Case Report: Pulmonary Tumor Thrombotic Microangiopathy in a Cervical Cancer Patient.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rapidly progressive and often fatal pulmonary disease induced by tumor emboli within the small pulmonary arteries. PTTM presents clinically as progressive hypoxia and pulmonary hypertension. Most cases of PTTM are caused by an adenocarcinoma of the stomach. We present the first case report of PTTM caused by cervical squamous cell carcinoma. An 82-year-old woman presented with vaginal bleeding and exertional dyspnea. A cervical mass biopsy showed squamous cell carcinoma. Computed tomography revealed ground glass opacity of the bilateral peripheral lung fields. Hypoxia and pulmonary hypertension gradually worsened after admission. Treatment for acute heart failure was started, but was ineffective. She died of respiratory failure 31 days after admission. She was diagnosed at autopsy as having PTTM induced by cervical squamous cell carcinoma. PTTM needs to be considered in any patient with advanced cancer and lung-related issues to rule out metastatic disease, even in the absence of imaging findings.

Amino acid balance with extended daily diafiltration in acute kidney injury.

BACKGROUND: The impact of hybrid dialysis therapies on amino acid (AA) balance in critically ill patients with acute kidney injury is unknown. METHODS: We examined prospectively the AA balance with extended daily diafiltration (EDDF). RESULTS: We studied 7 patients. AA clearances with EDDF ranged from 21.6 ml/min (tryptophan) to 66.9 ml/min (taurine). AA loss was 4.2 (IQR 1.4-12.3) g/day and 4.5% of daily protein intake for patients on enteral nutrition (EN). Percentage AA loss per hour on EDDF was highest for glutamine (32.1%) and lowest for glutamic acid (0.8%). Blood AA levels correlated with corresponding EDDF losses. Median total nitrogen appearance was 25.0 (IQR 20.6-29.3) g/day for patients on EN. This resulted in a negative nitrogen balance of -10.7 (IQR -16.6 to -1.4) g/day, of which 6.5% was attributable to AA loss. CONCLUSIONS: AA loss with EDDF was limited, but with much individual variability, and contributed to a strongly negative daily nitrogen balance.

Time to initiation of treatment with polymyxin B cartridge hemoperfusion in septic shock patients.

BACKGROUND: We investigated whether early initiation of hemoperfusion with a polymyxin B cartridge (PMX) after the diagnosis of septic shock could improve the clinical outcome. METHODS: A prospective, open-labeled, multicenter cohort study was performed at intensive care units in Japan. 41 patients received PMX within 6 h after the diagnosis of septic shock (early group) and 51 patients were treated after 6 h (late group). RESULTS: The early group had a significantly shorter duration of ventilator support and also had a lower catecholamine requirement. PMX was effective for improvement of hypotension, hypoperfusion, the sequential organ failure assessment score, and pulmonary oxygenation regardless of the timing of its initiation. The 28-day mortality rate did not differ between the two groups. CONCLUSIONS: Early initiation of PMX shortened the duration of ventilator support and also reduced the catecholamine requirement, so early treatment of septic shock should achieve a better outcome.

Multicenter study of plasma diafiltration in patients with acute liver failure.

Plasma diafiltration (PDF) is a blood purification therapy in which simple plasma exchange (PE) is performed using a selective membrane plasma separator while the dialysate flows outside the hollow fibers. A prospective, multicenter study was undertaken to evaluate the changes in bilirubin, IL-18, and cystatin C, as well as the 28-day and 90-day survival rates, with the use of PDF according to the level of severity as measured by the Model for End-Stage Liver Disease (MELD) score. Twenty-one patients with liver failure were studied: 10 patients had fulminant hepatitis and PDF therapies were performed 28 times; 11 had acute liver failure with the therapy performed 96 times. Levels of total bilirubin, IL-18, and cystatin C decreased significantly after treatment. The 28-day survival rate was 70.0% and that at 90 days was 16.7%. According to the severity of the MELD score, each of the results compared well with the use of Molecular Adsorbent Recirculating System or Prometheus therapy. In conclusion, PDF appears to be one of the most useful blood purification therapies for use in cases of acute liver failure in terms of medical economics and the removal of water-soluble and albumin-bound toxins.

Comparison of hemostatic durability between N-butyl cyanoacrylate and gelatin sponge particles in transcatheter arterial embolization for acute arterial hemorrhage in a coagulopathic condition in a swine model.

This study was designed to compare the efficacy of transcatheter arterial embolization (TAE) with N-butyl cyanoacrylate (NBCA) or gelatin sponge particles (GSP) for acute arterial bleeding in a coagulopathic condition using a swine model. Four healthy swine were divided into two coagulopathic conditions: mild and severe. Five hemorrhages were created in each swine (10 hemorrhages per coagulopathy). Mild coagulopathy was achieved by bloodletting 10% of the total circulatory whole blood and preserving activated clotting time (ACT) less than 200 s (ACT < 200 s state); severe coagulopathy was achieved by bloodletting 30% and preserving ACT > 400 s (ACT > 400-second state). For each state, of ACT < 200 s or ACT > 400 s, TAE was conducted with GSP or NBCA to control five hemorrhages arising from artificially created renal and splenic injuries. Angiography immediately after TAE with GSP or NBCA showed complete occlusion in both coagulopathic conditions. In the ACT < 200-second state, follow-up angiography at 5-30 min after TAE with GSP or NBCA showed no evidence of recurrent hemorrhage. In the ACT > 400-second state, follow-up angiography showed recurrent hemorrhage in four (80%) of the five hemorrhages embolized with GSP and in one (20%) of the five hemorrhages embolized with NBCA. Microscopically, red thrombi were observed densely surrounding GSP in mild coagulopathy but were scarce in severe coagulopathy. In a condition with severe coagulopathy, TAE with NBCA was more effective in durability to cease active arterial bleeding than with GSP.

'Super high-flux' or 'high cut-off' hemofiltration and hemodialysis.

Recently, 'super high-flux' (SHF) or 'high cut-off' (HCO) membranes have been developed to increase the clearance of inflammatory mediators. In the experimental and clinical settings, SHF/HCO membranes appear to achieve greater clearance of inflammatory cytokines than conventional high-flux membranes. SHF/HCO membranes also restore immune cell function, attenuate hemodynamic instability and decrease plasma IL-6 levels. Moreover, SHF/HCO membranes can eliminate larger late-phase inflammatory mediators such as HMGB-1. Although albumin sieving coefficients with SHF/HCO membranes are greater than with conventional high-flux membranes, the daily amount lost is limited and can be replaced. Hemodialysis with SHF/HCO membranes can also achieve similar cytokine removal to hemofiltration with acceptable albumin losses. When strategies for sepsis or systemic inflammation treatment target middle molecular mediators, both SHF/HCO hemofiltration and hemodialysis appear feasible and safe and require further clinical investigation.

Hyperglycemia induced cell growth and gene expression via the serum response element through RhoA and Rho-kinase in vascular smooth muscle cells.

The impressive correlation between cardiovascular disease and alterations in glucose metabolism has raised the likelihood that atherosclerosis, heart failure, and type 2 diabetes may share common antecedents. Postprandial hyperglycemia has been shown to play an important role on the onset and development of heart failure and cerebral infarction in several large-scale clinical trials. Recently, chronic hyperglycemia has been reported to enhance the vasoconstrictor response by Rho-kinase. We have previously reported that phenylephrine enhanced the vasoconstrictor response in a spontaneous diabetes mellitus OLETF (Otsuka-Long-Evane-Tokushima fatty) rat model. However, the mechanism of hyperglycemia in these reactions, particularly the influence of hyperglycemia on the signal transduction pathway, is still not well understood. We, therefore, examined the effect of hyperglycemia on the cell growth and gene expression of rat aortic smooth-muscle cells (RASMCs). Hyperglycemia accelerated the growth of RASMCs in a concentration-dependent manner. Furthermore, the c-fos gene expression was also increased by hyperglycemia. Phenylephrine activated the c-fos gene expression. Hyperglycemia augmented the phenylephrine-induced c-fos gene expression synergistically in a dose dependent manner. The deletion analysis revealed that the c-fos serum response element (SRE) accounts for the c-fos gene expression. RhoA, and Rho-kinase were involved in hyperglycemia-induced c-fos gene expression. An HMG-CoA reductase inhibitor, Pitavastatin, inhibited these hyperglycemia-augmented reactions by inhibiting RhoA. Hyperglycemia itself increased the cell growth and gene expression. Furthermore, it modifies and augments the cell growth and gene expression by alpha1-AR-mediated stimulation. Statin might therefore be effective for the treatment of hyperglycemia-induced cardiovascular dysfunction.

Effects of saline or albumin resuscitation on standard coagulation tests.

AIMS: To explore whether fluid resuscitation with normal saline or 4% albumin is associated with differential changes in routine clinical coagulation tests. DESIGN: Substudy from a large double-blind randomised controlled trial, the SAFE (Saline versus Albumin Fluid Evaluation) study. SETTING: Three general intensive care units. PATIENTS: Cohort of 687 critically ill patients. INTERVENTION: We randomly allocated patients to receive either 4% human albumin or normal saline for fluid resuscitation, and collected demographic and haematological data. METHODS AND MAIN RESULTS: Albumin was administered to 338 patients and saline to 349. At baseline, the two groups had similar mean activated partial thromboplastin time (APTT) of 37.2 s (albumin) v 39.1 s (saline); mean international normalised ratio (INR) of 1.38 v 1.34, and mean platelet count of 244 x 10(9)/L v 249 x 10(9)/L. After randomisation, during the first day of treatment, the APTT in the albumin group was prolonged by a mean of 2.7 s, but shortened slightly by a mean of -0.9 s in the saline group. The INR did not change in either group, while the platelet count decreased transiently in both groups. Using multivariate analysis of covariance to account for baseline coagulation status, albumin fluid resuscitation (P = 0.01) and a greater overall volume of resuscitation (P = 0.03) were independently associated with prolongation of APTT during the first day. CONCLUSIONS: Administration of albumin or of larger fluid volumes is associated with a prolongation of APTT. In ICU patients, the choice and amount of resuscitation fluid may affect a routinely used coagulation test.

Evaluation of transcatheter arterial embolization with gelatin sponge particles, microcoils, and n-butyl cyanoacrylate for acute arterial bleeding in a coagulopathic condition.

PURPOSE: To evaluate the outcome of transcatheter arterial embolization with gelatin sponge particles, microcoils, and N-butyl cyanoacrylate (NBCA) for acute arterial hemorrhage in the setting of coagulopathy. MATERIALS AND METHODS: Coagulopathy is defined by a platelet count less than 5 x 10(4)/microL and/or International Normalized Ratio (INR) greater than 1.5. Forty-six patients (31 male patients; mean age, 62 years) with acute arterial hemorrhage in a coagulopathic condition were treated by transcatheter arterial embolization with gelatin sponge particle, microcoils, and NBCA. RESULTS: Because of failure of hemostasis or recurrent hemorrhage, 10 patients who underwent gelatin sponge particle embolization also received transcatheter arterial embolization with microcoils or NBCA embolization and two patients who underwent microcoil embolization also received transcatheter arterial embolization with NBCA. The gelatin sponge particle group consisted of 27 hemorrhagic arteries in 25 patients, the microcoil group had 20 in 20 patients, and the NBCA group had 16 in 13 patients. The mean platelet count and mean INR value were 5.8 x 10(4)/microL +/- 3.5 and 1.81 +/- 0.50, respectively. The primary hemostatic rate, recurrent hemorrhage rate, and mean treatment time for the gelatin sponge particle, microcoil, and NBCA groups were 67%, 23%, and 25 minutes +/- 10; 80%, 0%, and 37 min +/- 19; and 100%, 0%, and 9 min +/- 4, respectively. Primary and secondary hemostasis were achieved in 50 (80%) and 60 (95%) of the 63 hemorrhagic arteries, respectively. Three hemorrhagic arteries in which transcatheter arterial embolization failed were treated with surgical repair. CONCLUSIONS: Although transcatheter arterial embolization with microcoils took a greater amount of time, transcatheter arterial embolization with NBCA or microcoils was more effective and feasible than that with gelatin sponge particle in terms of hemostasis and prevention of recurrent hemorrhage in a coagulopathic condition.

Aldosterone induces interleukin-18 through endothelin-1, angiotensin II, Rho/Rho-kinase, and PPARs in cardiomyocytes.

Aldosterone (Aldo) is recognized as an important risk factor for cardiovascular diseases. IL-18 induces myocardial hypertrophy, loss of contractility of cardiomyocytes, and apoptosis leading myocardial dysfunction. However, so far, there have been few reports concerning the interaction between Aldo and IL-18. The present study examined the effects and mechanisms of Aldo on IL-18 expression and the roles of peroxisome proliferator-activated receptor (PPAR) agonists in rat cardiomyocytes. We used cultured rat neonatal cardiomyocytes stimulated with Aldo to measure IL-18 mRNA and protein expression, Rho-kinase, and NF-kappaB activity. We also investigated the effects of PPAR agonists on these actions. Aldo, endothelin-1 (ET-1), and angiotensin II (ANG II) increased IL-18 mRNA and protein expression. Mineralocorticoid receptor antagonists, endothelin A receptor antagonist, and ANG II receptor antagonist inhibited Aldo-induced IL-18 expression. Aldo induced ET-1 and ANG II production in cultured media. Moreover, Rho/Rho-kinase inhibitor and statin inhibited Aldo-induced IL-18 expression. On the other hand, Aldo upregulated the activities of Rho-kinase and NF-kappaB. PPAR agonists attenuated the Aldo-induced IL-18 expression and NF-kappaB activity but not the Rho-kinase activity. Our findings indicate that Aldo induces IL-18 expression through a mechanism that involves, at a minimum, ET-1 and ANG II acting via the Rho/Rho-kinase and PPAR/NF-kappaB pathway. The induction of IL-18 in cardiomyocytes by Aldo, ET-1, and ANG II might, therefore, cause a deterioration of the cardiac function in an autocrine and paracrine fashion. The inhibition of the IL-18 expression by PPAR agonists might be one of the mechanisms whereby the beneficial cardiovascular effects are exerted.

Mechanical stretch induced interleukin-18 (IL-18) expression through Angiotensin subtype 1 receptor (AT1R) and endothelin-1 in cardiomyocytes.

Interleukin-18 (IL-18) is a proinflammatory cytokine with multiple biological functions. We and others have demonstrated that an increased level of circulating IL-18 is one of the risk factors for cardiovascular diseases. Endothelin-1 (ET-1) has been reported to be a potent hypertrophy-promoting factor through RhoA and Rho-Kinase. Mechanical stretch induces a hypertrophic response, partly through the production of ET-1 through Endothelin A receptor (ETAR). Moreover, it has also been reported that mechanical stretch induces cardiac hypertrophy through Angiotensin subtype 1 receptor (AT1R). However, the mechanism by which the IL-18 gene expression is regulated in cardiomyocytes has not yet been fully understood. This study was designed to elucidate the functional significance of IL-18 gene expression in response to mechanical stretch. Neonatal rat cardiomyocytes cultured on silicone dishes were subjected to stretch. The moderate 20% mechanical stretch resulted in the elevation of IL-18 expression in a time-dependent manner with the maximal level achieved 36 hours after the stretch. Olmesartan, AT1R antagonist inhibited stretch-induced IL-18 expression. ETAR blockade BQ123 inhibited stretch-induced IL-18 expression. However, the Endothelin B receptor (ETBR) receptor blockade BQ788 did not inhibit this reaction. ET-1 induced IL-18 expression, with a peak induction after 4 hours of incubation. These results might suggest that stretch stimulation of cardiomyocytes induced ET-1 and, subsequently, ET-1 up-regulated the IL-18 expression. Furthermore, Fasudil, a Rho-Kinase inhibitor, and Simvastatin, a HMG-CoA reductase inhibitor, led to a significant reduction in mechanical stretch-induced IL-18 expression. These results indicated, for the first time, that IL-18 expression is induced by mechanical stretch in cardiomyocytes via the ETAR, AT1R, and the Rho/Rho-K pathways. The induction of IL-18 from cardiomyocytes by mechanical stress might cause the deterioration of cardiac functions in autocrine and paracrine fashion. The inhibition of IL-18 expression induced by mechanical stress might be one of the mechanisms that account for the beneficial cardiovascular effects of AT1R antagonist, ETAR blockade, Statin, and Rho-Kinase inhibitor.

Ultrasound enhances retrovirus-mediated gene transfer.

Viral vector systems are efficient for transfection of foreign genes into many tissues. Especially, retrovirus based vectors integrate the transgene into the genome of the target cells, which can sustain long term expression. However, it has been demonstrated that the transduction efficiency using retrovirus is relatively lower than those of other viruses. Ultrasound was recently reported to increase gene expression using plasmid DNA, with or without, a delivery vehicle. However, there are no reports, which show an ultrasound effect to retrovirus-mediated gene transfer efficiency. Retrovirus-mediated gene transfer systems were used for transfection of 293T cells, bovine aortic endothelial cells (BAECs), rat aortic smooth muscle cells (RASMCs), and rat skeletal muscle myoblasts (L6 cells) with beta-galactosidase (beta-Gal) genes. Transduction efficiency and cell viability assay were performed on 293T cells that were exposed to varying durations (5 to 30 seconds) and power levels (1.0 watts/cm(2) to 4.0 watts/cm(2)) of ultrasound after being transduced by a retrovirus. Effects of ultrasound to the retrovirus itself was evaluated by transduction efficiency of 293T cells. After exposure to varying power levels of ultrasound to a retrovirus for 5 seconds, 293T cells were transduced by a retrovirus, and transduction efficiency was evaluated. Below 1.0 watts/cm(2) and 5 seconds exposure, ultrasound showed increased transduction efficiency and no cytotoxicity to 293T cells transduced by a retrovirus. Also, ultrasound showed no toxicity to the virus itself at the same condition. Exposure of 5 seconds at the power of 1.0 watts/cm(2) of an ultrasound resulted in significant increases in retrovirus-mediated gene expression in all four cell types tested in this experiment. Transduction efficiencies by ultrasound were enhanced 6.6-fold, 4.8-fold, 2.3-fold, and 3.2-fold in 293T cells, BAECs, RASMCs, and L6 cells, respectively. Furthermore, beta-Gal activities were also increased by the retrovirus with ultrasound exposure in these cells. Adjunctive ultrasound exposure was associated with enhanced retrovirus-mediated transgene expression in vitro. Ultrasound associated local gene therapy has potential for not only plasmid-DNA-, but also retrovirus-mediated gene transfer.

A pilot randomised controlled comparison of continuous veno-venous haemofiltration and extended daily dialysis with filtration: effect on small solutes and acid-base balance.

BACKGROUND AND AIMS: Continuous veno-venous haemofiltration (CVVH) is an established treatment for acute renal failure (ARF). Recently, extended intermittent dialytic techniques have been proposed for the treatment of ARF. The aim of this study was to compare these two approaches. SETTING: Intensive care unit of tertiary hospital. SUBJECTS: Sixteen critically ill patients with ARF. DESIGN: Randomised controlled trial. INTERVENTION: We randomised sixteen patients to three consecutive days of treatment with either CVVH (8) or extended daily dialysis with filtration (EDDf) (8) and compared small-solute, electrolyte and acid-base control. RESULTS: There was no significant difference between the two therapies for urea or creatinine levels over 3 days. Of 80 electrolyte measurements taken before treatment, 19 were abnormal. All values were corrected as a result of treatment, except for one patient in the CVVH group who developed hypophosphataemia (0.54 mmol/l) at 72 h. After 3 days of treatment, there was a mild but persistent metabolic acidosis in the EDDf group compared to the CVVH group (median bicarbonate: 20 mmol/l vs. 29 mmol/l: p=0.039; median base deficit: -4 mEq/l vs. -2.1 mEq/l, p=0.033). CONCLUSIONS: CVVH and EDDf as prescribed achieved similar control of urea, creatinine and electrolytes. Acidosis was better controlled with CVVH.

The effects of saline or albumin resuscitation on acid-base status and serum electrolytes.

OBJECTIVE: To test whether fluid resuscitation with normal saline or 4% albumin is associated with differential changes in acid-base status and serum electrolytes. DESIGN: Nested cohort study. SETTING: Three general intensive care units. PATIENTS: Six hundred and ninety-one critically ill patients. INTERVENTIONS: Randomization of patients to receive blinded solutions of either 4% human albumin or normal saline for fluid resuscitation. MEASUREMENTS AND MAIN RESULTS: Albumin was given to 339 patients and saline to 352. At baseline, both groups had a similar serum bicarbonate, albumin, and base excess levels. After randomization, bicarbonate and base excess increased significantly and similarly over time (p < .0001). On multivariate analysis, fluid resuscitation with albumin predicted a smaller increase in pH (p = .0051), bicarbonate (p = .034), and base excess (p = .015). The amount of fluid was an independent predictor of pH (p < .0001), serum chloride (p < .0001), calcium (p = .0001), bicarbonate (p = .0002), and base excess (p < .0001) on the first day of treatment. In patients who received >3 L of fluids in the first 24 hrs, albumin administration was associated with a significantly greater increase in serum chloride (p = .0026). Acute Physiology and Chronic Health Evaluation II score and the presence of sepsis also independently predicted changes in several electrolytes and acid-base variables. CONCLUSIONS: When comparing albumin and saline, the choice and amount of resuscitation fluid are independent predictors of acid-base status and serum electrolytes. When large volumes are given, albumin administration leads to a higher chloride concentration. However, overall differences between the types of fluid are minor, whereas the volume of fluid administered is a much stronger predictor of such changes, which are also influenced by illness severity and the passage of time.

The incidence and outcome of septic shock patients in the absence of early-goal directed therapy.

INTRODUCTION: The purpose of the present study was to measure the incidence and outcome of septic patients presenting at the emergency department (ED) with criteria for early goal-directed therapy (EGDT). METHOD: This hospital-based, retrospective, observational study using prospectively collected electronic databases was based in a teaching hospital in Melbourne, Australia. We conducted outcome-blinded electronic screening of patients with infection admitted via the ED from 1 January 2000 to 30 June 2003. We obtained data on demographics, laboratory and clinical features on admission. We used paper records to confirm electronic identification of candidates for EGDT and to study their treatment. We followed up all patients until hospital discharge or death. RESULTS: Of 4,784 ED patients with an infectious disease diagnosis, only 50 fulfilled published clinical inclusion criteria for EGDT (EGDT candidates). Of these patients, 37 (74%) survived their hospital admission, two (4%) died in the ED, eight (16%) died in the intensive care unit and three (6%) died in the ward. After review of all ward cardiac arrests and non-NFR ('not for resuscitation') ward deaths, we identified a further two potential candidates for EGDT for an overall mortality of 28.8% (15 out of 52 patients). Analysis of treatment showed that twice as many (70%) of the EGDT candidates received vasopressor therapy in the ED, and their initial mean central venous pressure (10.8 mmHg) was almost twice that in patients from the EGDT study conducted by Rivers and coworkers. CONCLUSION: In an Australian teaching hospital candidates for EGDT were uncommon and, in the absence of an EGDT protocol, their mortality was lower than that reported with EGDT.

The effect of continuous veno-venous hemofiltration or direct hemoperfusion with polymyxin B-immobilized fiber on neutrophil respiratory oxidative burst in patients with sepsis and septic shock.

Neutrophil activates and injures tissues and organs during sepsis or septic shock. Blood purification therapies such as continuous veno-venous hemofiltration (CVVH) and direct hemoperfusion with polymyxin-immobilized fiber (PMX-DHP) have been used for the treatment of sepsis and septic shock, however, the effects of such therapies on neutrophil activation have previously been poorly understood. We sought to evaluate neutrophil reactive oxygen species (ROS), especially H2O2 production, in the pathophysiology of sepsis or septic shock and the effect of CVVH or PMX-DHP on neutrophil ROS. Seven critically ill septic patients requiring CVVH (and 12 matched septic patients who did not require CVVH as control) and seven septic shock patients treated with PMX-DHP were studied. We found that patients with sepsis or septic shock had significantly higher levels of neutrophil ROS compared with normal volunteers (183 +/- 42, 292 +/- 90, and 103 +/- 30) (P < 0.05, and < 0.005). Neutrophil ROS did not change over time in patients treated either with CVVH or without CVVH. In contrast, neutrophil ROS significantly inhibited PMX-DHP treatment in patients with septic shock (pretreatment; 292 +/- 88 vs. post-treatment; 205 +/- 93, P < 0.05). In conclusion, neutrophil ROS was significantly enhanced in the sepsis or septic shock affected patients. CVVH did not affect neutrophil ROS while PMX-DHP significant inhibited neutrophil ROS.

Myoglobin clearance by super high-flux hemofiltration in a case of severe rhabdomyolysis: a case report.

OBJECTIVE: To test the ability of a novel super high-flux (SHF) membrane with a larger pore size to clear myoglobin from serum. SETTING: The intensive care unit of a university teaching hospital. SUBJECT: A patient with serotonin syndrome complicated by severe rhabodomyolysis and oliguric acute renal failure. METHOD: Initially continuous veno-venous hemofiltration was performed at 2 l/hour ultrafiltration (UF) with a standard polysulphone 1.4 m2 membrane (cutoff point, 20 kDa), followed by continuous veno-venous hemofiltration with a SHF membrane (cutoff point, 100 kDa) at 2 l/hour UF, then at 3 l/hour UF and then at 4 l/hour UF, in an attempt to clear myoglobin. RESULTS: The myoglobin concentration in the ultrafiltrate at 2 l/hour exchange was at least five times greater with the SHF membrane than with the conventional membrane (>100,000 microg/l versus 23,003 microg/l). The sieving coefficients with the SHF membrane at 3 l/hour UF and 4 l/hour UF were 72.2% and 68.8%, respectively. The amount of myoglobin removed with the conventional membrane was 1.1 g/day compared with 4.4-5.1 g/day for the SHF membrane. The SHF membrane achieved a clearance of up to 56.4 l/day, and achieved a reduction in serum myoglobin concentration from >100,000 microg/l to 16,542 microg/l in 48 hours. CONCLUSIONS: SHF hemofiltration achieved a much greater clearance of myoglobin than conventional hemofiltration, and it may provide a potential modality for the treatment of myoglobinuric acute renal failure.

Hidden evidence to the West: multicentre, randomised, controlled trials in sepsis and systemic inflammatory response syndrome in Japanese journals.

OBJECTIVE: To assess multicentre, randomised, controlled trials (MC-RCTs) of systemic inflammatory response syndrome (SIRS) and sepsis conducted in Japan, published in Japanese and not available to English-language medical databases. DESIGN: Methodological review. SUBJECTS: All Japanese RCTs relevant to SIRS and sepsis. INTERVENTION: Identification of manuscripts using a Japanese electronic library. Critical analysis of methodology and reporting quality using a modified Methodological Quality Assessment Score and the CONSORT group check list. MEASUREMENTS AND RESULTS: Three MC-RCTs were identified. In the first, 147 patients with septic shock were randomised to methylprednisolone (1000 mg i.v.) or placebo. In the second, 221 patients were randomised to 0.20 mg/kg per h or 0.004 mg/kg per h of sivelestat for acute lung injury with SIRS. In the third, 504 patients were randomised to immunoglobulin (5 g for 3 days) or to a control group. The average methodological quality score was higher than that of equivalent Western trials. The reporting quality (CONSORT checklist) was comparable to Western studies published during the same period. CONCLUSIONS: Despite sound methodology and quality, the information obtained from relatively large Japanese critical care trials is not widely available to English-speaking investigators and therefore might be ignored in meta-analyses.

Bench-to-bedside review: treating acid-base abnormalities in the intensive care unit--the role of renal replacement therapy.

Acid-base disorders are common in critically ill patients. Metabolic acid-base disorders are particularly common in patients who require acute renal replacement therapy. In these patients, metabolic acidosis is common and multifactorial in origin. Analysis of acid-base status using the Stewart-Figge methodology shows that these patients have greater acidemia despite the presence of hypoalbuminemic alkalosis. This acidemia is mostly secondary to hyperphosphatemia, hyperlactatemia, and the accumulation of unmeasured anions. Once continuous hemofiltration is started, profound changes in acid-base status are rapidly achieved. They result in the progressive resolution of acidemia and acidosis, with a lowering of concentrations of phosphate and unmeasured anions. However, if lactate-based dialysate or replacement fluid are used, then in some patients hyperlactatemia results, which decreases the strong ion difference and induces an iatrogenic metabolic acidosis. Such hyperlactatemic acidosis is particularly marked in lactate-intolerant patients (shock with lactic acidosis and/or liver disease) and is particularly strong if high-volume hemofiltration is performed with the associated high lactate load, which overcomes the patient's metabolic capacity for lactate. In such patients, bicarbonate dialysis seems desirable. In all patients, once hemofiltration is established, it becomes the dominant force in controlling metabolic acid-base status and, in stable patients, it typically results in a degree of metabolic alkalosis. The nature and extent of these acid-base changes is governed by the intensity of plasma water exchange/dialysis and by the 'buffer' content of the replacement fluid/dialysate, with different effects depending on whether lactate, acetate, citrate, or bicarbonate is used. These effects can be achieved in any patient irrespective of whether they have acute renal failure, because of the overwhelming effect of plasma water exchange on nonvolatile acid balance. Critical care physicians must understand the nature, origin, and magnitude of alterations in acid-base status seen with acute renal failure and during continuous hemofiltration if they wish to provide their patients with safe and effective care.