAEP/NO, n = 6). MEASUREMENTS AND MAIN RESULTS Mean pulmonary (MPAP) and mean systemic arterial pressures (MAP), atrial pressures, cardiac output, and arterial blood gases were measured following drug instillation. DMAEP/NO animals had significant reductions in pulmonary vascular resistance index (PVRI) and MPAP at all time points compared with SSPH and control animals (p < .05), while systemic vascular resistance index did not change. EP/NO animals had a significant reduction in PVRI and MPAP at some time points compared with SSPH and control animals. For both NONOate-treated animal groups, MAP and cardiac index did not change significantly compared with SSPH and control animals (p < .05). CONCLUSIONS In this porcine model of pulmonary hypertension, intratracheal aerosolization of soluble NO donors results in sustained reduction of pulmonary hypertension without reducing systemic arterial pressure. Intermittent aerosolization of NONOates may be an alternative to continuously inhaled NO in the treatment of acute pulmonary hypertension.