Chieko Mitaka

Two-dimensional echocardiographic evaluation of inferior vena cava, right ventricle, and left ventricle during positive-pressure ventilation with varying levels of positive end-expiratory pressure

The effects of intermittent positive-pressure ventilation (IPPV) with 0, 10, and 15 cm H2O of PEEP on inferior vena cava (IVC), right and left ventricular length and septal-lateral dimensions, and cardiac output were examined in 19 patients with respiratory failure using two-dimensional echocardiography. In five patients, cardiac output was also obtained by the thermodilution technique. As PEEP was increased, IVC dimensions increased during both inspiration and expiration, and the IVC collapsibility index decreased. This indicated an increase in venous stasis and decrease in venous return to the right atrium. Increasing PEEP was associated with progressive decreases in cardiac output, and length and septal-lateral dimensions of both ventricles. The decreased cardiac output during IPPV with 10 and 15 cm H2O PEEP may be due to the decreased venous return and ventricular filling. Cardiac output determined by echocardiography was correlated closely to that by the thermodilution technique.

Improvement of renal dysfunction in dogs with endotoxemia by a nonselective endothelin receptor antagonist

OBJECTIVES During endotoxemia, there is a marked and intractable decrease in systemic blood pressure, as well as profound vasoconstriction of the renal artery, thereby leading to septic shock and acute renal failure. The purpose of this study was to elucidate the effect of endothelin-1, a potent endothelium-derived vasoconstrictor peptide, on the hemodynamic and renal vascular changes seen in endotoxemia. DESIGN Prospective, comparative, experimental study. SETTING Laboratory at a university hospital. SUBJECTS Thirty-two male mongrel dogs (12.1+/-0.4 kg) under pentobarbital anesthesia. INTERVENTIONS Four groups of animals were studied: a) the lipopolysaccharide (LPS) group (n = 10), which received LPS (250 ng/kg/min for 2 hrs); b) the TAK-044 (a nonselective endothelinA/ endothelinB receptor antagonist) plus LPS group (n = 12), which received a bolus of TAK-044 (5 mg/kg) 0.5 hr before the start of LPS infusion; c) the TAK-044 plus vehicle group (n = 5), which received the same dose of TAK-044 0.5 hr before the start of vehicle infusion; and d) the control group (n = 5), which received only vehicle infusion. MEASUREMENTS AND MAIN RESULTS Changes in systemic and renal hemodynamics, blood gas, and renal function were measured at baseline, and at 0.5, 1, 2, 3, and 4 hrs. Infusion of LPS resulted in significant decreases in mean arterial pressure, arterial pH, Pao2, base excess, urine volume, renal blood flow, creatinine clearance, and urine osmolality. The administration of TAK-044 before LPS infusion did not affect the LPS-induced hypotension. In contrast, the receptor antagonist prevented LPS-induced metabolic acidosis and hypoxemia, and improved LPS-induced decreases in urine volume, renal blood flow, creatinine clearance, and urine osmolality, whereas TAK-044 or vehicle administered alone resulted in no significant hemodynamic or blood gas changes. Plasma endothelin-1 concentrations significantly increased after LPS infusion, with or without TAK-044. CONCLUSIONS The present study suggests that endothelin-1 plays an important role in the impaired renal hemodynamics and renal function associated with endotoxemia, and that endothelin receptor antagonists may be useful as therapeutic agents for acute renal failure during endotoxemia.

Relationships of circulating nitrite/nitrate levels to severity and multiple organ dysfunction syndrome in systemic inflammatory response syndrome

Excessive nitric oxide (NO) production has been implicated to be responsible for the development of septic shock. To determine whether plasma nitrite/nitrate (NOx) levels are related to the severity of systemic inflammatory response syndrome (SIRS) and the degree of multiple organ dysfunction, we studied plasma NOx levels in 70 patients with SIRS consisting of noninfectious SIRS (n = 32), sepsis (n = 23), and septic shock (n = 15). Infection is a microbial phenomenon characterized by an inflammatory response to the presence of microorganism. Positive culture for microorganism is regarded as infectious SIRS (sepsis and septic shock) and negative culture is regarded as noninfectious SIRS. Plasma samples collected from each patient within 24 h from admission to the intensive care unit were subjected for measurement of NOx levels, the stable end products of NO, by the high performance liquid chromatography-Greiss system. Mean plasma NOx levels in patients with SIRS were 52.8 ± 44 &mgr;M/L, ranging from 8.1 to 186.2 &mgr;M/L. Plasma NOx levels were positively correlated with Acute Physiology, Age, and Chronic Health Evaluation (APACHE) III score (r = 0.414, P < 0.01) and sequential organ failure assessment (SOFA) score (r = 0.433, P < 0.01). Plasma NOx levels in patients with sepsis (51.0 ± 38.5 &mgr;M/L) and septic shock (94.5 ± 53.7 &mgr;M/L) were significantly (P < 0.01) higher than those in patients with noninfectious SIRS (25.8 ± 16.9 &mgr;M/L) and healthy subjects (29.6 ± 8.9 &mgr;M/L). Our study shows that plasma NOx levels are increased in patients with infectious, but not noninfectious SIRS, which increase as the severity of SIRS and the development of multiple organ dysfunction syndrome, suggesting its possible pathogenic role in SIRS.

Endothelin-1 and atrial natriuretic peptide in septic shock

utes are being utilized. 4 Although a recent randomized trial of s tandard and high-dose epinephrine for cardiac arrest outside the hospital failed to reveal a survival advantage for the higher dose protocol, there was a t rend toward improved survival when high-dose epinephrine was administered within 10 minutes after the onset of cardiac arrest, as can be achieved in the catheterizat ion laboratory. 5 There are obvious l imitat ions to this report. I t is not randomized and it is retrospective. The dose of intracoronary epinephrine adminis tered to these pat ients was arbi t rar i ly selected and may not have resulted in the opt imal hemodynamic response. Int racoronary epinephrine was generally selected as a t rea tment of last resort and may have been more effective given earlier during the episode of hypotension. Fur thermore , it was often adminis tered simultaneously with other therapies, and its precise benefit, or even potent ia l harm to pat ients 5 through 8, is impossible to define. However, based on our observations in most pat ients of a rapid increase in arterial blood pressure after the adminis t ra t ion of intracoronary epinephrine, it would seem reasonable to consider its use in cases of refractory hypotension occurring during PTCA when other measures prove ineffective.

Increased Plasma Concentrations of Brain Natriuretic Peptide in Patients With Acute Lung Injury

PURPOSE This study was performed to elucidate the pathophysiological role of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in acute lung injury. MATERIALS AND METHODS We sequentially measured plasma concentrations of immunoreactive BNP and ANP in 10 patients (mean age, 63 years (with acute lung injury and compared those with hemodynamic parameters and pulmonary functions. RESULTS Plasma concentrations of immunoreactive BNP and ANP were markedly elevated at entry into the study. Plasma BNP concentrations during the early course (3 days) showed significant (P < .01) positive correlations with systemic vascular resistance index (r = .708) and pulmonary vascular resistance index (r = .573), but a negative correlation with cardiac index (r = .608). Plasma ANP concentrations showed a significant (P < .05) positive correlation with pulmonary capillary wedge pressure (r = .398). Plasma BNP in 4 patients who died and 1 patient with acute renal failure remained elevated during the entire hospital length of stay (12 days). CONCLUSION These findings suggest that circulating BNP plays an important role in acute lung injury along with ANP as a compensatory mechanism for cardiac dysfunction accompanied by increased systemic vascular resistance index and pulmonary vascular resistance index. Circulating BNP may be a sensitive humoral marker for the degree of ventricular dysfunction associated with acute lung injury.

Accuracy and repeatability of blood volume measurement by pulse dye densitometry compared to the conventional method using 51Cr-labeled red blood cells

AbstractObjective: To determine the accuracy and repeatability of pulse dye densitometry (PDD) in measuring blood volume (BV) by comparing it with the conventional method using 51Cr-labeled red blood cells (RI method) and by assessing sequential measurements. Design: Prospective clinical study. Setting: University hospital. Patientsandparticipants: Eleven adult ICU patients who received cardiac surgery (1st ICU day). Interventions: None. Measurementsandresults: After injecting indocyanine green (10 or 20 mg) into the right atrium, its arterial concentration was continuously monitored at the nose and finger by PDD, and BV was calculated by back extrapolating the logarithmic dye concentration on the dye elimination curve between 2.5 and 5.5 min after mean transit time to each mean transit time with the least squares method. These measurements were repeated in eight patients and performed only once in the other three, and the BV was measured concurrently by the RI method one time. The Bland-Altman method was used for evaluating differences between methods and within methods. The (percentage) biases and standard deviations between the PDD and RI methods and between the successive measurements by PDD at the finger and nose were 0.26±0.49 l (8.8±15.3%) and 0.004±0.25 l (0.06±5.9%) with the probe on a nostril, and 0.16±0.56 l (2.5±14.4%) and 0.19±0.31 l (4.7±7.3%) using the finger probe. The bias between methods was less than 10%, and the repeatability of PDD was better. Conclusions: As PDD can measure BV with good repeatability and with a small bias compared to the RI method, serial changes in BV can be evaluated at the bedside of critically ill patients noninvasively and repeatedly.

A longer duration of polymyxin B-immobilized fiber column hemoperfusion improves pulmonary oxygenation in patients with septic shock.

Endotoxin plays an important role in the pathogenesis of septic shock. Exposure of endothelial cells to endotoxin activates endothelial cells and increases the surface expression of adhesion molecules, markers of endothelial damage in organ dysfunction. Endotoxin adsorption therapy by polymyxin B-immobilized fiber column (PMX) hemoperfusion has been used for the treatment of septic shock patients. In this study, we measured plasma concentrations of endotoxin and soluble adhesion molecules in septic shock patients before and after the PMX treatment then observed on the relationships between actual duration of use and various outcomes. Sixteen patients with septic shock were studied. The 28-day mortality rate was 50%. The elevated plasma concentrations of endotoxin decreased after the PMX treatment in the survivors but not in the nonsurvivors. The norepinephrine dose and plasma concentrations of soluble endothelial leukocyte adhesion molecule 1 and soluble intercellular adhesion molecule 1 significantly (P < 0.05) decreased in the PMX greater-than-2-h (prolonged) group than in the PMX 2-h (conventional) group (−17.8 ± 14.6 vs. −1.8 ± 2.7 &mgr;g/min, −143.0 ± 111.0 vs. 0 ± 2.8 ng/mL, and −126.2 ± 144.9 vs. 16.5 ± 108.1 ng/mL, respectively). Changes in the PaO2-FiO2 ratio and the Sequential Organ Failure Assessment score were significantly (P < 0.05) more improved in the PMX greater-than-2-h group than in the PMX 2-h group (75.4 ± 80.7 vs. 1.2 ± 49.2 and −0.8 ± 1.8 vs. 2.2 ± 1.9 torr, respectively). We thus suggest that a longer duration of PMX treatment may improve the pulmonary oxygenation associated with decreased adhesion molecules in septic shock.

Polymyxin B-immobilized fiber column hemoperfusion therapy for septic shock.

Endotoxin, an outer membrane component of gram-negative bacteria, plays an important role in the pathogenesis of septic shock. Endotoxin adsorption therapy by polymyxin B-immobilized fiber column hemoperfusion (PMX) has been used for the treatment of septic shock patients in Japan since 1994. The covalent binding of polymyxin B onto the surface of the polystyrene-based carrier fiber in PMX inactivates the endotoxin in the blood without exerting toxicity. This study was performed as a systematic review to evaluate the efficacy and mechanism of PMX treatment in patients with septic shock. The PubMed database and references from identified articles were used to search and review the literature relating to the efficacy and mechanism of PMX treatment in patients with septic shock. Polymyxin B-immobilized fiber column hemoperfusion adsorbed monocytes, activated neutrophils, and anandamide, as well as endotoxin through direct covalent bond, hydrophobic and ionic interactions, and hydrodynamics, and reduced the blood concentrations of inflammatory cytokines, plasminogen activator inhibitor 1 and adhesion molecules. Polymyxin B-immobilized fiber column hemoperfusion increased blood pressure and reduced the dosage requirements for vasopressive/inotropic agents. The meta-analysis showed that PMX treatment had beneficial effects on the hemodynamics, pulmonary oxygenation, and mortality. These beneficial effects may be attributable to the direct adsorption of endotoxin, monocytes, activated neutrophils, and anandamide, as well as indirect decrease in inflammatory cytokines and other mediators. Polymyxin B-immobilized fiber column hemoperfusion treatment has additional effects on reducing endothelial damage, proapoptotic activity, and immunosuppression. Further studies will be needed to confirm the efficacy and mechanism of PMX treatment in septic shock.

PLASMA ALPHA -ATRIAL NATRIURETIC PEPTIDE CONCENTRATIONS IN ACUTE RESPIRATORY FAILURE ASSOCIATED WITH SEPSIS : PRELIMINARY STUDY

Plasma alpha-atrial natriuretic peptide (alpha-ANP) concentrations were measured during mechanical ventilation in nine patients with acute respiratory failure (ARF) associated with sepsis. The relationships between alpha-ANP and pulmonary hemodynamic variables were examined. A total of 22 measurements of alpha-ANP and other variables were obtained. The mean plasma alpha-ANP concentration of 22 measurements was 120.1 +/- 79.8 pg/ml (normal 31.7 +/- 12.0, mean +/- SD). Plasma alpha-ANP concentrations correlated with mean pulmonary artery pressure (MPAP) (r = .703, p less than .01) and pulmonary vascular resistance (PVR) (r = .606, p less than .01), but not with other variables. These findings suggest that alpha-ANP elevation may be related to the increases in MPAP and PVR in ARF associated with sepsis.

Cardiovascular and renal effects of carperitide and nesiritide in cardiovascular surgery patients: a systematic review and meta-analysis

IntroductionAcute kidney injury (AKI) following cardiovascular surgery is a common disease process and is associated with both morbidity and mortality. The aim of our study was to evaluate the cardiovascular and renal effects of an atrial natriuretic peptide (ANP, carperitide) and a B-type (or brain) natriuretic peptide (BNP, nesiritide) for preventing and treating AKI in cardiovascular surgery patients.MethodsElectronic databases, including PubMed, EMBASE and references from identified articles were used for a literature search.ResultsData on the infusion of ANP or BNP in cardiovascular surgery patients was collected from fifteen randomized controlled trials and combined. The infusion of ANP or BNP increased the urine output and creatinine clearance or glomerular filtration rate, and reduced the use of diuretics and the serum creatinine levels. A meta-analysis showed that ANP infusion significantly decreased peak serum creatinine levels, incidence of arrhythmia and renal replacement therapy. The meta-analysis also showed that ANP or BNP infusion significantly decreased the length of ICU stay and hospital stay compared with controls. However, the combined data were insufficient to determine how ANP or BNP infusion during the perioperative period influences long-term outcome in cardiovascular surgery patients.ConclusionsThe infusion of ANP or BNP may preserve postoperative renal function in cardiovascular surgery patients. A large, multicenter, prospective, randomized controlled trial will have to be performed to assess the therapeutic potential of ANP or BNP in preventing and treating AKI in the cardiovascular surgical setting.