Nobukazu Sato

Multicenter study verifying a method of noninvasive continuous cardiac output measurement using pulse wave transit time: a comparison with intermittent bolus thermodilution cardiac output.

BACKGROUND: Many technologies have been developed for minimally invasive monitoring of cardiac output. Estimated continuous cardiac output (esCCO) measurement using pulse wave transit time is one noninvasive method. Because it does not require any additional sensors other than those for conducting 3 basic forms of monitoring (electrocardiogram, pulse oximeter wave, and noninvasive (or invasive) arterial blood pressure measurement), esCCO measurement is potentially useful in routine clinical circulatory monitoring for any patient including low-risk patients. We evaluated the efficacy of noninvasive esCCO using pulse wave transit time in this multicenter study. METHODS: We compared esCCO and intermittent bolus thermodilution cardiac output (TDCO) in 213 patients, 139 intensive care units (ICUs), and 74 operating rooms (ORs), at 7 participating institutions. We performed electrocardiogram, pulse oximetry, TDCO, and arterial blood pressure measurements in patients in ICUs and ORs; a single calibration was performed to measure esCCO continuously. TDCO measurement was performed once daily for ICU patients and every hour for OR patients, and just before the removal of the pulmonary arterial catheter from patients in both the ICU and OR. We evaluated esCCO against TDCO with correlation analysis and Bland and Altman analysis and also assessed the change of bias over time. Furthermore, we inspected the impact of change in systemic vascular resistance (SVR) on change in bias because abnormal SVR was assumed to be a factor contributing to the change of the bias. RESULTS: From among 588 esCCO and TDCO datasets (excluding calibration points), 587 datasets were analyzed for 213 patients. The analysis results show a correlation coefficient of 0.79 (P < 0.0001, 95% confidence limits of 0.756–0.819), a bias (mean difference between esCCO and TDCO) of 0.13 L/min (95% confidence interval of bias 0.04–0.22 L/min), and a precision (1 SD) of 1.15 L/min (95% prediction interval was −2.13 to 2.39 L/min). There were no significant differences among 3 defined time intervals over 48 hours after calibration (repeated-measures analysis of variance P = 0.781) in the ICU. The influence of SVR on esCCO analysis showed a correlation coefficient between SVR and an error of 0.37 (P < 0.0001, 95% confidence interval 0.298–0.438). CONCLUSION: The efficacy of noninvasive esCCO technology was compared with TDCO in 213 cases. Five hundred eighty-seven datasets comparing esCCO and TDCO showed close correlation and small bias and precision, which were comparable to current arterial waveform analysis technologies.

The effects of argatroban on thrombin generation and hemostatic activation in vitro

We evaluated argatroban, a direct thrombin inhibitor, as a heparin adjunct for anticoagulation. Platelet-poor plasma (PPP) was isolated from blood collected from 12 volunteers. Thrombin generation measurements were performed in donor PPP that was mixed with antithrombin (AT)-poor plasma to yield AT levels of 0%, 20%, 60%, and 100%. Effects of argatroban (0–1.0 &mgr;g/mL), heparin (0.25 U/mL), or the combination of argatroban (0.5 &mgr;g/mL) and heparin were also studied. The addition of increasing concentrations of argatroban, heparin, or both to donor PPP (AT level ∼100%) caused progressive decreases in the lag time and peak formation of thrombin generation. Heparin (0.25 U/mL) at small AT concentrations had a minimal effect on lag time or peak thrombin formation; its effectiveness of inhibiting thrombin was directly correlated with the concentration of AT. Argatroban at 0.5 &mgr;g/mL was effective in decreasing thrombin formation at both low and normal AT levels, but it was most effective when combined with heparin. Additionally, blood samples were obtained from 47 cardiac surgical patients, and the interaction of heparin (>1.5 U/mL) and AT or argatroban on clot formation was evaluated with kaolin activated clotting times (ACTs). Significant increases of ACTs at all heparin levels were observed with the addition of argatroban (0.125 and 0.25 &mgr;g/mL). The addition of AT (0.2 U/mL) to heparinized blood samples further prolonged ACTs. In summary, we showed that argatroban, unlike heparin, could effectively reduce thrombin generation regardless of AT levels and could prolong ACTs in vitro at clinically used concentrations.

The In Vitro Reversal of Histamine-Induced Vasodilation in the Human Internal Mammary Artery

Anaphylactic shock therapy includes the use of catecholamines but they may not always be effective. Because vasodilation during anaphylaxis is a result of the endothelial release of multiple mediators, we investigated the effects of epinephrine, vasopressin, and inhibitors of nitric oxide and prostanoid pathways on histamine-induced relaxation in human internal mammary artery. The vessel segments were obtained intraoperatively and were suspended in organ chambers to record isometric tension. Norepinephrine (10−6 M) was used to precontract the rings followed by histamine (10−6.5 M) to relax the vessels and mimic vascular collapse. Epinephrine, vasopressin, methylene blue, NG-monomethyl-L-arginine (L-NMA) and indomethacin were added in a cumulative fashion to reverse the histamine-induced vasodilation. The internal mammary artery segments exhibited greater contraction in the presence of the epinephrine (4.9 ± 0.7g) compared with vasopressin (2.6 ± 0.7g). Vasopressin (10−11 to 10−7 M), methylene blue (10−7 to 10−5 M), L-NMA (10−6 to 10−4 M), and indomethacin (10−7 to 10−5 M) were only partially effective. These findings suggest that vasopressin and methylene blue may offer a potential therapeutic option in the treatment of histamine-induced vasodilatory shock.

The Vasodilatory Effects of Hydralazine, Nicardipine, Nitroglycerin, and Fenoldopam in the Human Umbilical Artery

We studied the effects of hydralazine, nicardipine, nitroglycerin, and fenoldopam (a dopamine D1-agonist) on isolated human umbilical arteries (HUA) from patients classified as normotensive and with pregnancy-induced hypertension (PIH). Umbilical artery rings were contracted with the thromboxane A2 analog (U46619; 10−8 M) and then exposed to cumulative concentrations of fenoldopam, hydralazine, nicardipine, and nitroglycerin. Second, rings were preexposed to prazosin (10−5 M), phenoxybenzamine (10−5 M), or none, and the constriction responses to increasing doses of fenoldopam or dopamine were recorded. Nitroglycerin, hydralazine, and nicardipine produced concentration-dependent relaxation of U46619-preconstricted HUA segments from normotensive and PIH patients. Fenoldopam and dopamine induced umbilical artery constriction in both normal and PIH rings at concentrations ≥10−5 M and ≥10−3 M, respectively. Phenoxybenzamine, but not prazosin, pretreatment irreversibly abolished fenoldopam-induced contraction. In this in vitro study, nitroglycerin was the most potent vasodilator of the HUA constricted with U46619, followed by nicardipine and hydralazine. However, fenoldopam constricted HUA rings only at supratherapeutic concentrations. No significant differences of vascular responses to fenoldopam (P = 0.3534), nitroglycerin (P = 0.7416), nicardipine (P = 0.0615), and hydralazine (P = 0.5514) between rings from normotensive or hypertensive pregnant patients were shown.

Blood component therapy guided by celite-activated thromboelastography for perioperative coagulopathy

Case 1 was a 54-year-old man (weight, 65kg; height, 160cm), who while a bicycling was involved in a head-on collision with a truck. He was brought to the emergency room with findings of a slightly depressed level of consciousness (Glasgow Coma Scale [GCS]II score of 4). His abdomen was distended, and computed tomography (CT) scanning revealed a highresolution lesion that was widespread throughout the mesentery, consistent with intraabdominal bleeding. He was orally intubated, and 1800ml of packed red blood cells (RBC) was administered in the emergency room. Subsequently, he was brought to the operating room for exploratory laparotomy. General anesthesia was maintained with O2 and sevoflurane. We were not able to detect any clot formation on celite-activated TEG immediately after induction of anesthesia (Fig. 1A). The patient showed continuous bleeding, which required crystalloid 5700ml; RBC 3600 ml; and fresh frozen plasma (FFP), 1200ml. Tranexamic acid 1500mg was given because increased fibrinolysis was also suspected from the minimal clot formation. Blood loss was estimated as 12000 ml by the time surgical hemostasis was established. Subsequent TEG showed near-normal reaction (R) time (8.3min), but severely decreased α angle and maximum amplitude (MA; 23° and 19mm), suggesting decreased platelet count (Fig. 1B). It also showed hyperfibrinolysis (Lysis index at 60min [LY60], 17.5%). Platelet count was measured together with the second TEG, and it was 23000/mm3, consistent with a reduced α angle and MA. Thirty-five units of platelets, FFP 560ml, and tranexamic acid 1000mg were given. At the end of the surgery, TEG showed near-normal values (Fig. 1C; R, 2.5min; α, 54°; MA, 47mm; and LY60, 5.5%). There was no increased bleeding from the drainage tube after the operation. Address correspondence to: J. Kawasaki Received: March 14, 2001 / Accepted: August 9, 2001