Toshihisa Nosaka

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.

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.

Nourishment of hepatocellular carcinoma cells through the portal blood flow with and without transcatheter arterial embolization

Background. Although transcatheter arterial embolization (TAE) for hepatocellular carcinoma (HCC) is very effective, local recurrence is not so rare. The reason is thought to be related to portal blood flow. The changes in the nourishing vessels in HCC after TAE were examined from the viewpoint of cell kinetics with direct reference to intracellular transportation of biochemical substrates, namely 5 bromo‐2′‐deoxyuridine (BrdU), an analogue of thymidine.

An increase in urinary nitrite/nitrate excretion is associated with the hyperdynamic state after cardiovascular surgery

Objectives. To test the hypotheses (1) that nitric oxide (NO) production is stimulated after cardiovascular surgery and is related to the hyperdynamic state and (2) that NO production is more prominent in patients with cardiopulmonary bypass.Design: Prospective, clinical study.Setting: Intensive care unit in a university hospital.Patients: One hundred patients after cardiovascular surgery: coronary artery bypass graft with (n=53) and without (n=17) cardiopulmonary bypass, valve surgery with cardiopulmonary bypass (n=23) and thoracic aortic replacement with cardiopulmonary bypass (n=7).Interventions: None.Measurements and results: Urinary nitrite/nitrate (NOx) excretion was measured by the high-performance liquid chromatography-Griess system as an index of endogenous NO production during the first 2 postoperative days. Hemodynamic variables, hematologic variables and serum C-reactive protein concentrations were measured after the operation. Urinary NOx concentrations were 146+/–70 and 190+/–93 µmol/l, and the amounts of NOx excreted in the urine were 23+/–10 and 18+/–8 µmol/h on the 1st and 2nd days, respectively. Urinary NOx excretions were positively correlated with the cardiac index (P<0.01), but inversely correlated with the systemic vascular resistance index (P<0.01). Urinary NOx concentrations were positively correlated with serum C-reactive protein concentrations (P<0.01), but inversely correlated with the cardiopulmonary bypass time (P<0.01). The urinary NOx concentration was highest in patients undergoing coronary artery bypass graft without cardiopulmonary bypass.Conclusion: These findings suggest, firstly, that NO production is stimulated by a surgical inflammatory response and, secondly, that the endogenous NO contributes to the increase in cardiac output that accompanies the reduced systemic vascular resistance after cardiovascular surgery.

Continuous monitoring of gastric intraluminal carbon dioxide pressure, cardiac output, and end-tidal carbon dioxide pressure in the perioperative period in patients receiving cardiovascular surgery using cardiopulmonary bypass

Objective To verify the hypothesis that the gastric intraluminal Pco2 (Pgco2) changes independently of the change in cardiac output (CO) during and after cardiovascular surgery using cardiopulmonary bypass (CPB), and that the elevation of Pgco2 affects the patients’ morbidity. Design Prospective, noninterventional study. Setting Medical/surgical intensive care unit and operating theater of a university hospital. Patients Sixteen adults patients receiving elective cardiovascular surgery using CPB. Interventions None. Measurements and Main Results After induction of anesthesia, the patients were fitted with a gastric tube equipped at the tip with a CO2 sensor (ion-selective field effect transistor) that can continuously measure real-time Pgco2, and a pulmonary artery catheter capable of monitoring continuous CO (CCO) and end-tidal CO2. Data from the devices was uploaded to a personal computer every 2 mins until the catheter was pulled off based on clinical judgment (Pgco2 values were blinded to everyone except the investigator). One patient expired as a result of multiple organ failure subsequent to sepsis, and postoperative morbidity assessed by the peak SOFA (sequential organ failure assessment) score (mean ± sd 6.9 ± 3.5; range, 2–13) was correlated with the peak Pgco2 during intensive care unit stay (mean ± sd 74.1 ± 30.7 mm Hg; range, 45–169 mm Hg) (p < .01, by regression analysis). The peak Pgco2 during surgery (mean ± sd 71.1 ± 18.1 mm Hg; range, 44–115 mm Hg) had no correlation with the postoperative morbidity. From analysis of CCO before, during, and after returning from the above 60 mm Hg of Pgco2, Pgco2 changed independently of CCO. Conclusions Pgco2 changed independently of CCO, and its postoperative elevation was related to morbidity, even in the group of patients with a good outcome. Continuous monitoring of Pgco2 is useful for the detection of morbidity and can be expected to help elucidate the pathophysiology of change of Pgco2.

Varicose bleeding after liver transplantation in a patient with severe portosystemic shunts.

Recipients for liver transplantation often have portosystemic shunts due to portal hypertension. It is an important problem whether such shunts should be ligated during operations. Ligating the shunts seems of benefit for increasing portal blood flow to the liver, but it is sometimes difficult technically, and it is invasive to the patient. We experienced a recipient with huge portosystemic shunts and no esophageal varices before living-related liver transplantation. Some shunts were ligated during operation to increase portal blood flow to the graft. Unfortunately, the patient suffered severe bleeding from esophagogastric varices after he underwent retransplantation owing to accidental liver failure. Based on our experience, extreme care should be exercised to avoid varicose bleeding after ligating the portosystemic shunts of liver transplantation patients.