Kazui Soma

Efficacy of Continuous Regional Arterial Infusion of a Protease Inhibitor and Antibiotic for Severe Acute Pancreatitis in Patients Admitted to an Intensive Care Unit

Abstract: To investigate the efficacy of continuous regional arterial infusion (CRAI) of a protease inhibitor and antibiotic for severe acute pancreatitis (SAP) in patients admitted to an intensive care unit (ICU). A total of 51 patients with SAP requiring admission to an ICU were studied. The patients were divided into two groups: one received the protease inhibitor nafamostat mesylate and the antibiotic imipenem by continuous regional arterial infusion (CRAI group) and the other received protease inhibitors and antibiotics by intravenous infusion (non-CRAI group). To evaluate the therapeutic usefulness of CRAI of a protease inhibitor and antibiotic for SAP, the rate of surgery and the cumulative survival rate were compared between the non-CRAI group and the CRAI group. The rate of surgery was 32% in the non-CRAI group and 9% in the CRAI group (P = 0.08). Cumulative survival rates at 1, 6, and 12 months were 77.9%, 48.9%, and 48.9% in the non-CRAI group compared with 100.0%, 100.0%, and 87.1% in the CRAI group. Outcome was thus significantly better in the CRAI group than in the non-CRAI group (P = 0.002). CRAI of a protease inhibitor and antibiotic may decrease the need for surgical therapy and reduce mortality in patients with SAP.

Iliac vein injuries in hemodynamically unstable patients with pelvic fracture caused by blunt trauma.

BACKGROUND Major pelvic venous injuries secondary to blunt trauma can be a difficult problem in diagnosis and management. This study aimed to elucidate the clinical significance of iliac vein injuries demonstrated by venography in patients with blunt pelvic injuries who remained unstable even after transcatheter arterial embolization (TAE). METHODS We reviewed the records of 72 patients with unstable pelvic fracture who presented with shock at our center after blunt trauma from 1999 through 2003. The average Injury Severity Score was 34.3 in this study population. RESULTS TAE was the first method of choice to control bleeding from pelvic fracture in 61 patients. Thirty-six patients recovered from shock after TAE. Eighteen of 25 who did not recover from shock died. In 11 of these 25, transfemoral venography with a balloon catheter was performed, revealing significant venous extravasation in 9: common iliac vein in 5, internal iliac vein in 3, and external iliac vein in 1. The average Injury Severity Score of patients with iliac vein injury was 45.8. Treatments for venous injuries were laparotomy for hemostasis (n = 1, survivors = 0), retroperitoneal gauze packing (n = 3, survivors = 1), and endovascular stent placement (n = 3, survivors = 3). Two patients suffered from cardiac arrest before treatment for venous injury. External fixations were performed after TAE according to fracture type. CONCLUSION The iliac vein injury is the principal cause of hemorrhagic shock in some patients with unstable pelvic fractures after blunt trauma. Venography is useful for identifying iliac vein injuries.

Management of Unruptured Intracranial Aneurysm in Japan A Markovian Decision Analysis with Utility Measurements Based on the Glasgow Outcome Scale

The purpose of this study was to analyze the management of individual patients with unruptured intracranial aneurysms (UN-ANs) using a decision-analytic approach. Tran sition probabilities among Glasgow Outcome Scale (GOS) categories were estimated from the published literature and data from patients who had been treated at Kitasato University Hospital. Utilities were obtained from 140 health providers based principally on the GOS. Baseline analysis for a healthy 40-year-old man with an anterior UN-AN less than 10 mm in diameter showed that the quality-adjusted life expectancies for preventive operation and follow-up were 15.34 and 14.66 years, respectively. For a follow-up strategy to be preferred, the annual rupture rate had to be as low as 0.9%. These results were sustained through extensive sensitivity analysis. The results sup port preventive operation for UN-ANs, and identify problems that can be clarified with a well-designed stratified clinical trial. Key words: decision analysis; Markov model; unruptured intracranial aneurysms; Glasgow Outcome Scale; utility; preventive oper ations. (Med Decis Making 1998;18:357-364)

Miniprobe ultrasonography for determining prognosis in corrosive esophagitis

OBJECTIVE:We evaluated the ability of endoscopic ultrasonography to predict likelihood of stricture formation in patients with corrosive esophagitis.METHODS:Consecutive patients with esophagitis resulting from alkaline or acid chemical ingestion (n = 11) were evaluated prospectively by endoscopic ultrasonography between hospital days 4 and 12. Findings for the most severe lesion were classified according to the appearance of the muscular layers: distinct muscular layers without thickening (grade 0); distinct muscular layers with thickening (grade I); obscured muscular layers with indistinct margins (grade II); and muscular layers that could not be differentiated (grade III). Findings were also classified according to whether apparent damage to muscular layers in the worst-appearing image involved part of the circumference (type a) or the whole circumference (type b). Implications of these findings for subsequent stricture formation were then evaluated.RESULTS:Stricture formation did not occur in patients with grade 0 or grade I images; transient stricture formation occurred in a patient showing grade IIa. Stricture requiring repeated bougie dilation occurred in a patient showing grade IIIb.CONCLUSIONS:Endoscopic ultrasonographic images presumed to reflect the destruction of muscular layers (grades II to III), as opposed to only edema (grade I), may be associated with stricture formation. This modality can accurately visualize deep lesions in corrosive esophagitis, making it prognostically useful.

Massive Noninflammatory Periportal Liver Necrosis Following Concentrated Acetic Acid Ingestion

In a fatal occurrence of massive liver necrosis following ingestion of concentrated (90%) acetic acid, the patient showed evidence of hemolysis, disseminated intravascular coagulation, and liver dysfunction at only 45 minutes after exposure. With refractory to vigorous supportive care, the patient s condition deteriorated until death occurred 39 hours after ingestion, despite some improvement of coagulopathy. Autopsy revealed corrosive injuries in the upper gastrointestinal tract and massive hepatic necrosis in a periportal distribution without significant inflammation. A direct effect of the noxious agent on hepatocytes involving the portal circulation is suggested.

Elevated S100B level in cerebrospinal fluid could predict poor outcome of carbon monoxide poisoning

OBJECTIVE S100B is a calcium-binding protein produced by astroglia in the brain and has been used as a marker of neuronal damage after brain trauma. We investigated the utility of S100B in cerebrospinal fluid (CSF) measured during the early phase of carbon monoxide (CO) poisoning in predicting the subsequent clinical course. METHODS The study included 31 patients who were admitted to the hospital with loss of consciousness following CO poisoning. S100B levels were measured by enzyme-linked immunosorbent assay in CSF, and serum samples collected simultaneously within 24 hours and on the fourth day after CO exposure. All patients were followed for at least 3 months and divided into 3 groups based on the clinical course: persistent vegetative state (PVS), delayed encephalopathy (DE), and complete recovery with no complications (NC). RESULTS During the 3-month period, 3 patients developed PVS, 5 developed DE, and 23 were classified as NC. The mean S100B levels in the CSF within 24 hours after CO exposure were higher in the PVS group (9.25 ng/mL) than in the DE (2.03 ng/mL) and NC groups (1.86 ng/mL). However, the mean serum S100B levels were not elevated in the 3 groups (0.21, 0.59, and 0.16 ng/mL, respectively). CONCLUSION Early elevation of S100B in CSF after CO poisoning could be a suitable predictor of subsequent development of PVS.

Reanalysis of unruptured intracranial aneurysm management: effect of a new international study on the threshold probabilities.

Objective. This report updates previous clinical decision analysis for patients with unruptured intracranial aneurysm (UN-AN) based on newly published data and discusses the role of reanalysis in individual decision making. Methods. The authors employed probabilities for the natural history of UN-AN and results of preventive surgery based on the report by the International Study of Unruptured Intracranial Aneurysms. Probabilistic sensitivity analysis with Monte Carlo simulation and traditional n-way sensitivity analyses were used to assess the uncertainty of clinical decisions. Results. The baseline decision in favor of preventive surgery is reversed by new data from the international study. Probabilistic sensitivity analyses revealed several populations showing heterogeneity in terms of strategy selection. One- and two-way sensitivity analyses detected two important factors for decision making: annual rupture rate and utility for knowingly living with UN-AN. Conclusions. Annual UN-AN rupture rate and the utility for knowingly living with UN-AN are key factors when deciding on a therapeutic strategy. Also, updating published decision analyses can improve clinical decision making by integrating clinical judgment and newly available clinical data.

Blockade of bradykinin B2 receptor suppresses acute pancreatitis induced by obstruction of the pancreaticobiliary duct in rats

The involvement of bradykinin (BK) B2 receptor in acute pancreatitis induced by pancreaticobiliary duct ligation was investigated in rats. The activities of amylase and lipase in the serum, the water content of the pancreas, and vacuolization of the acinar cells were significantly increased 2 h after obstruction of the duct in Sprague‐Dawley rats. Elevated serum amylase activity, increased pancreatic oedema, and damage of the pancreatic tissue were significantly less marked in plasma kininogen‐deficient, B/N‐Katholiek rats than in the normal strain, B/N‐Kitasato rats 2 h after the ligation. Obstruction of the pancreaticobiliary duct augmented the level of (1‐5)‐BK (Arg1‐Pro2‐Pro3‐Gly4‐Phe5), a stable BK metabolite, in the blood from 73.0±21.7 pg ml−1 at 0 h to 149.8±38.0 pg ml−1 at 2 h after the induction of pancreatitis in SD rats. Administration of a BK B2 receptor antagonist, FR173657 (100 mg kg−1, p.o.) or Hoe140 (100 nmol kg−1, s.c.), reduced the elevation of amylase and lipase activities in the serum and of pancreatic water content in a dose‐dependent manner. The effective attenuation of oedema formation and vacuolization by the antagonists was also confirmed light‐microscopically. In contrast, treatment with gabexate mesilate or indomethacin did not cause significant suppression of the pancreatitis. These findings suggest a possible involvement of kinin B2 receptor in the present pancreatitis model. Furthermore, they point to the potential usefulness of the B2 receptor in clinical acute pancreatitis.

Effect of neutral endopeptidase inhibitor on bradykinin-induced bronchoconstriction

To evaluate whether neutral endopeptidase (NEP) inhibitors have adverse respiratory effects, the influence of a NEP inhibitor on bradykinin (BK)-induced bronchoconstriction was investigated. In anesthetized and artificially ventilated guinea pigs, changes in airway opening pressure (Pao) were measured as an index of bronchoconstriction. An infusion of phosphoramidon (3 mg kg(-1) h(-1)), a NEP inhibitor, significantly enhanced the bronchoconstriction induced by high-dose BK (30 nmol kg(-1), i.v.). Capsaicin (0.1 mg kg(-1), i.v.) and SR48968 (0.3 mg kg(-1), i.v.), an NK2 receptor antagonist, significantly inhibited the phosphoramidon-induced enhancement of BK-induced bronchoconstriction, although FK888 (3 mg kg(-1), i.v.), an NK1 receptor antagonist, did not. Both neurokinin A (NKA) (0.1-3 nmol kg(-1), i.v.) and substance P (SP) (0.1-3 nmol kg(-1), i.v.) induced dose-dependent bronchoconstriction which was enhanced by phosphoramidon infusion, although these enhancements were more prominent in the NKA series. Phosphoramidon partially inhibited BK degradation in lung homogenate, and both NKA and SP degradation in the lung homogenate were significantly suppressed by phosphoramidon. In bronchoalveolar lavage fluid (BALF), levels of NKA and SP were significantly elevated after a bolus of BK with a phosphoramidon infusion. These results suggest that NEP inhibitors may have adverse respiratory effects resulting from inhibition of the degradation of neurokinins, but mainly of NKA, when a large amount of BK is generated.

Impact of Platelet Transfusion on Survival of Patients with Intracerebral Hemorrhage after Administration of Anti-Platelet Agents at a Tertiary Emergency Center

This study examined the impact of platelet transfusion (PLT) on the survival of intracerebral hemorrhage (ICH) patients who had been administered anti-platelet agents (APA). This retrospective cohort analysis investigated 432 patients (259 men, 60%) who were newly diagnosed with ICH between January 2006 and June 2011 at the tertiary emergency center of Kitasato University Hospital. Median age on arrival was 67.0 years (range, 40–95 years). ICH was subcortical in 72 patients (16.7%), supratentorial in 233 (53.9%), and infratentorial in 133 (30.8%). PLT was performed in 16 patients (3.7%). Within 90 days after admission to the center, 178 patients (41.2%) had died due to ICH. Before the onset of ICH, 66 patients had been prescribed APA because of atherosclerotic diseases. Multivariate regression analysis indicated APA administration was an independent risk factor for death within 7 days (odds ratio, 5.12; P = 0.006) and within 90 days (hazard ratio, 1.87; P = 0.006) after arrival. Regarding the effect of a PLT in ICH patients with APA, no patient with PLT died. PLT had a survival benefit on patients with ICH, according to our analysis. Further prospective analysis is necessary to confirm the effects of PLT on survival in ICH with APA.