吉永 晃一

OBJECTIVE: Systemic heparinization during cardiopulmonary bypass (CPB) can significantly affect thromboelastography (TEG). This study investigated the feasibility of adding protamine in vitro to allow assessment of coagulation status using the TEG 6s system during CPB. METHODS: In this prospective observational study, 21 patients undergoing elective cardiac valve surgery were evaluated. During CPB, protamine was added in vitro to the heparinized blood of these patients at a concentration of 0.05 mg/mL and analyzed with the TEG 6s (Pre). The TEG parameters were compared to those analyzed after CPB withdrawal and systemic protamine administration (Post). RESULTS: The citrated kaolin maximal amplitude (CK-MA) and the citrated functional fibrinogen maximal amplitude (CFF-MA) exhibited strong correlations between Pre and Post measurements (r = 0.790 and 0.974, respectively, P < 0.001 for both), despite significant mean differences (-2.23 mm for CK-MA and -0.68 mm for CFF-MA). Bland-Altman analysis showed a clinically acceptable agreement between Pre and Post measurement of CK-MA and CFF-MA (the percentage error was 10.6% and 12.2%, respectively). In contrast, the citrated kaolin reaction time (CK-R) showed no significant correlation between Pre and Post measurements (r = 0.328, P = 0.146), with a mean difference of 1.42 min (95% CI: -0.45 to 3.29). CONCLUSIONS: In vitro protamine addition allows assessment of coagulation status during CPB using the TEG 6s system. CK-MA and CFF-MA measured during CPB using this method revealed a strong correlation and agreement with post-CPB measurements, suggesting that our method potentially facilitates early prediction of post-CPB coagulation status and decision-making on transfusion strategies. CLINICAL TRIAL REGISTRATION: The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR, registration number: UMIN000041097, date of registration: July 13, 2020, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046925 ) before the recruitment of participants.

BACKGROUND: Tracking preload dependency non-invasively to maintain adequate tissue perfusion in the perioperative period can be challenging.The effect of phenylephrine on stroke volume is dependent upon preload. Changes in stroke volume induced by phenylephrine administration can be used to predict preload dependency. The change in the peripheral perfusion index derived from photoplethysmography signals reportedly corresponds with changes in stroke volume in situations such as body position changes in the operating room. Thus, the peripheral perfusion index can be used as a non-invasive potential alternative to stroke volume to predict preload dependency. Herein, we aimed to determine whether changes in perfusion index induced by the administration of phenylephrine could be used to predict preload dependency. METHODS: We conducted a prospective single-centre observational study. The haemodynamic parameters and perfusion index were recorded before and 1 and 2 min after administering 0.1 mg of phenylephrine during post-induction hypotension in patients scheduled to undergo surgery. Preload dependency was defined as a stroke volume variation of ≥ 12% before phenylephrine administration at a mean arterial pressure of < 65 mmHg. Patients were divided into four groups according to total peripheral resistance and preload dependency. RESULTS: Forty-two patients were included in this study. The stroke volume in patients with preload dependency (n = 23) increased after phenylephrine administration. However, phenylephrine administration did not impact the stroke volume in patients without preload dependency (n = 19). The perfusion index decreased regardless of preload dependency. The changes in the perfusion index after phenylephrine administration exhibited low accuracy for predicting preload dependency. Based on subgroup analysis, patients with high total peripheral resistance tended to exhibit increased stroke volume following phenylephrine administration, which was particularly prominent in patients with high total peripheral resistance and preload dependency. CONCLUSION: The findings of the current study revealed that changes in the perfusion index induced by administering 0.1 mg of phenylephrine could not predict preload dependency. This may be attributed to the different phenylephrine-induced stroke volume patterns observed in patients according to the degree of total peripheral resistance and preload dependency. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN000049994 on 9/01/2023).

BACKGROUND: It has been 50 years since the pulmonary artery catheter was introduced, but the actual use of pulmonary artery catheters in recent years is unknown. Some randomized controlled trials have reported no causality with mortality, but some observational studies have been published showing an association with mortality for patients with cardiogenic shock, and the association with a pulmonary artery catheter and mortality is unknown. The aim of this study was to investigate the utilization of pulmonary artery catheters (PACs) in the intensive care unit (ICU) and to examine their association with mortality, taking into account differences between hospitals. METHODS: This is a retrospective analysis using the Japanese Intensive care PAtient Database, a multicenter, prospective, observational registry in Japanese ICUs. We included patients aged 16 years or older who were admitted to the ICU for reasons other than procedures. We excluded patients who were discharged within 24 h or had missing values. We compared the prognosis of patients with and without PAC. The primary outcome was hospital mortality. We performed propensity score analysis to adjust for baseline characteristics and hospital characteristics. RESULTS: Among 184,705 patients in this registry from April 2015 to December 2020, 59,922 patients were included in the analysis. Most patients (94.0%) with a PAC in place had cardiovascular disease. There was a wide variation in the frequency of PAC use between hospitals, from 0 to 60.3% (median 14.4%, interquartile range 2.2-28.6%). Hospital mortality was not significantly different between the PAC use group and the non-PAC use group in patients after adjustment for propensity score analysis (3.9% vs 4.3%; difference, - 0.4%; 95% CI - 1.1 to 0.3; p = 0.32). Among patients with cardiac disease, those with post-open-heart surgery and those in shock, hospital mortality was also not significantly different between the two groups (3.4% vs 3.7%, p = 0.45, 1.7% vs 1.7%, p = 0.93, 4.8% vs 4.9%, p = 0.87). CONCLUSIONS: The frequency of PAC use varied among hospitals. PAC use for ICU patients was not associated with lower hospital mortality after adjusting for differences between hospitals.

BACKGROUND: The incidence of delirium is high in older patients undergoing cardiovascular surgery with cardiopulmonary bypass (CPB). Intraoperative tissue hypoperfusion and re-reperfusion injury, which generate reactive oxygen species (ROS), are suggested to induce delirium. Ascorbic acid is an excellent antioxidant and may reduce organ damage by inhibiting the production of ROS. This prospective observational study aimed to measure pre- and postoperative plasma ascorbic acid levels and examine their association with delirium. METHODS: Patients older than 70 years of age scheduled for elective cardiovascular surgery using CPB were enrolled. From September 2020 to December 2021, we enrolled 100 patients, and the data of 98 patients were analyzed. RESULTS: In total, 31 patients developed delirium, while 67 did not. Preoperative plasma ascorbic acid levels did not differ between the non-delirium and delirium groups (6.0 ± 2.2 vs. 5.5 ± 2.4 µg/mL, p = 0.3). Postoperative plasma ascorbic acid levels were significantly different between the groups (2.8 [2.3-3.5] vs. 2.3 [1.6-3.3] µg/mL, p = 0.037). CONCLUSIONS: In patients who undergo cardiovascular surgery with CPB, lower postoperative plasma ascorbic acid levels may be associated with the development of delirium.

BACKGROUND: Capillary refill time (CRT) is the gold standard for evaluating peripheral organ perfusion; however, intraoperative CRT measurement is rarely used because it cannot be conducted continuously, and it is difficult to perform during general anesthesia. The peripheral perfusion index (PI) is another noninvasive method for evaluating peripheral perfusion. The PI can easily and continuously evaluate peripheral perfusion and could be an alternative to CRT for use during general anesthesia. This study aimed to determine the cutoff PI value for low peripheral perfusion status (prolonged CRT) by exploring the relationship between CRT and the PI during general anesthesia. METHODS: We enrolled 127 surgical patients. CRT and the PI were measured in a hemodynamically stable state during general anesthesia. A CRT >3 s indicated a low perfusion status. RESULTS: Prolonged CRT was observed in 27 patients. The median PI values in the non-prolonged and prolonged CRT groups were 5.0 (3.3-7.9) and 1.5 (1.2-1.9), respectively. There was a strong negative correlation between the PI and CRT (r = -0.706). The area under the receiver operating characteristic curve generated for the PI was 0.989 (95% confidence interval, 0.976-1.0). The cutoff PI value for detecting a prolonged CRT was 1.8. CONCLUSION: A PI <1.8 could accurately predict a low perfusion status during general anesthesia in the operating room. A PI <1.8 could be used to alert the possibility of a low perfusion status in the operating room. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN000043707; retrospectively registered on March 22, 2021, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno = R000049905).

Background: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. Methods: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. Results: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4–8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D); we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D); we suggest against routinely implementing NO inhalation therapy (GRADE 2C); and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). Conclusions: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jrs.or.jp/publication/jrs_guidelines/). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

After publication of the original article, the authors selfverified their study protocol and determined that their clinical trial was registered after the study was initiated. Therefore the authors would like to clarify that the registration in the University hospital Medical Information Network (UMIN000040159) was retrospective.

INTRODUCTION: The end-expiratory occlusion test (EEOT) may predict the response to fluid administration in patients undergoing lung-protective ventilation, but arterial catheter insertion is necessary to evaluate changes in stroke volume (SV). The peripheral perfusion index is a potential noninvasive alternative to evaluate SV. The aim of this study is to investigate whether changes in perfusion index during an intraoperative EEOT can predict the response to fluid administration in patients undergoing lung-protective ventilation (tidal volume 7 ml/kg predicted body weight). METHODS: Forty-one elective surgical patients were enrolled. The SV and perfusion index were recorded before (baseline), during a 40-s EEOT and after volume expansion (250 ml of lactated Ringer's solution over 10 min). Patients with an increase in SV greater than 10% after volume expansion were defined as responders. ΔPI (change in perfusion index between baseline and 20 (ΔPI20) or 40 s (ΔPI40) after the beginning of EEOT were calculated using: ΔPI20 (%) = [(PI at 20 s after EEOT beginning - PIbaseline)/PIbaseline] × 100, ΔPI40 (%) = [(PI at 40 s after EEO beginning - PIbaseline)/PIbaseline] × 100). RESULTS: Sixteen patients were responders, and 25 were non-responders. The area under the receiver operating characteristics curves generated for ΔPI20 and ΔPI40 to predict response to a fluid challenge were 0.561 (95% CI 0.374-0.749) and 0.688 (95% CI 0.523-0.852), respectively. CONCLUSION: Changes in perfusion index during intraoperative EEOT in patients undergoing lung-protective ventilation (7 ml/kg) were unable to predict the response to fluid administration.

<title>Abstract</title><sec> <title>Background</title> Anticoagulation management of patients with antiphospholipid syndrome (APS) undergoing cardiac surgery is challenging due to the prolongation of activated clotting time (ACT). Currently, no study has compared the utility of ACT monitoring using the Hemochron Jr. Signature+ and that of heparin concentration management using the Hemostasis Management System (HMS) Plus in patients with APS. </sec><sec> <title>Case presentation</title> A 71-year-old woman with APS was scheduled to undergo an aortic valve replacement for aortic regurgitation. The ACT was measured using the Hemochron Jr. Signature+, and the heparin concentration was measured concurrently using the HMS Plus. ACT over 480 s corresponded to an adequate heparin concentration during cardiopulmonary bypass. The clinical course was uneventful, and no thrombotic or hemorrhagic complications were observed. </sec><sec> <title>Conclusion</title> In the present patient with APS, the Hemochron Jr. Signature+ was useful as an anticoagulation management during cardiac valve surgery. </sec>

piRNA (PIWI-interacting RNA) is a germ cell-specific small RNA in which biogenesis PIWI (P-element wimpy testis) family proteins play crucial roles. MILI (mouse Piwi-like), one of the three mouse PIWI family members, is indispensable for piRNA production, DNA methylation of retrotransposons presumably through the piRNA, and spermatogenesis. The biogenesis of piRNA has been divided into primary and secondary processing pathways; in both of these MILI is involved in mice. To analyze the molecular function of MILI in piRNA biogenesis, we utilized germline stem (GS) cells, which are derived from testicular stem cells and possess a spermatogonial phenotype. We established MILI-null GS cell lines and their revertant, MILI-rescued GS cells, by introducing the Mili gene with Sendai virus vector. Comparison of wild-type, MILI-null, and MILI-rescued GS cells revealed that GS cells were quite useful for analyzing the molecular mechanisms of piRNA production, especially the primary processing pathway. We found that glycerol-3-phosphate acyltransferase 2 (GPAT2), a mitochondrial outer membrane protein for lysophosphatidic acid, bound to MILI using the cells and that gene knockdown of GPAT2 brought about impaired piRNA production in GS cells. GPAT2 is not only one of the MILI bound proteins but also a protein essential for primary piRNA biogenesis. Copyright © 2013 RNA Society.