Sheldon Magder

OBJECTIVES: To address the issues of Prevention and Management of Acute Renal Failure in the ICU Patient, using the format of an International Consensus Conference. METHODS AND QUESTIONS: Five main questions formulated by scientific advisors were addressed by experts during a 2-day symposium and a Jury summarized the available evidence: (1) Identification and definition of acute kidney insufficiency (AKI), this terminology being selected by the Jury; (2) Prevention of AKI during routine ICU Care; (3) Prevention in specific diseases, including liver failure, lung Injury, cardiac surgery, tumor lysis syndrome, rhabdomyolysis and elevated intraabdominal pressure; (4) Management of AKI, including nutrition, anticoagulation, and dialysate composition; (5) Impact of renal replacement therapy on mortality and recovery. RESULTS AND CONCLUSIONS: The Jury recommended the use of newly described definitions. AKI significantly contributes to the morbidity and mortality of critically ill patients, and adequate volume repletion is of major importance for its prevention, though correction of fluid deficit will not always prevent renal failure. Fluid resuscitation with crystalloids is effective and safe, and hyperoncotic solutions are not recommended because of their renal risk. Renal replacement therapy is a life-sustaining intervention that can provide a bridge to renal recovery; no method has proven to be superior, but careful management is essential for improving outcome.

OBJECTIVES: To measure stressed vascular volume in humans and to review the concepts of stressed and unstressed vascular volume. DESIGN: Observational study during surgical procedure. SETTING: Operating room at a university hospital. PATIENTS: Five patients undergoing hypothermic circulatory arrest for surgery on major vessels. INTERVENTION: We measured the volume that drained from the patient to the reservoir of the pump when the pump was turned off. MEASUREMENTS AND MAIN RESULTS: Stressed volume was 20.2+/-1.0 mL/kg, which is 30% of the predicted blood volume of these patients. CONCLUSION: The amount of blood volume that determines vascular filling pressure is only about a quarter of the total predicted volume, which means that there is a large reserve of unstressed volume that can be recruited to maintain vascular filling pressure.

Angiopoietin-1 (Ang-1), ligand for the endothelial cell-specific Tie-2 receptors, promotes migration and proliferation of endothelial cells, however, whether these effects are promoted through the release of a secondary mediator remains unclear. In this study, we assessed whether Ang-1 promotes endothelial cell migration and proliferation through the release of interleukin-8 (IL-8). Ang-1 elicited in human umbilical vein endothelial cells (HUVECs) a dose- and time-dependent increase in IL-8 production as a result of induction of mRNA and enhanced mRNA stability of IL-8 transcripts. IL-8 production is also elevated in HUVECs transduced with retroviruses expressing Ang-1. Neutralization of IL-8 in these cells with a specific antibody significantly attenuated proliferation and migration and induced caspase-3 activation. Exposure to Ang-1 triggered a significant increase in DNA binding of activator protein-1 (AP-1) to a relatively short fragment of IL-8 promoter. Upstream from the AP-1 complex, up-regulation of IL-8 transcription by Ang-1 was mediated through the Erk1/2, SAPK/JNK, and PI-3 kinase pathways, which triggered c-Jun phosphorylation on Ser63 and Ser73. These results suggest that promotion of endothelial migration and proliferation by Ang-1 is mediated, in part, through the production of IL-8, which acts in an autocrine fashion to suppress apoptosis and facilitate cell proliferation and migration.

OBJECTIVE: To determine the prevalence, hemodynamic characteristics, and risk factors for the low systemic vascular resistance (SVR) state in patients who have undergone cardiopulmonary bypass. DESIGN: Prospective cohort study. SETTING: The intensive care unit of a tertiary care hospital. PATIENTS: Seventy-nine consecutive patients who underwent coronary artery bypass graft, mitral valve, or aortic valve procedures. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Low SVR was defined as an indexed systemic vascular resistance (SVRi) of <1800 dyne x sec/cm5 x m2 at two consecutive times postoperatively. SVRi, cardiac index, mean arterial pressure, temperature, and central venous pressure were recorded before bypass and at 0, 1, 2, 4, 8, and 16 hrs after bypass. We recorded age, gender, urgency of operation, use of angiotensin-converting enzyme inhibitors and calcium channel blockers, ejection fraction, pump time, cross-clamp time, use of antifibrinolytics, type of oxygenator, amrinone use, postoperative biochemical and hematologic values, medication use, fluid balance, intensive care unit admission duration, and hospital admission duration. We assessed the role of diabetes mellitus, current smoking, and systemic hypertension. The incidence of the low-SVR state was 35 of 79 patients during a 3-month period (44%). At 8 hrs postoperatively, the SVRi in low-SVR and non-low-SVR patients was 1594+/-50 (SEM) and 2103+/-56 (SEM) dyne x sec/cm5 x m2, respectively (p < .001). In low-SVR patients, there was an initial and sustained increase in cardiac index and central venous pressure that preceded the decrease in mean arterial pressure. The decrease in mean arterial pressure was maximal at 8 hrs postoperatively. Patients with low SVR were more likely to have longer cross-clamp times, to be male, and to have lower postoperative platelet counts (p < .05 for all). Low-SVR patients were less likely to require dobutamine in the first 4 hrs postoperatively. CONCLUSIONS: Low SVR, a probable manifestation of systemic inflammatory response syndrome, is common in patients after cardiopulmonary bypass. These patients may respond better to a vasopressor to restore vascular tone than to volume loading to further increase cardiac index.