Jun Takezawa

Effects of norepinephrine on renal function in septic patients with normal and elevated serum lactate levels

Effects of iv norepinephrine (NE) on renal function were investigated retrospectively in 15 patients with hyperdynamic septic shock. All patients had either a low systolic BP less than 80 mm Hg, and/or oliguria less than 0.5 ml/kg-h. We examined their serum creatinine level (SCr), daily urine flow (UF), 24-h creatinine clearance (Ccr), and hemodynamic indices before and during NE infusion. Before NE administration, the patients were divided into those with with a serum lactate level (Lac) less than 20 mg/dl (group A, n = 9) and greater than 20 mg/dl (group B, n = 6). NE was infused continuously at rates between 0.05 and 0.24 microgram/kg.min which increased systolic BP by greater than or equal to 20 mm Hg. Cardiac index was not significantly changed in either group. In group A, NE increased both UF (p less than .05), and systemic vascular resistance index (SVRI) (p less than .01), but did not affect Ccr. In group B, NE did not increase UF nor SVRI, and decreased Ccr significantly (p less than .05). It is concluded that NE increased UF and SVRI only when Lac was in normal range; otherwise, NE reduced renal function. Thus, when administering NE to increase UF, both Lac and renal function should be monitored carefully.

Gabexate mesilate (FOY) therapy of disseminated intravascular coagulation due to sepsis.

Gabexate mesilate (FOY), a synthetic serine proteinase inhibitor, has an anticoagulant activity in the absence of antithrombin-III. We investigated FOY therapy for the treatment of disseminated intravascular coagulation (DIC) associated with sepsis in 15 patients (group F), and compared it with heparin therapy in 8 patients (group H). Successful treatment was observed in 13 patients in group F and in 4 patients in group H. The efficacy of the therapy in both groups was not significantly different. However, in patients whose antithrombin-III values were less than 20 mg/dl at the initiation of the therapy, FOY therapy was successful in 6 of 7 patients, whereas heparin therapy was not at all successful in 4 patients (p < 0.05). We conclude that FOY can be used as effectively as heparin for the treatment of DIC, and that FOY therapy is superior to heparin therapy in DIC associated with decreased antithrombin-III.

Circulatory responses to afterloading with phenylephrine in hyperdynamic sepsis.

We assessed cardiac function by acute pressure loading with phenylephrine in 7 patients who had hyperdynamic sepsis and in 8 patients who had heart disease. All patients with sepsis had a positive Limulus lysate test, a septic focus, and a cardiac output (CO) greater than 6.0 L/min. Phenylephrine was given iv to elevate systolic arterial pressure by 30 mm Hg. Cardiac index (CI) and stroke index (SI) increased significantly in patients with hyperdynamic sepsis, whereas systemic vascular resistance index (SVRI) showed no change. In patients with heart disease, CI and SI decreased significantly, whereas SVRI increased significantly. The marked differences in response to phenylephrine by the two groups suggest lack of cardiac dysfunction in patients with hyperdynamic sepsis.

Hyperlactemia can predict the prognosis of liver resection.

Although hyperlactemia is known to accompany hepatic failure and metabolic acidosis, few reports examined the relationships between lactate concentrations and outcome after liver resection. We examined the ability of arterial plasma lactate concentration to predict the patient outcome after hepatectomy. The relationships of arterial lactate and base excess (BE) measured on admission to the intensive care unit (ICU) after hepatectomy to postoperative outcome were investigated in 151 consecutive patients. Lactate level was significantly higher in nonsurvivors than in survivors (P < 0.001), and in patients with postoperative complications than in those without complications (P < 0.001). Base excess was significantly reduced in nonsurvivors (P < 0.001) and in patients with postoperative complications (P = 0.004). The area under the receiver-operator curve of lactate to mortality was 0.86, whereas that of BE to the mortality was 0.82. Moderate correlation was observed between the lactate level at ICU admission and the highest total bilirubin concentration measured within 14 days after the surgery (r = 0.61), whereas the correlation between BE and bilirubin levels was lower (r = 0.35). Using multivariate analysis, the lactate level independently predicted mortality (P = 0.008) and morbidity (P = 0.013). Lactate (P < 0.001) and BE (P = 0.0068) levels both independently predicted the highest bilirubin concentration. The arterial plasma lactate concentration measured on admission to ICU seemed an excellent predictor of patient outcome after liver resection.

Incidence and outcomes of ventilator-associated pneumonia in Japanese intensive care units: the Japanese nosocomial infection surveillance system.

OBJECTIVES To determine the incidence of ventilator-associated pneumonia (VAP) among intensive care unit (ICU) patients in Japan and to assess the impact of VAP on patient outcomes, including mortality, length of stay, and duration of mechanical ventilation. DESIGN Multicenter cohort study. SETTING Twenty-eight ICUs in multidisciplinary Japanese hospitals with more than 200 beds. PATIENTS A total of 21,909 patients 16 years or older who were admitted to an ICU between June 2002 and June 2004, stayed in the ICU for 24 to 1,000 hours, and were not transferred to another ICU. RESULTS The overall infection rates for nosocomial pneumonia and VAP were 6.5 cases per 1,000 patient-days and 12.6 cases per 1,000 ventilator-days, respectively. The standardized mortality rates for the patients with VAP was 1.3 (95% confidence interval [CI], 1.1-1.6): 1.1 (95% CI, 0.9-1.4) for the cases due to drug-susceptible pathogens and 1.5 (95% CI, 1.1-1.9) for the cases due to drug-resistant pathogens. After adjusting for Acute Physiology and Chronic Health Evaluation II score, the mean length of stay for the patients with VAP caused by drug-susceptible pathogens (15.2 days [95% CI, 14.6-15.8]) and by drug-resistant pathogens (17.8 days [95% CI, 17.0-18.6]) was significantly longer than that in the patients without nosocomial infection (6.8 days [95% CI, 6.7-6.9]). The mean duration of mechanical ventilation in the patients with VAP caused by drug-susceptible pathogens (12.0 days [95% CI, 11.5-12.5]) and drug-resistant pathogens (14.1 days [95% CI, 13.5-14.8]) was significantly longer than that in the patients without nosocomial infection (4.7 days [95% CI, 4.6-4.8]). CONCLUSION The incidence of VAP is substantial among ICU patients in Japan. The potential impact of VAP on patient outcomes emphasizes the importance of preventive measures against VAP, especially for VAP caused by drug-resistant pathogens.

Serial changes in cellular immunity of septic patients with multiple organ-system failure.

Total lymphocyte count, lymphocyte cell-surface markers (OKT3, OKT4, OKT8, and B-1), serum complement factors (C3 and C4), immunoglobulins (IgG, IgA, and IgM), ceruloplasmin (Crl), and transferrin (Trf) were determined weekly for nine septic postoperative patients, all of whom had multiple organ-system failure. The peripheral blood total lymphocyte count, its subpopulation, T-cell subset, and proliferative responses of lymphocyte to phytohemagglutinin (PHA) and concanavalin A (Con A) decreased in all patients. OKT3 and B-l decreased progressively in the four nonsurvivors compared with the five survivors. Although immunoglobulin levels were within the normal range in both groups, they tended to increase in survivors and decrease in nonsurvivors. Serial levels of C3, C4, Crl, and Trf increased in survivors but did not change in nonsurvivors. T-cell function and antibody-producing activity diminished progressively in nonsurvivors. These changes in cellular immunity may represent another manifestation of multiple organ-system failure during sepsis.

Low-dose intramuscular polymyxin B improves survival of septic rats.

UNLABELLED Polymyxin B (PLB) is a cationic antibiotic that also stoichiometrically neutralizes the lipid A moiety of endotoxin. We examined effects of a small dose of PLB on the mortality of rats with cecal ligation and puncture, on LPS-stimulated nitric oxide (NO) production, and on tumor necrosis factor alpha (TNF alpha) production by isolated rat Kupffer cells. MATERIALS AND METHODS In vivo studies: Cecal ligation and puncture (CLP) was performed under anesthesia in 28 rats. One hour after CLP, either 600 U/kg of PLB or saline was administered intramuscularly every 6 h (PLB group: n = 12; control group: n = 16). Plasma endotoxin was measured at 3 and 24 h after the CLP by the Endospecy test. This was compared with survival. IN VITRO STUDIES Kupffer cells were isolated from the normal rat liver. The cells were incubated with LPS or LPS + PLB. After 24 h, NO and TNF alpha content were measured using the Griess and ELISA methods, respectively. RESULTS Low dose PLB significantly decreased the endotoxin levels at both 3 and 24 h (5.5 +/- 2.1 pg/mL vs. 32.8 +/- 3.6 at 3 h; 26.1 +/- 6.1 vs. 49.1 +/- 5.6 at 24 h (p < .05) after CLP. PLB significantly improved survival of CLP rats (68.8% in the control group vs. 100% in the PLB treated group on 3 days after CLP, p < .001). PLB also attenuated NO and TNF alpha production from the Kupffer cells. CONCLUSION Intramuscular PLB administered in low doses may improve the mortality of sepsis.

Evaluation of a System for On-line Analysis of V̇O2 and V̇CO2 for Clinical Applicability

The authors evaluated the accuracy of a system to measure respiratory gas exchange on an on-line basis by comparing it with a gas collection method. The system incorporates a hot-wire flowmeter, a mass spectrometer, and a microcomputer. It performs on-line compensation for both transport delay and dynamic response of the mass spectrometer. Compensation of flow measurement for changing gas fractions also is performed. Excellent linear correlations were obtained between the two methods: 1) in animals during mechanical ventilation with room air (VO2:r = 0.995; VCO2:r = 0.993), and nitrous oxide in oxygen (VO2:r = 0.975; VCO2:r = 0.976); and 2) in men spontaneously breathing room air at different workloads (VO2:r = 0.999; VCO2:r = 0.998), and higher inspired oxygen fractions (FIO2 0.38 to 0.75) (VO2:r = 0.910; VCO2:r = 0.988). The authors consider that the system is suited for accurate and continuous measurement of respiratory gas exchange during mechanical ventilation, anesthesia, and exercise testing.

Alterations in Spectral Characteristics of Heart Rate Variability as a Correlate of Cardiac Autonomic Dysfunction after Esophagectomy or Pulmonary Resection

Background Both esophagectomy and pulmonary resection are associated with postoperative cardiac complications, partly because of autonomic perturbations involving the heart. This study was undertaken to determine whether heart rate variability (HRV), employed as an index of cardiac autonomic function, changes in patients undergoing esophagectomy or pulmonary resection. Methods Electrocardiographic RR intervals were measured in 20 esophagectomized patients, 10 undergoing right and 10 undergoing left pulmonary resection on the preoperative day as baseline data and on postoperative days 1, 3, 5, 7, 14, and 30. Instantaneous heart rate was calculated every 250 ms from 416-s data of RR intervals. Power spectra of HRV for 128 s were computed using a fast Fourier transform and normalized by squared mean heart rate. The averaged ten sets of normalized HRV power were obtained by integrating the following power spectral bands: the low-, (0.06-0.10 Hz), high- (0.15-0.40 Hz), and total-frequency regions (0.01-0.40 Hz). Results In the esophagectomy group, mean low-, high-, and total-frequency HRV power decreased after surgery to 17%, 6%, and 15% of their preoperative values, respectively, and these indexes remained suppressed for up to 30 days. After right pulmonary resection, low- and total-frequency HRV power decreased through 30 and 7 postoperative days, respectively. In the left pulmonary resection group, HRV remained unchanged. In the esophagectomy group, mean (+/-SEM) heart rate increased from 78 (+/-3) bpm to more than 90 bpm throughout the study, and body temperature from 36.5 (+/-0.1) degrees C to more than 37.0 degrees C through 14 postoperative days. Heart rate and body temperature remained increased for 3 days after pulmonary surgery. Mean arterial pressure remained unchanged in the three surgical groups. Conclusions Reductions in HRV after esophagectomy or right pulmonary resection indicate a substantial and prolonged surgical injury to the autonomic nervous control of pulse rate.

Amino acids and thiobarbituric acid reactive substances in cerebrospinal fluid and plasma of patients with septic encephalopathy.

Amino acids and thiobarbituric acid reactive substances (TBARs) in the cerebrospinal fluid (CSF) and plasma were identified and assayed in 5 patients with septic encephalopathy. Levels of all the high molecular weight neutral amino acids (LNAAs) appeared to increase in the CSF. CSF levels of phenylalanine (PHE) and methionine (MET) increased significantly by factors of 20.9 and 9.5, respectively, and the plasma PHE level increased 7.5-fold. No significant changes in branched-chain amino acids were observed in either the CSF or plasma. The CSF/plasma ratios of valine (VAL), tyrosine (TYR), PHE, and MET significantly increased to 0.21, 0.46, 0.52, and 0.52, respectively. TBAR levels increased 4-fold in the CSF and also were slightly increased in the plasma, suggesting that lipid peroxidation in the central nervous tissues is markedly increased. We conclude that increases in LNAA levels and in lipid peroxidation in the central nervous tissues may play important roles in the development of septic encephalopathy.