方山 真朱

BACKGROUND: Altered coagulation and alveolar injury are the hallmarks of acute respiratory distress syndrome (ARDS). However, whether the biomarkers that reflect pathophysiology differ depending on the etiology of ARDS has not been examined. This study aimed to investigate the biomarker profiles of coagulopathy and alveolar epithelial injury in two subtypes of ARDS: patients with direct common risk factors (dARDS) and those with idiopathic or immune-related diseases (iARDS), which are classified as "ARDS without common risk factors" based on the Berlin definition. METHODS: This retrospective, observational study included adult patients who were admitted to the intensive care unit (ICU) at a university hospital with a diagnosis of ARDS with no indirect risk factors. Plasma biomarkers (thrombin-antithrombin complex [TAT], plasminogen activator inhibitor [PAI]-1, protein C [PC] activity, procalcitonin [PCT], surfactant protein [SP]-D, and KL-6) were routinely measured during the first 5 days of the patient's ICU stay. RESULTS: Among 138 eligible patients with ARDS, 51 were excluded based on the exclusion criteria (n = 41) or other causes of ARDS (n = 10). Of the remaining 87 patients, 56 were identified as having dARDS and 31 as having iARDS. Among the iARDS patients, TAT (marker of thrombin generation) and PAI-1 (marker of inhibited fibrinolysis) were increased, and PC activity was above normal. In contrast, PC activity was significantly decreased, and TAT or PAI-1 was present at much higher levels in dARDS compared with iARDS patients. Significant differences were also observed in PCT, SP-D, and KL-6 between patients with dARDS and iARDS. The receiver operating characteristic (ROC) analysis showed that areas under the ROC curve for PC activity, PAI-1, PCT, SP-D, and KL-6 were similarly high for distinguishing between dARDS and iARDS (PC 0.86, P = 0.33; PAI-1 0.89, P = 0.95; PCT 0.89, P = 0.66; and SP-D 0.88, P = 0.16 vs. KL-6 0.90, respectively). CONCLUSIONS: Coagulopathy and alveolar epithelial injury were observed in both patients with dARDS and with iARDS. However, their biomarker profiles were significantly different between the two groups. The different patterns of PAI-1, PC activity, SP-D, and KL-6 may help in differentiating between these ARDS subtypes.

BACKGROUND: Recent studies have suggested a low potential risk for contrast medium-induced kidney injury in patients with relatively normal renal function. However, whether contrast media cause additional deterioration of renal function in patients with acute kidney injury (AKI), including those with sepsis-associated AKI, remains unclear. This study aimed to evaluate the effect of contrast media on renal function and mortality in patients with sepsis who already had AKI. METHODS: We performed a propensity score-matched historical cohort study in the medico-surgical intensive care unit of Jichi Medical University Hospital. Adult patients who were diagnosed with sepsis and AKI were enrolled. Records from our sepsis database from 2011 to 2017 were examined. Septic patients with AKI who received contrast media within 24 h of admission (C group) were matched 1:1 with septic patients who did not receive contrast media (NC group). The primary outcome was deterioration of kidney function (DRF), which was defined as an elevation of serum creatinine levels (> 0.3 mg/dL or 1.5-fold from baseline) or induction of renal replacement therapy. RESULTS: A total of 339 septic patients with AKI were included. After propensity score adjustment, the DRF rate was similar between the C and NC groups (34.0% versus 35.0%; P = 1.00). The 7-day mortality (3.0% versus 6.0%; P = 0.50), 28-day mortality (9.2% versus 15.0%; P = 0.25), and 90-day mortality (25.8% versus 32.1%; P = 0.45) rates were comparable between the two groups. In propensity-adjusted subsets of a high-risk subset (AKI stages 2 and 3 on admission), the rate of DRF was also similar between the two groups. CONCLUSIONS: A single administration of contrast media was not associated with exacerbation of AKI or increased short/long-term mortality in patients with sepsis.

Since endothelial function is closely related to organ dysfunction in sepsis and the relationship among endothelial injury, organ dysfunction, and other biomarkers remains unclear, we aimed to evaluate the correlation among endothelial injury, organ dysfunction, and several biomarkers in patients with sepsis. Design: This was a retrospective observational study. Setting: The study was conducted in a university hospital with 14 mixed ICU beds. Patients: ICU patients with sepsis from June 2011 to December 2017 were enrolled in this study. Interventions: Endothelial biomarkers (soluble thrombomodulin, plasminogen activator inhibitor-1, and protein C) and markers of inflammation and coagulation were evaluated during the ICU stay. Sequential Organ Failure Assessment scores were assessed for 7 days after ICU admission to determine organ dysfunction. Variables were compared among five stratified groups according to the Sequential Organ Failure Assessment score (0-2, 3-5, 6-8, 9-12, and 13-24). Regression analysis and 95% CIs were used to evaluate trends in biomarkers. Measurements and Main Results: The patients were divided into five stratified groups (Sequential Organ Failure Assessment 0-2, n = 159 [20.5%]; Sequential Organ Failure Assessment 3-5, n = 296 [38.2%]; Sequential Organ Failure Assessment 6-8, n = 182 [23.5%]; Sequential Organ Failure Assessment 9-12, n = 75 [9.7%]; Sequential Organ Failure Assessment 13-24, n = 31 [4.0%]). Protein C activity was significantly correlated with the severity of organ dysfunction. It was lower on day 1, increased upon successful treatment, and was significantly higher in groups with lower Sequential Organ Failure Assessment scores. Conclusions: Trends and activity of protein C were superior in predicting organ dysfunction compared with other endothelial biomarkers. Monitoring the level of protein C activity is an ideal tool to monitor organ dysfunctions in patients with sepsis.

Background: Intravenous glycerol treatment, usually administered in the form of a 5% fructose solution, can be used to reduce intracranial pressure. The administered fructose theoretically influences blood lactate levels, although little is known regarding whether intravenous glycerol treatment causes transient hyperlactatemia. This study aimed to evaluate blood lactate levels in patients who received intravenous glycerol or mannitol. Methods: This single-center prospective observational study was performed at a 14-bed general intensive care unit between August 2016 and January 2018. Patients were excluded if they were < 20 years old or had pre-existing hyperlactatemia (blood lactate > 2.0 mmol/L). The included patients received intravenous glycerol or mannitol to reduce intracranial pressure and provided blood samples for lactate testing before and after the drug infusion (before the infusion and after 15 min, 30 min, 45 min, 60 min, 90 min, 120 min, and 150 min). Results: Among the 33 included patients, 13 patients received 200 mL of glycerol over 30 min, 13 patients received 200 mL of glycerol over 60 min, and 7 patients received 300 mL of mannitol over 60 min. Both groups of patients who received glycerol had significantly higher lactate levels than the mannitol group (2.8 mmol/L vs. 2.2 mmol/L vs. 1.6 mmol/L, P < 0.0001), with the magnitude of the increase in lactate levels corresponding to the glycerol infusion time. There were no significant inter-group differences in cardiac index, stroke volume, or stroke volume variation. In the group that received the 30-min glycerol infusion, blood lactate levels did not return to the normal range until after 120 min. Conclusions: Intravenous administration of glycerol leads to higher blood lactate levels that persist for up to 120 min. Although hyperlactatemia is an essential indicator of sepsis and/or impaired tissue perfusion, physicians should be aware of this phenomenon when assessing the blood lactate levels.

症例は66歳男性で、5日前から全身倦怠感ならびに感冒症状を認めた。1日前から呼吸困難感が出現し、SpO2が90%、胸部X線では両側肺野に浸潤陰影、胸部CTでは両側中下肺野にすりガラス陰影を認めた。間質性肺疾患の疑いで入院し、酸素療法と第3世代セフェム投与を開始した。しかし、呼吸困難感は徐々に進行した。翌日、気管挿管・人工呼吸を開始したが、左気胸が出現したため胸腔ドレーン留置後に救急搬送となった。徒手換気下で胸部CTを行ったところ、広範な荷重側無気肺を形成しており気管支牽引像を認めなかった。間質性肺疾患よりも細菌性肺炎による敗血症性ARDSを疑った。画像所見から肺胞リクルートメントが有効と判断し、腹臥位療法とAPRVを併用したopen lung strategyを施行した。レボフロキサシンを開始し、メチルプレドニゾロンを3日間投与した。第8病日に抜管し、第21病日には酸素投与なしで退院した。

当ICUにおけるHAMILTON-G5 INTELLiVENT-ASV(Int/ASV)の使用経験について報告した。2013年7月〜2014年1月迄にInt/ASVは頭頸部ならびに腹部予定手術後患者15例で使用され、平均年齢は55歳、男性が50%、APACHE IIは平均4.4であった。人工呼吸期間は平均3日間で、従来の方法と差はみられなかった。人工呼吸器に関連する有害事象は認めなかったが、2例でパルスオキシメーターやカプノグラフからのデータ取得の問題から導入できなかった。今回の結果から術後症例での使用は可能と判断した。Quick Wean機能やSBTは使用したものの効果判定には至らなかったが、問題なく使用できた。一方、一回換気量が小さく呼吸回数が低下しない拘束性肺障害患者や重症呼吸不全患者では、適応や安全性について今後さらなる評価が必要と考えられた。

ジスチグミン臭化物10 mg/dayを1年間にわたり内服し，3ヶ月以上続く難治性の下痢や嘔吐など消化器症状のため入院したが，ジスチグミン臭化物中毒によるコリン作動性クリーゼを発症し，救命し得なかった一症例を経験した。背景に肝硬変があり，慢性的にコリンエステラーゼ値が低値であったため，ジスチグミン臭化物中毒の診断に時間がかかった。コリンエステラーゼ残存率は約7ヶ月前から異常低値であり，難治性の消化器症状が出現した時期と合わせて慢性中毒と考えた。難治性の消化器症状およびコリンエステラーゼ値が異常低値を示す高齢者では，ジスチグミン臭化物の中毒を疑い，早期から集中治療の対象とするのが望ましい。