Continuous blood purification is now widely applied in many ICUs for continuous renal replacement therapy (CRRT) and its efficacy in the treatment of acute renal failure is now widely accepted. Of the various types of continuous blood purification methods available, such as continuous hemofiltration (CHF) and continuous hemodialysis (CHD), continuous hemodiafiltration (CHDF) has gained the popularity in critical care in Japan. However, the efficacy of CHDF in removing cytokines for non-renal indications, such as sepsis, severe acute pancreatitis and ARDS, remains controversial. We have reported that the clearance of various cytokines with CHDF positively and significantly correlates to pre-CHDF blood levels. The higher the cytokine blood level is, the larger its clearance with CHDF is. We also found that the blood level of cytokines significantly decreased with 3 days of CHDF in patients whose pre-CHDF blood levels were high, but that the blood level of cytokines did not decrease with 3 days of CHDF in patients whose pre-CHDF blood levels were low. We also found that the degree of the decrease in the blood level of cytokines was significantly correlated to the degree of improvement in organ dysfunction, indicating a clinical benefit of cytokine removal with CHDF. The removal of cytokines by CHDF seems to be not only through convection and diffusion which are the expected mechanisms of substance removal with CHDF, but also through the adsorption of cytokines to the hemofilter membrane. The polymethyl methacrylate membrane (PMMA) hemofilter is the best choice for CHDF in this regard since the PMMA hemofilter can adsorb cytokines better than hemofilters using other types of membranes.
In conclusion, CHDF is effective in removing cytokines from the bloodstream when the pre-CHDF cytokine blood levels of the patient are high and when CHDF is performed with a PMMA membrane hemofilter. Our results clearly indicate that CHDF can be applied for non-renal indications aimed at removing causative humoral mediators such as cytokines.

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We reviewed the effectiveness of the removal of cytokines by blood purification. Continuous hemofiltration (CHF) and hemodiafiltration (CHDF) are not effective in removing cytokines from the blood because the clearance of cytokines is small, there is less removal with CHF or CHDF than with endogenous removal, and cytokines are synthesized during contact with the CHF or CHDF membranes. Since most of the clearance by CHF and CHDF is due to adherance to the membrane, it may be possible to decrease cytokines by increasing blood flow and by increasing the surface area of the filter. Membranes with large pores increase the filtration rate of cytokines, but do not decrease the plasma concentration of cytokines. CHF and CHDF also have adverse effects in that they remove anti-inflammatory cytokines as well as inflammatory cytokines. Blood purification by plasma exchange (PE) or polymyxin B-immobilized fibers (PMX) does not decrease the plasma concentration of cytokines.
It was concluded that blood purification by CHF, CHDF, PE or PMX is not effective in removing circulating cytokines. A multicenter control randomized trial is needed to see if blood purification is effective for hypercytokinemia.

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To avoid the need for endotracheal intubation and mechanical ventilation with higher airway pressure, we applied noninvasive positive pressure ventilation (NIPPV) and position change (postural respiratory therapy, PRT) on 12 patients with severe acute respiratory failure (ARF, PaO₂/F_IO₂<200mmHg), and evaluated retrospectively the patients' prognostic factors in NIPPV combined with PRT.
Patients were administered mask CPAP (3-10cmH₂O) with or without pressure support (2-10cmH₂O)and clinically managed in the right or left anterolateral position, whichever showed a better improvement in the PaO₂/F_IO₂ ratio (P/F) compared to the supine position. They were changed into the prone position for less than 2 hours several times a day as essential treatment for dorsal dependent lung lesions. We continued this method as long as patients 1) showed no respiratory fatigue, 2) remained conscious, cooperative and able to cough safely, and 3) showed pulmonary oxygenation improvement by changing positions.
When we turned patients into an anterolateral or prone position from supine soon after ICU admission, 11 of 12 patients (92%) showed improvement in pulmonary oxygenation, and 8 (67%) no longer met the criteria for endotracheal intubation and mechanical ventilation (P/F<200). Six patients successfully recovered in several days with NIPPV combined with PRT (successful group), but the other 6 required intubation and mechanical ventilation (failure group). There were no statistically significant differences between the failure group and successful group on ICU admission with respect to APACHE II score (20.1±5.0 vs 18.0±2.4), risk of hospital death (37.2±16.1 vs 29.6±7.5%), lung injury score (3.3±0.7 vs 2.8±0.6), and lowest P/F (114.0±34.1 vs 135.3±31.1). The duration from onset was significantly longer (3.3±0.8 vs 2.0±0.9 days), the respiratory rate (RR) higher (46.7±6.9 vs 33.8±7.8min^-1), and PaCO₂ and base excess (BE) significantly lower (PaCO₂, 27.0±5.3 vs 32.2±2.1mmHg; BE, -6.9±4.2 vs-2.1±1.6) in the failure group. The patients in the successful group had accelerative P/F recovery (turning point)on the 3.7±1.5 ICU day and their P/F in all positions exceeded 300 within 5.7±1.8 days. All patients in the failure group had signs of progressive systemic inflammation including recurrent high fever, endotoxemia, serum CRP elevation. They were intubated and mechanically ventilated from 2.5 hours to 3 days after ICU admission due to respiratory fatigue, septic shock and drowsiness.
We conclude that patients with acute respiratory failure who are managed with NIPPV combined with PRT have a good prognosis when they (1) are not in severe metabolic acidosis, (2) are in the early stages of acute respiratory failure (within 3 days from onset), (3) show no signs of deteriorating systemic inflammation, and (4) have no severe tachypnea or severe hyperventilation (RR<40min^-1, PaCO₂>30mmHg).

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We measured intracellular pH (pHi) and Ca⁺⁺ (Ca⁺⁺i) in cultured cells by giving acetazolamide (AZ) to show that carbonic anhydrase regulates CO₂ in the cells and adjusts pHi and Ca⁺⁺i.
MK-1 cells were cultured in the incubation medium with or without AZ and the excited fluorescence of BCECF for pH and fura-2 for Ca⁺⁺ were measured using a microspectrofluorometer.
While extracellular pH (pHe) was 7.35∼7.45, the change in the correlation line between pHe and pHi/Ca⁺⁺i showed that pHi and Ca⁺⁺i were reduced by the addition of AZ into the incubation medium.
It was concluded from the reduction of pHi and Ca⁺⁺i by AZ that pHi and Ca⁺⁺i are controlled by the retention of intracellular CO₂ induced by the inhibition of carbonic anhydrase.

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Olprinone, a novel cardiotonic agent, is a potent phosphodiesterase III inhibitor. However, the effects of this agent on the hepatosplanchnic circulation have not been well investigated. In the present study, we measured hepatic venous oxygen saturation (ShvO₂) and examined the effects of olprinone on hepatosplanchnic oxygen dynamics in patients following cardiac surgery.
We examined eleven patients undergoing elective cardiac surgery in this study. A 7.5 Fr oximeter catheter was placed in the hepatic vein via the right femoral vein after the operation, and the study was performed after obtaining stable systemic hemodynamics in ICU. The patients were administered 0.3μg·kg^-1·min^-1 of olprinone for two hours. We did not change hemodynamic interventions throughout the study. Arterial and hepatic venous blood gas analysis and hemodynamic measurements using a pulmonary artery catheter were performed before and after the drug infusion. We calculated systemic oxygen delivery and consumption. The oxygen extraction ratio of systemic and blood flow was 26.4±18.8%, which was significantly greater than the change in cardiac index.
Our results could not be conclusive due to the lack of a control experiment, however they suggest that olprinone facilitates splanchnic blood flow and is beneficial for protecting splanchnic organs after cardiac surgery.

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Type II phospholipase A₂ (PLA₂) is an enzyme of 14kD. The increased plasma activity of PLA₂ plays a significant role in the pathophysiology of sepsis. This study was carried out to determine if PLA₂ could be removed by continuous hemodiafiltration (CHDF). We assayed the plasma activity of PLA₂ and the clearance of PLA₂ by CHDF in patients with septic acute renal failure. CHDF was performed using a polyacrylonitrile (PAN) hemofilter. The blood flow rate through the extracorporeal system was 60-100ml·min^-1 with a dialysis fluid rate of 500ml·hr^-1. The ultrafiltration rate was 500ml·hr^-1 and the replacement solution was administered at a rate of 350-500ml·hr^-1. The extracorporeal circuit was protected against coagulation with nafamostat mesilate. Blood and ultrafiltrate samples were collected before starting CHDF (0hrs), and 12 hours (12hrs) and 24 hours (24hrs) after starting CHDF. Arterial PLA₂ activity was 839±684pmol·min^-1·ml^-1 at 0hrs, 642±414pmol·min^-1·ml^-1 at 12hrs and 573±355 pmol·min^-1·ml^-1 at 24hrs, respectively. The changes in arterial PLA₂ activity were not statistically significant. PLA₂ activitiy at the entry port of the filter was significantly higher than that at the exit port at 24hrs. The clearance of PLA₂ activity from the ultrafiltrate was 0.09±0.06ml·min^-1 at 12hrs and 0.15±0.15ml·min^-1 at 24hrs. The clearance of PLA₂ activity from the blood was 27±29ml·min^-1 at 12hrs and 23±12ml·min^-1 at 24hrs. The results suggest that plasma PLA₂ can be removed to some extent, but arterial PLA₂ activity is not significantly decreased. Further investigation is needed to develop an efficient technique to remove plasma PLA₂.

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We compared the performance of a continuous intra-arterial blood gas monitor with measurements in a standard blood gas analyzer in 32 patients at pre-bypass, on- bypass, post- bypass, and postoperative days 1 and day 2 of cardiac surgery. The overall bias±precision values were 0.04±0.05 for pH. The bias values were within±0.3 for PaCO₂ except for the on-and post-bypass phases. The bias values were within±3.4 for PaO₂ except for the on- and postbypass phases. Correlations were found between continuous intra-arterial blood gas monitor values and standard blood gas analyzer values for almost all measurements of pH, PaCO₂ and PaO₂ except for the on- bypass phase of PaCO₂. We concluded that care must be taken when evaluating pH, PaCO₂ and PaO₂ during cardiopulmonary bypass with this continuous intra-arterial blood gas analyzer.

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The patient, a 65-year-old-male, had chest pain while sleeping, and visited our department the next morning. Systolic blood pressure was 90mmHg, and pansystolic murmurs in the left sternal boundary and moist rales in the lungs were detected by auscultation. ST elevation of II, III, and aV_F was observed by electrocardiography, and ventricular septal rupture was found by echocardiography. The Qp/Qs was 2.5, and the left-to-right shunt rate was 62%. Complete occlusion of the right coronary artery was observed by coronary angiography. Intra-aortic balloon pumping was performed and the ventricular septal rupture was closed with a patch on the same day. Partial rupture of the posterior papillary muscle was found during surgery, and muscle bundles with tendinous cords were sutured with healthy papillary muscle. On the 10th day after operation, complete rupture of the posterior papillary muscle occurred below the site where the posterior papillary muscle had been sutured. On the 11th postoperative day, mitral valve plasty was performed, resulting in stable hemodynamics. The patient was discharged on the 39th day after operation. This is the second case reported in Japan of myocardial infarction accompanied by ventricular septal rupture and complete rupture of the posterior papillary muscle, and the first case successfully managed by emergent operation.

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Acute arterial occlusion disease has various pathophysical states and often is associated with myonephropathic metabolic syndrome (MNMS). We carried out local perfusion by limb wash-out for an extended period in two cases of acute arterial occlusion of the lower extremities. One patient developed high aortic occlusion after an operation for a ruptured abdominal aortic aneurysm. The other patient had a right iliac arterial occlusion. The first patient died of multiple organ failure (MOF), but an improvement in postoperative condition was seen. The other patient survived. The postoperative course in these patients suggested that local perfusion by limb wash-out was effective. MNMS has many pathogenic states and phases. Local perfusion by limb wash-out may be effective for the treatment of acute arterial occlusion disease in which acidosis, hyperpotassium and myogloblinemia are present. This method may be used to improve the treatment of MNMS.

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A case of severe digoxin poisoning is reported. A 46-year-old male suffering from nausea, vomiting and fright after ingesting fifty pills of the cardiac medicine, Methyldigoxin, by mistake, was transferred to our emergency unit. The patient had a serum digoxin level of 46.5ng·ml^-1 with hyperkalemia (potassium level of 7.8mEq·l^-1) upon admission to the Intensive Care Unit (ICU). The electrocardiogram (ECG) showed fatal arrythmia including complete atrio-ventricular block, bradycardia and ventricular tachycardia. The trachea was intubated under sedation and analgesics and controlled mechanical ventilation was performed because of his agitation and hypoxemia. A temporary pacing wire was placed in the right ventricle. Direct hemoperfusion (DHP) was attempted at the same time to help eliminate the massive dose of digoxin. Hyperkalemia was treated with glucose-insulin, ion-exchange and hemodialysis (HD). The serum digoxin level fell abruptly to 16.6ng·ml^-1 within six hours of admission to the ICU. It took three days to reach a therapeutic level of serum digoxin, four days to return to a normal sinus rhythm in the ECG and ten days to leave the ICU. DHP is generally not an effective treatment for digitalis intoxication resulting from long term digoxin administration, but it may be effective in the treatment of acute severe digoxin poisoning after oral intake in the early phase.

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