Extravascular lung water measured using single transpulmonary thermodilution reflects perioperative pulmonary edema induced by esophagectomy.

Pulmonary edema is the most frequent postoperative complication following esophagectomy for thoracic esophageal cancer. We enrolled 23 patients who underwent esophagectomy with extended lymph node dissection for thoracic esophageal cancer in a prospective observational clinical trial. We used the PiCCO device to measure extravascular lung water with the aim of determining whether it correlates with the respiratory index and whether it is predictive of pulmonary complications. Based on constant criteria, the tracheal tubes of 11 patients were removed on the morning of postoperative day 1 (extubation group), while 12 patients remained intubated (intubation group). These two groups significantly differed in that all patients in the extubation group recovered without any pulmonary complications, whereas 4 patients (33%) in the intubation group developed pulmonary complications. The extravascular lung water measured using PiCCO correlated significantly with the respiratory index. In the intubation group, both extravascular lung water and respiratory index were elevated 12 h after surgery and were even higher 24 h after surgery. The extravascular lung water measured using PiCCO reflects the level of postoperative pulmonary edema and predicts the pulmonary complications induced by esophagectomy with extended lymph node dissection.

Involvement of IL-18 and soluble fas in patients with postoperative hepatic failure.

We measured the levels of tumor necrosis factor alpha (TNF-alpha), interleukins (IL)-6 and -18, and soluble Fas (sFas) in 11 patients with postoperative hepatic failure and assessed whether IL-18-mediated apoptosis is involved in the onset of liver dysfunction. The serum TNF-alpha, IL-18, and sFas levels were significantly higher in patients with sepsis as a complication than in those without sepsis. The TNF-alpha and IL-18 levels were significantly higher in nonsurvivors than in survivors. Significant correlations were observed between TNF-alpha and IL-6, between TNF-alpha and IL-18, and between TNF-alpha and sFas levels. These results showed that Fas-mediated hepatocyte apoptosis functions as an important mechanism responsible for the onset of postoperative hepatic failure in humans. They especially suggested that IL-18 and TNF-alpha function both as apoptosis-promoting factors and as apoptosis-inhibiting factors, depending on the conditions to which hepatocytes are subjected.

Pneumatic stabilization for flail chest injury: an 11-year study.

The use of prolonged mechanical ventilation in the treatment of flail chest injury may increase the incidence of pulmonary morbidity. The aim of this study was to examine the results of performing internal pneumatic stabilization in our hospital. A retrospective review of the medical records of 59 patients with flail chest injury who presented within an 11-year period was conducted. During the second half of the period examined, we routinely adopted three characteristic procedures in the treatment of flail chest injury, namely, pressure support on spontaneous breathing, continuous positive airway pressure via a mask, and respiratory physical therapy by physical therapists. We compared the background, prognosis, and methods of treatment for flail chest injury before and after the introduction of these three procedures. A marked decline in the duration of endotracheal intubation and controlled mechanical ventilation, and in the frequency of pulmonary morbidity, was evident following the introduction of the above procedures.

Effects of milrinone on platelet aggregation in swine with pulmonary hypertension.

PURPOSE: The purpose of this study was to investigate whether the effect of milrinone on platelet aggregation was related to the selectivity of vasodilation vasculature in a swine model with PH. MATERIALS AND METHODS: To induce pulmonary hypertension, we injected two sets of acid-washed glass beads in 15 swine, which were divided into two groups (those receiving milrinone or not) and compared with each other. RESULTS: The induction of pulmonary hypertension decreased the platelet count and increased the plasma levels of thromboxane B2 and 6-keto-prostaglandin F1alpha. CONCLUSION: A locally high concentration of prostaglandin I2, at least in part, may produce selectivity of vasodilation in the pulmonary vasculature.

Milrinone improves arterial oxygenation in dogs with acute lung injury induced by oleic acid.

The aim of the study was to investigate effects of milrinone on pulmonary permeability in dogs with acute lung injury induced by oleic acid. To induce acute lung injury, we administered 0.08 mg/kg of oleic acid to 19 adult mongrel dogs and then measured hemodynamic parameters and performed blood gas analysis. An injection of oleic acid depressed the mean arterial pressure, cardiac index, and arterial oxygenation. Dogs were divided into three groups: six received a bolus of milrinone (50 microg/kg) followed by a continuous (0.5 microg/kg/min, low-dose), seven received a bolus (100 microg/kg) followed by a continuous (1.0 microg/kg/min; i.e., a low-dose twice; high-dose), and six no milrinone (control). Milrinone administration improved the cardiac index and arterial oxygenation and simultaneously depressed the intrapulmonary shunt fraction and the extravascular thermal lung water as extravascular water content of the lung. These changes produced by milrinone are different according to the doses. In conclusion, milrinone acts on the capillary endothelium and inhibits an accumulation in the extravascular water content of the lung, which may induce an improvement in arterial oxygenation. Milrinone may also improve arterial oxygenation through an inhibition of platelet aggregation and chemical mediators that are released from platelets. The latter mechanism also may improve arterial oxygenation, and the exact property responsible for causing the effect of milrinone has not yet been identified.

Cost containment: the Pacific. Japan.

The Japanese healthcare system is structured to provide universal healthcare access to the entire Japanese population via a constitutional guarantee. Increasing costs within the Japanese healthcare system are largely attributable to the country's rapidly aging population. Intensive care services are provided primarily in large tertiary care hospitals by a relatively small cadre of dedicated critical care physicians. Triage pressure is high in many Japanese hospitals due to a relatively small proportion of ICU beds. As a result, few patients are admitted to the ICU at low risk of adverse outcome or monitoring. Costs associated with providing critical care are poorly understood because of current hospital cost accounting systems. Critical care costs have only recently become an area of concern. Nevertheless, critical care physicians are taking steps to more fully understand severity of illness, clinical outcome, and utilization of resources in order to effectively guide healthcare policy and resource allocation decisions impacting Japanese critical care.

Changes in the parameters of oxygen metabolism in a clinical course recovering from potassium cyanide.

Poisoning with potassium cyanide is usually fatal because of the inhibition of cytochrome oxidase. The parameters of oxygen metabolism in a patient with cyanide poisoning who was admitted in a coma with seizures was monitored. The administration of amyl nitrite and sodium thiosulfate led to a rapid improvement: the parameters reflecting oxygen metabolism improved and the plasma level of cyanide decreased. The patient revived 1 1/2 hours after treatment. The arterial ketone body ratio (AKBR), which is the ratio of acetoacetate to beta-hydroxybutyrate in arterial blood and which reflects the redox state in liver mitochondria, improved dramatically following treatment. Because the AKBR changes in relation to electron transport in liver mitochondria, it seems to be a logical parameter for evaluating the effect of potassium cyanide poisoning on electron transport. The AKBR also reflects the efficacy of treatment for cyanide poisoning.

Effects of milrinone on lung water content in dogs with acute pulmonary hypertension.

To evaluate the effects of milrinone (MIL) on hemodynamics and lung water content, we used 10 mongrel dogs with pulmonary hypertension (PH). To induce pulmonary hypertension, we administered two injections of glass beads stirred in saline to dogs. Mean pulmonary arterial pressure (PAP) and pulmonary vascular resistance significantly increased following induction. Milrinone, which inhibits cyclic AMP phosphodiesterase-(PDE) demonstrated pulmonary vasodilation, indicated a reduction in these two parameters. To clarify the drug mechanism, we measured lung water content as extravascular lung thermal volume (ETVL) using a thermo/sodium double-indicator dilution method. The induction of pulmonary hypertension produced a transient reduction in extravascular lung thermal volume. The parameter remained constant following milrinone administration, whereas the control showed a gradual increase. Of the 10 dogs, five were killed to measure gravimetrically the volume of lung water content as a comparison with extravascular lung thermal volume. We concluded that milrinone produced pulmonary vasodilation which induced a reduction in the transmural capillary pressure gradient according to Starling's hypothesis. This study suggests that the reduction in the transmural pressure gradient induced by milrinone may also prevent the re-elevation in extravascular lung thermal volume. Milrinone increases the cyclic AMP level in the endothelium and in the platelet which may affect either directly or indirectly the permeability of capillary endothelium.

[Clinical course of asthmatics with severe asthma attack].

This study was conducted on 39 patients whose severe attacks of bronchial asthma with disturbance of consciousness required admission to the ICU of our hospital between 1984 and 1989. Among the 39 patients, there were 16 deaths. Most patients collapsed suddenly at home and were taken to our hospital. Arterial blood gas analysis at the time of admission to the ICU revealed that the PaO2 levels were as high as 252.6 +/- 57.6 (mean +/- S.E.) Torr in non-survivors and 221.0 +/- 29.7 Torr in survivors, with no significant difference because of prior oxygen therapy in almost all cases. Systolic blood pressure was 14.8 +/- 10.8 (mean +/- S.E.) mmHg, with marked circulatory disturbance in the fatal cases. Most patients displayed marked disturbance of consciousness, but maintenance of blood pressure led to recovery without sequelae despite marked disturbance of consciousness in most patients.

An initial comparison of intensive care in Japan and the United States.

OBJECTIVE: The objective of this study was to compare the utilization of, and outcome from, critical care services in selected medical centers providing secondary and tertiary care in the United States and Japan. DESIGN: Prospective data collection on 1,292 patients from each of the participating Japanese study hospitals in 1987 to 1989 and compared with the 5,030 patients in the United States 1982 Acute Physiology and Chronic Health Evaluation (APACHE II) database used to develop the APACHE II equation. Detailed organizational characteristics of the participating ICUs and hospitals were also obtained. SETTING: Data collection took place in the ICUs of 13 U.S. hospitals and six Japanese hospitals. PATIENTS: Data were collected on consecutive, unselected patients from medical, surgical, and mixed medical/surgical critical care units, with a spectrum of medical and surgical diagnoses. MEASUREMENTS AND MAIN RESULTS: U.S. and Japanese ICUs have a similar array of diagnostic and therapeutic modalities. Only 2% (range 0.6 to 3.5) of beds in Japanese hospitals were designated to intensive care. The organization of the Japanese and U.S. ICUs varied by hospital. There were significantly fewer women admitted to Japanese ICUs and a substantially lower proportion of low-risk-of-death patients. Despite a rapidly aging population, there were relatively fewer elderly patients with chronic health ailments in the Japanese ICU population (8%) compared with the U.S. cohort (18%). CONCLUSIONS: In this sample of hospitals, similar high-technology critical care is available in the United States and Japan. Variations in utilization between the two countries represent differences in case mix and bed availability. The APACHE II equation stratified patients in the Japanese patient cohort across the full spectrum of increasing severity of illness.

Comparative effects of dopamine and dobutamine on the pulmonary haemodynamic response to hypoxia in dogs ventilated with a hypoxic gas mixture.

1. The effects of dopamine and dobutamine on the pulmonary haemodynamic response to hypoxia were studied in nine anaesthetized dogs under hypoxaemia induced by ventilation with hypoxic gas mixture. 2. From the present study, only dopamine infusion reduced arterial oxygenation during hypoxic hypoxaemia, whereas catecholamine maintained it at the same level during normoxaemia. 3. A redistribution of perfusion to the pulmonary vasculature may be related to a reduction of arterial oxygenation with dopamine infusion during hypoxic hypoxaemia. 4. It is presumed that an increase in pulmonary blood flow would emphasize an inhibition of hypoxic pressor response in the pulmonary vasculature, which may not be a direct effect of dopamine.

[Improving effect of the synthetic protease inhibitor E-3123 on experimental DIC in dogs].

Disseminated intravascular coagulation (DIC) is a severe syndrome associated with generalized, intractable bleeding and multiple organ failure. Synthesized protease inhibitors such as gabexate mesilate and nafamostat mesilate show an improving effect on DIC, which develops by a chain reaction involving the coagulation, fibrinolysis, complement and kallikrein systems. Experimental DIC was developed in Beagle dogs by infusion of 150 U/kg tissue thromboplastin (Group I), and the improving effect of a new synthetic protease inhibitor, E-3123, was examined. The following groups of animals were treated with drugs: Group II (n = 4) was given with 5 mg/kg/hr of E-3123; group III (n = 4) was given 10 mg/kg/hr of E-3123; and group IV was given 6 mg/kg/hr of gabexate mesilate (GM). Although improvement of the hemodynamics or peripheral circulation was not apparent, a slight, but insignificant, improvement of lactate/pyruvate was noted in the treated groups. On the other hand, the hemostatic abnormalities such as prolongation of prothrombin time and activated thromboplastin time; decreases of platelet count, fibrinogen and alpha 2-antiplasmin; and increases of fibrin degradation products were significantly improved in the treated groups. These results indicate that E-3123 is effective for improving experimental DIC, and it is suggested that E-3123 is applicable for the treatment of clinical DIC.

Effects of milrinone on pulmonary vasculature in normal dogs and in dogs with pulmonary hypertension.

OBJECTIVE: To study the effects of milrinone on pulmonary vasculature. BACKGROUND: It has been suggested that bipyridines or their derivatives may have a selective pulmonary vasodilation effect. METHODS: Preliminary study: milrinone administration to 12 normal dogs (low dose [bolus 75 micrograms/kg for 5 min followed by a continuous infusion at 0.75 micrograms/kg.min, n = 6]; high dose [bolus 150 micrograms/kg for 5 min followed by continuous infusion at 1.5 micrograms/kg.min, n = 6]). Main study: milrinone administration to 18 dogs with pulmonary hypertension due to pulmonary embolism induced by a massive injection of autologous muscle cubes. The pulmonary hypertension dogs were divided into three groups: a) group E (n = 6) received embolization only, as control; b) group L (n = 6) received low-dose milrinone; and c) group H (n = 6) received high-dose milrinone, equivalent to the preliminary study group. Hemodynamic measurements and blood samplings were obtained at baseline and at 15, 30, and 60 min after start of milrinone infusion. RESULTS: Milrinone did not change mean pulmonary artery pressure (MPAP) in normal dogs. Milrinone decreased MPAP significantly in dogs with pulmonary hypertension. Pulmonary vascular resistance index remained at an almost constant level in normal dogs, but decreased significantly in dogs with pulmonary hypertension. Mean arterial pressure was maintained at a constant level in all groups. High-dose milrinone administration decreased systemic vascular resistance index (SVRI) significantly; low-dose milrinone administration decreased SVRI slightly. CONCLUSIONS: Milrinone may have a selective pulmonary vasodilatory effect only in dogs with pulmonary hypertension. The mechanism that produced a selectivity on pulmonary vasculature in dogs with pulmonary hypertension is unknown. However, an inhibition of platelet aggregation may decrease the MPAP resulting from an increase in cAMP caused by milrinone. Further studies are needed to resolve the pulmonary vasodilatory effect of milrinone in dogs with pulmonary hypertension.

Changes in hemodynamics and myocardial metabolism following discontinuation of a dopamine or dobutamine infusion.

Hemodynamics and myocardial metabolism were studied in 20 anesthetized dogs following discontinuation of a dopamine (DA) or dobutamine (DB) infusion. Both groups showed significant decreases in HR, AP, dP/dt, CI, MBFI, and MVO2. Discontinuation of DA decreased lactate extraction, whereas this did not occur with DB. The arteriocoronary venous differences in reduction-oxidation electrical potential (delta Eh) decreased significantly immediately following an abrupt discontinuation of the DA infusion, whereas DB maintained delta Eh at a constant level during and following infusion. Thus, aerobic metabolism was maintained following the discontinuation of DB, and anaerobic metabolism in the myocardium was accelerated immediately following discontinuation of the DA infusion. Although the mechanism that produces the differences observed between DA and DB following discontinuation is not understood, it may result from stimulation of alpha 1-receptors in the myocardium, produced by the residual high level of myocardial tissue norepinephrine (NE) following the termination of DA. A high tissue level of NE combined with a low plasma level of DA may cause an oxygen imbalance of the myocardium, demonstrated by an increase in myocardial oxygen demand and by a reduction in coronary blood flow. It is speculated that this mechanism of oxygen imbalance is a possible explanation for the anaerobic metabolism observed following DA discontinuation.

[Clinical results of selective treatment for flail chest].

A better understanding in pathophysiology of flail chest has brought an evolution to the principles of it's management. The methods of stabilization changed from surgical to pneumatic measures and now, a concept of conservative treatment is recognized. Adhering to our protocol for flail chest, which essentially limits mechanical ventilation, we have prospectively treated 36 patients since 1981. The patient were divided into two groups according to their need for mechanical ventilation. There were 16 patients (44.4%) in a group treated in conservative manner and with no mechanical ventilation (Group A). There were 20 patients (55.6%) in a group treated by mechanical ventilation (Group B). Group A had 6.2% incidence of pneumonia, 3.6 days average stay in ICU and mortality rate of 0%. Group B had 75% pneumonia, 22.5 days average in ICU and 15% mortality. Group B patients required respiratory support for 14 days average, which was not reduced by surgical stabilization. Restrictive pulmonary disturbance in group A was milder than that of group B, and this again was not affected by surgical stabilization. We conclude that 40% of flail chest are controllable without mechanical ventilation and that the result of this conservative therapy is superior to any other treatments.

Vasodilatory effects of milrinone on pulmonary vasculature in dogs with pulmonary hypertension due to pulmonary embolism: a comparison with those of dopamine and dobutamine.

1. The limited therapeutic role of pulmonary vasodilation reflects lack of their selectivity for the pulmonary vasculature, and many drugs have been evaluated for effectiveness; however, none has gained widespread clinical use. 2. Milrinone (MIL) is a newly synthetized phosphodiesterase inhibitor, which has potent positive inotropic and vasodilatory effects. 3. The present study shows the effects of MIL on the pulmonary circulation in dogs with pulmonary hypertension due to autologous muscle-induced pulmonary embolism, and also demonstrates a comparison with those of dopamine and dobutamine. 4. As MIL showed potent vasodilatory effects on the pulmonary vasculature, it had a potential clinical role in the treatment of pulmonary hypertension.

Selective pulmonary vasodilatory effect of ZSY-27 in dogs with pulmonary hypertension due to pulmonary embolism.

The pulmonary vasodilator effect of ZSY-27, a newly synthesized phosphodiesterase inhibitor, was studied in dogs with pulmonary hypertension resulting from autologous muscle-induced pulmonary embolism (PE). A bolus injection of ZSY-27 (1 mg/kg) significantly decreased mean pulmonary arterial pressure from 32 +/- 4 to 24 +/- 5 mm Hg and pulmonary vascular resistance index from 415 +/- 60 to 316 +/- 94 dyne.sec/cm5.m2. ZSY-27 did not change mean arterial pressure. The cardiac index was slightly increased and the systemic vascular resistance index was slightly decreased after ZSY-27 injection, but these changes were not statistically significant. This study suggests that ZSY-27 is a possible therapeutic agent for pulmonary hypertension secondary to PE.

Extracorporeal lung assist for patient with hypercapnia due to status asthmaticus.

A 62-year-old female was brought to our emergency room in status asthmatics. She needed mechanical ventilation because of hypercapnia. However, effective mechanical ventilation was difficult because of severe airflow obstruction. Instead of conventional mechanical ventilation, we used extracorporeal lung assist (ECLA) to prevent barotrauma and lung tissue damage, and to reduce the doses of sedatives and muscle relaxants needed.

Impaired effect of dopamine on cardiac output during octopamine infusion.

The hemodynamic effects of octopamine (OCT) were studied before and during dopamine (DA) infusion in six normal dogs. Before OCT infusion, DA significantly increased cardiac index (CI) from 3.24 +/- 0.20 to 4.90 +/- 0.30 L/min X m2 and significantly decreased systemic vascular resistance index (SVRI) from 3700.2 +/- 212.5 to 2618.3 +/- 156.6 dyne X sec/cm5 X m2, without changing heart rate. During OCT infusion, DA failed to increase CI or decrease SVRI; however, it significantly increased heart rate from 153.3 +/- 12.9 to 183.0 +/- 17.0 beat/min. This suppression of a DA-related increase in cardiac output may explain why DA is ineffective in those septic patients with elevated plasma OCT levels.