Post-intensive care syndrome (PICS) affects the quality of life (QOL) of survivors of critical illness. Although PICS persists for a long time, the longitudinal changes in each component and their interrelationships over time both remain unclear. This multicenter prospective study investigated the 2-year trajectory of PICS and its components as well as factors contributing to deterioration or recovery in mechanically ventilated patients with coronavirus disease 2019 (COVID-19), and also attempted to identify possible countermeasures. Patients who survived COVID-19 requiring mechanical ventilation completed questionnaires on the Barthel index, Short-Memory Questionnaire, Hospital Anxiety and Depression Scale, and EuroQol 5 dimensions 5-level every six months over a two-year period. Scores were weighted to account for dropouts, and the trajectory of each functional impairment was evaluated with alluvial diagrams. The prevalence of PICS and factors impairing or restoring function were examined using generalized estimating equations considering trajectories. Among 334 patients, PICS prevalence rates in the four completed questionnaires were 72.1, 78.5, 77.6, and 82.0

Objective To implement early rehabilitation interventions by physical therapists is recommended. However, the effectiveness of early rehabilitation for severe coronavirus disease 2019 (COVID-19) patients in the prevention of post-intensive care syndrome (PICS) is unclear. We analyzed a multicenter prospective observational study (Post-Intensive Care outcomeS in patients with COronaVIrus Disease 2019) to examine the association between early rehabilitation interventions and PICS physical impairment. Methods An analysis was performed on COVID-19 patients who were admitted to intensive care units (ICUs) between March 2020 and March 2021, and required mechanical ventilation. The primary outcome was the incidence of PICS physical impairment (Barthel Index≤90) after one year. Multivariate logistic regression analysis was used to estimate the association between early rehabilitation interventions and PICS physical impairment by adjusting ICU mobility scale (IMS) during seven-day following ICU admission, and clinically relevant risk factors. Results The analysis included 259 patients, 54 of whom developed PICS physical impairment one year later. In 81 patients, physical therapists intervened within seven days of ICU admission. There was no significant difference in mean IMS by day seven of admission between the early and non-early rehabilitation patients (0.70 and 0.61, respectively). Multivariate logistic regression analysis showed that early rehabilitation interventions were significantly associated with a low incidence of PICS physical impairment (odds ratio, 0.294; 95% confidence interval, 0.123–0.706; p=0.006). Conclusion Early rehabilitation interventions by physical therapists were an independent factor associated with the decreased development of PICS physical impairment at one year, even though early rehabilitation had no significant effect on IMS.

To ensure good outcomes in patients presenting with vertigo, accurate prediction ruling out central vertigo is crucial during initial assessment. This study was conducted to develop a clinical decision rule (CDR) using objectively measurable predictors to exclude central vertigo, while maintaining 100% sensitivity. This was a multicenter, prospective, cohort study analyzing patients presenting to the emergency departments of six hospitals in Japan from April 2011 to March 2014. Eligible patients were 3,001 patients aged > 15 years. Patients were excluded if they presented with trauma, intoxication, heatstroke, anaphylaxis, or unconsciousness. The main outcome measure, definitive diagnosis of central vertigo, was based on confirmation of intracranial bleeding on head computed tomography (CT) or cerebral or cerebellar infarction or tumor on brain magnetic resonance imaging (MRI). Univariate analysis and multivariate recursive partitioning analysis were performed. A total of 1,938 patients were enrolled. Of 1,133 cases, 60 were diagnosed with central vertigo. The CDR diagnosed central vertigo if any of the following were present: headache or neck pain, vomiting, sBP > 150 mmHg, BS > 140 mg/dL, or LDH > 230 IU/L, providing sensitivity of 100% (95% CI 94.0-100%) and specificity of 21.2% (95% CI: 18.9-23.7%) to exclude central vertigo. The rule was validated in 805 eligible patients, of whom 87 had central vertigo, demonstrating sensitivity of 100% (95% CI: 95.8-100%) and specificity of 20.0% (95% CI: 17.4-22.9%). A highly sensitive CDR to exclude central vertigo was developed for patients presenting with vertigo to emergency departments. Further verification is needed to generalize this CDR.

The aim of this study was to evaluate whether frailty was associated with 6-month mortality in older adults who were admitted to the intensive care unit (ICU) with an illness requiring emergency care. The investigation was a prospective, multi-center, observational study conducted among the ICUs of 17 participating hospitals. Patients ≥ 65 years of age who were admitted to the ICU directly from an emergency department visit were assessed to determine their baseline Clinical Frailty Scale (CFS) scores before the illness and were surveyed 6 months after admission. Among 650 patients included in the study, the median age was 79 years old, and overall mortality at 6 months was as low as 21%, ranging from 6.2% in patients with CFS 1 to 42.9% in patients with CFS ≥ 7. When adjusted for potential confounders, CFS score was an independent prognostic factor for mortality (one-point increase in CFS, adjusted risk ratio with 95% confidence interval 1.19 [1.09–1.30]). Quality of life 6 months after admission worsened as baseline CFS score increased. However, there was no association between total hospitalization cost and baseline CFS. CFS is an important predictor of long-term outcomes among critically ill older patients requiring emergent admission.

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1-5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.

Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.

Introduction: Post-intensive care syndrome (PICS) is an emerging problem in critically ill patients and the prevalence and risk factors are unclear in patients with severe coronavirus disease 2019 (COVID-19). This multicenter prospective observational study aimed to investigate the prevalence and risk factors of PICS in ventilated patients with COVID-19 after ICU discharge. Methods: Questionnaires were administered twice in surviving patients with COVID-19 who had required mechanical ventilation, concerning Barthel Index, Short-Memory Questionnaire, and Hospital Anxiety and Depression Scale scores. The risk factors for PICS were examined using a multivariate logistic regression analysis. Results: The first and second PICS surveys were obtained at 5.5 and 13.5 months (mean) after ICU discharge, with 251 and 209 patients completing the questionnaires and with a prevalence of PICS of 58.6% and 60.8%, respectively, along with the highest percentages of cognitive impairment. Delirium (with an odds ratio of (OR) 2.34, 95% CI 1.1–4.9, and p = 0.03) and the duration of mechanical ventilation (with an OR of 1.29, 95% CI 1.05–1.58, and p = 0.02) were independently identified as the risk factors for PICS in the first PICS survey. Conclusion: Approximately 60% of the ventilated patients with COVID-19 experienced persistent PICS, especially delirium, and required longer mechanical ventilation.

Abstract Aims/Introduction The aim of the present study was to clarify the pathophysiologies of hyperglycemic crises in Japanese patients. Materials and Methods This was a retrospective study of patients with hyperglycemic crises admitted to Kumamoto Medical Center, Kumamoto, Japan, between 2012 and 2019. Patients were classified as having diabetic ketoacidosis (DKA), hyperglycemic hyperosmotic syndrome (HHS) or a mixed state of the two conditions (MIX), and laboratory data and levels of consciousness at hospital admission, as well as the rates of mortality and coagulation disorders, were compared. Results The diagnostic criteria for hyperglycemic crisis were met in 144 cases, comprising 87 (60.4%), 38 (26.4%) and 19 (13.2%) cases of DKA, HHS and MIX, respectively. Type 1 diabetes was noted in 46.0 and 26.3% of patients in the DKA and MIX groups, respectively. Fibrin degradation product and D‐dimer levels were significantly higher in the HHS group than in the DKA group (DKA and HHS groups: fibrin degradation product 7.94 ± 8.43 and 35.54 ± 51.80 μg/mL, respectively, P < 0.01; D‐dimer 2.830 ± 2.745 and 14.846 ± 21.430 μg/mL, respectively, P < 0.01). Mortality rates were 5.7, 13.2 and 5.3% in the DKA, HHS and MIX groups, respectively. Seven patients (4.9%), four of whom were in the MIX group, had acute arterial occlusive diseases. Conclusions The low frequency of type 1 diabetes in DKA and MIX might be responsible for reduced insulin secretion in Japanese populations. Patients with hyperglycemic crises have increased coagulability, and acute arterial occlusion needs to be considered, particularly in MIX.

Extracorporeal cardiopulmonary resuscitation (ECPR) with extracorporeal membrane oxygenation is a more promising treatment for out-of-hospital cardiac arrest (OHCA) than conventional cardiopulmonary resuscitation (CCPR). However, previous studies that compared ECPR and CCPR included mixed groups of patients with or without target temperature management (TTM). In this study, we compared the neurological outcomes of OHCA between ECPR and CCPR with TTM in all patients. We performed retrospective subanalyses of the Japanese Association for Acute Medicine OHCA registry. Witnessed adult cases of cardiogenic OHCA treated with TTM were eligible for this study. We used univariate and multivariable analyses in all eligible patients to compare the neurological outcomes after ECPR or CCPR. We also conducted propensity score analyses of all patients and according to the interval from witnessed OHCA to reaching the target temperature (IWT) of ≤600, ≤480, ≤360, ≤240, and ≤120 minutes. We analyzed 1146 cases. The propensity score analysis did not show a significant difference in favorable neurological outcomes (defined as a Glasgow-Pittsburgh Cerebral Performance Category of 1-2 at 1 month after collapse) between EPCR and CCPR (odds ratio: OR 4.683 [95% confidence interval: CI 0.859-25.535], p = 0.747). However, ECPR was associated with more favorable neurological outcomes in patients with IWT of ≤600 minutes (OR 7.089 [95% CI 1.091-46.061], p = 0.406), ≤480 minutes (OR 10.492 [95% CI 1.534-71.773], p = 0.0168), ≤360 minutes (OR 17.573 [95% CI 2.486-124.233], p = 0.0042), ≤240 minutes (OR 38.908 [95% CI 5.045-300.089], p = 0.0005), and ≤120 minutes (OR 200.390 [95% CI 23.730-1692.211], p < 0.001). This study revealed significant differences in the neurological outcomes between ECPR and CCPR in patients with TTM whose IWT was ≤600 minutes.

Previous studies have shown inconsistent prognostic accuracy for mortality with both quick sequential organ failure assessment (qSOFA) and the systemic inflammatory response syndrome (SIRS) criteria. We aimed to validate the accuracy of qSOFA and the SIRS criteria for predicting in-hospital mortality in patients with suspected infection in the emergency department. A prospective study was conducted including participants with suspected infection who were hospitalised or died in 34 emergency departments in Japan. Prognostic accuracy of qSOFA and SIRS criteria for in-hospital mortality was assessed by the area under the receiver operating characteristic (AUROC) curve. Of the 1060 participants, 402 (37.9%) and 915 (86.3%) had qSOFA ≥ 2 and SIRS criteria ≥ 2 (given thresholds), respectively, and there were 157 (14.8%) in-hospital deaths. Greater accuracy for in-hospital mortality was shown with qSOFA than with the SIRS criteria (AUROC: 0.64 versus 0.52, difference + 0.13, 95% CI [+ 0.07, + 0.18]). Sensitivity and specificity for predicting in-hospital mortality at the given thresholds were 0.55 and 0.65 based on qSOFA and 0.88 and 0.14 based on SIRS criteria, respectively. To predict in-hospital mortality in patients visiting to the emergency department with suspected infection, qSOFA was demonstrated to be modestly more accurate than the SIRS criteria albeit insufficiently sensitive. Clinical Trial Registration: The study was pre-registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000027258).

Abstract Background Extracorporeal cardiopulmonary resuscitation (ECPR) with extracorporeal membrane oxygenation (ECMO) is a promising therapy for out-of-hospital cardiac arrest (OHCA) compared with conventional cardiopulmonary resuscitation (CCPR). The no and low-flow time (NLT), the interval from collapse to reperfusion to starting ECMO or to the return of spontaneous circulation (ROSC) in CCPR, is associated with the neurological outcome of OHCA. Because the effects of target temperature management (TTM) on the outcomes of ECPR are unclear, we compared the neurological outcomes of OHCA between ECPR and CCPR without TTM. Methods We performed retrospective subanalyses of the Japanese Association for Acute Medicine OHCA registry. Witnessed cases of adult cardiogenic OHCA without TTM were selected. We performed univariate, multivariable and propensity score analyses to compare the neurological outcomes after ECPR or CCPR in all eligible patients and in patients with NLT of > 30 min or > 45 min. Results We analysed 2585 cases. Propensity score analysis showed negative result in all patients (odds ratio 0.328 [95% confidence interval 0.141–0.761], P = 0.010). However, significant associated with better neurological outcome was shown in patients with NLT of > 30 min or > 45 min (odds ratio 2.977 [95% confidence interval 1.056–8.388], P = 0.039, odds ratio 5.099 [95% confidence interval 1.259–20.657], P = 0.023, respectively). Conclusion This study revealed significant differences in the neurological outcomes between ECPR and CCPR without TTM, in patients with NLT of > 30 min.

Aim The quick sequential organ failure assessment (qSOFA) score, shock index (SI), and systemic inflammatory response syndrome (SIRS) criteria are simple indicators for the mortality of patients in the emergency department (ED). These simple indicators using only vital signs might be more useful in prehospital care than in the ED due to their quick calculation. However, these indicators have not been compared in prehospital settings. The aim of the present study is to compare these indicators measured in prehospital care and verify whether the qSOFA score is useful for prehospital triage. Methods We undertook a single-site retrospective study on patients transferred by ambulance to the Kumamoto Medical Center ED (Kumamoto, Japan) between January 2015 and December 2016. We compared areas under the receiver operating characteristic (AUROC) curves of the qSOFA score, SI, and SIRS criteria measured in prehospital care. We also carried out sensitivity and specificity analyses using the Youden index. Results A total of 4,827 patients were included in the present study. The AUROC (95% confidence interval) of the qSOFA score for in-hospital mortality was 0.64 (0.61-0.67), which was significantly higher than those of the SIRS criteria (0.59 [0.56-0.62]) and SI (0.58 [0.54-0.62]). According to the optimal cut-off values (qSOFA >= 2) decided on as the Youden index, the sensitivity of the qSOFA score was 52.3% and its specificity was 69.9%. Conclusions The qSOFA score had the highest AUROC among three indicators. However, it might not be practical in actual prehospital triage due to its low sensitivity.

Aims/Introduction Gestational diabetes mellitus (GDM) is a risk for adverse perinatal outcomes, and patients with a history of GDM have an increased risk of impaired glucose tolerance (IGT). Here, we carried out two non-interventional and retrospective studies of GDM patients in Japan. Materials and Methods In the first study, we enrolled 529 GDM patients and assessed predictors of the need for insulin therapy. In the second study, we enrolled 185 patients from the first study, and assessed predictors of postpartum IGT. Results In the first study, gestational weeks at GDM diagnosis and history of pregnancy were significantly lower, and pregestational body mass index, family history of diabetes mellitus, 1- and 2-h glucose levels in a 75-g oral glucose tolerance test (OGTT), the number of abnormal values in a 75-g OGTT, and glycated hemoglobin were significantly higher in participants receiving insulin therapy. In the second study, 1- and 2-h glucose levels in a 75-g OGTT, the number of abnormal values in a 75-g OGTT, glycated hemoglobin, and ketone bodies in a urine test were significantly higher in participants with OGT. Logistic regression analysis showed that gestational weeks at GDM diagnosis, 1-h glucose levels in a 75-g OGTT and glycated hemoglobin were significant predictors of the need for insulin therapy, and 1-h glucose levels in a 75-g OGTT at diagnosis and ketone bodies in a urine test were significant predictors for postpartum IGT. Conclusions Antepartum 1-h glucose levels in a 75-g OGTT was a predictor of the need for insulin therapy in pregnancy and postpartum IGT.

We conducted a retrospective chart-review study, examining predictors of the repetition of short-term self-harm (<1 month and <6 months) among the patients who were admitted to an emergency department in Japan following self-harm. A total of 405 patients were enrolled and were followed-up for a subsequent one year. The incidence of repeated self-harm within one- and six- months were 6.4% and 13.1%, respectively. Cox's proportional hazards model analyses demonstrated that history of self-harm and comorbid physical illness were associated with repeated self-harm within one month. The patients who lived alone and who were directly discharged from the emergency room after referral to a psychiatrist were at higher risk for repeated self-harm within both one and six months. Living on public assistance and having been discharged from psychiatric wards within the past 12 months were associated with repetition within six months. These risk factors should be incorporated into routine assessment at an emergency room, and elaborate follow-up plan should be provided to the patients with these risk factors upon discharge from the emergency room. Further prospective studies are warranted, addressing more comprehensive factors that are associated with short-term risk for self-harm and suicide.

Objective To ensure good outcomes in the management of subarachnoid haemorrhage (SAH), accurate prediction is crucial for initial assessment of patients presenting with acute headache. We conducted this study to develop a new clinical decision rule using only objectively measurable predictors to exclude SAH, offering higher specificity than the previous Ottawa SAH Rule while maintaining comparable sensitivity. Design Multicentre prospective cohort study. Setting Tertiary-care emergency departments of five general hospitals in Japan from April 2011 to March 2014. Participants Eligible patients comprised 1781 patients aged >15 years with acute headache, excluding trauma or toxic causes and patients who presented in an unconscious state. Main outcome measures Definitive diagnosis of SAH was based on confirmation of SAH on head CT or lumbar puncture findings of non-traumatic red blood cells or xanthochromia. Results A total of 1561 patients were enrolled in this study, of whom 277 showed SAH. Using these enrolled patients, we reached a rule with mainly categorical predictors used in previous reports, called the ‘Ottawa-like rule’, offering 100% sensitivity when using any of age ≥40 years, neck pain or stiffness, altered level of consciousness or onset during exertion. Using the 1317 patients from whom blood samples were obtained, a new rule using any of systolic blood pressure >150 mm Hg, diastolic blood pressure >90 mm Hg, blood sugar >115 mg/dL or serum potassium <3.9 mEq/L offered 100% sensitivity (95% CI 98.6% to 100%) and 14.5% specificity (12.5% to 16.9%), while the Ottawa-like rule showed the same sensitivity with a lower specificity of 8.8% (7.2% to 10.7%). Conclusions While maintaining equal sensitivity, our new rule seemed to offer higher specificity than the previous rules proposed by the Ottawa group. Despite the need for blood sampling, this method can reduce unnecessary head CT in patients with acute headache. Trial registration number UMIN 00004871.

【背景】敗血症性播種性血管内凝固（disseminated intravascular coagulation, DIC）のprotein C（PC）活性と予後の関連を検討した。【方法】2008年10月から2011年1月の単施設での後方視的検討。敗血症性DIC 50例と，その中でDICを離脱した42例を対象とした。重症度，臓器障害，凝固線溶系因子と予後の関係をreceiver operating characteristic曲線を用いて検討した。【結果】敗血症性DIC症例とDIC離脱症例の予後と関連する因子は，DIC診断時のantithrombin（AT）値とPC値で，生存に対するcut-off値はAT≧50.2％，PC≧39.9％だった。陰性反応適中度と感度はATが，陽性反応適中度と特異度はPCが高かった。【結論】敗血症性DICの予後予測には，AT値と同様にPC値も有用である。

咽頭喉頭炎を合併した成人での水痘再感染の症例を経験した。80歳台男性で，関節リウマチに対して副腎皮質ステロイドと抗リウマチ薬を内服中であった。咽頭痛が出現し，数日後より口内炎を発症し，1週間後に躯幹に皮疹が出現し，当院を受診した。高熱と呼吸不全があり，頸部で吸気時狭窄音を聴取した。喉頭内視鏡では著明な咽頭喉頭の浮腫性腫脹を認め，気管挿管による気道確保を要した。頸部，胸腹部には癒合のない丘疹・水疱が多発し，Tzanck試験陽性であった。成人水痘と診断しアシクロビルで治療を行い軽快した。水痘・帯状疱疹ウイルス抗体価は初診時immunoglobulin（Ig）Gのみの上昇であり，2週間後はIgM・IgGの上昇を認め，再感染と考えられた。水痘・帯状疱疹ウイルスは，初感染では水痘を発症し，その後特異的免疫を獲得して，再度水痘は発症しない。免疫抑制状態にある成人は再感染水痘を発症する危険性がある。

【目的】プロカルシトニン(PCT)は全身性感染症,とくに細菌感染症で上昇するといわれているが,一方で外傷などでも受傷後早期に上昇する例が報告されている。そこで,外傷患者における受傷後早期PCTを調査し,外傷部位や外傷の重症度,在院転帰との関連を調査した。【対象と方法】2010年4月1日から2012年2月28日までに国立病院機構の11箇所の救命救急センターを受診し,入院を要した外傷患者を対象とした。重症度,来院時(Day0)および来院後12 ~24時間(Day1)のバイタルサイン,CRPとPCTを記録し,外傷部位や外傷重症度とPCTとの関連について単変量解析を用いて検討し,また在院転帰とPCTの関係について多変量解析を用いて検討した。【結果】218名の患者が登録された。Day0とDay1のCRPとPCTを比較するとほとんどの部位の外傷においてDay1で有意な上昇を認めた。ISS(injury severity score)別にみてみるとDay1のPCTはISSが高値になるほど高くなった。Day1のPCTは頭部,四肢,多発外傷で有意にISS>20群で高くなった。在院転帰に関して調査項目の比較検討を行ったところ,GCSおよびDay1のPCTで有意差を認めた。頭部外傷患者に絞ってロジスティック回帰分析を行ったところ,GCSおよびDay1のPCTが説明変数として選択され,両者を組み合わせたROC曲線下面積は0.98309であった。【結語】外傷患者のDay1のPCTは,頭部,四肢,多発外傷では外傷の重症度が高いほど高値となる。また頭部外傷患者では,GCSとDay1のPCTを組み合わせることで,予後予測に有用である可能性がある。

臭化ジスチグミン（ウブレチド®，鳥居薬品）は排尿困難に使用されるコリンエステラーゼ阻害薬である。重篤な副作用としてコリン作動性クリーゼを起こすことが報告され，その使用量は制限されるようになった。ただ，その後もコリン作動性クリーゼの報告は散見される。我々は，重症肺炎とそれに伴う麻痺性イレウスからショックに至った症例を経験した。当初は敗血症性ショックを疑ったが，臭化ジスチグミンを内服していたことと，コリンエステラーゼ活性の著明な低下を伴っていたことから，コリン作動性クリーゼによるショックが考えられた。臭化ジスチグミンはその大半が便中に排泄されることから，麻痺性イレウスのように消化管蠕動が低下している場合には血中濃度が上昇し，コリン作動性クリーゼを起こす可能性があり注意が必要と思われた。

AIM:Cooling the pharynx and upper oesophagus would be more advantageous for rapid induction of therapeutic hypothermia since the carotid arteries run in their vicinity. The aim of this study was to determine the effects of pharyngeal cooling on brain temperature and the safety and feasibility for patients under resuscitation.METHODS:Witnessed non-traumatic cardiac arrest patients (n=108) were randomized to receive standard care with (n=53) or without pharyngeal cooling (n=55). In the emergency room, pharyngeal cooling was initiated before or shortly after return of spontaneous circulation by perfusing physiological saline (5 °C) into a pharyngeal cuff for 120 min.RESULTS:There was a significant decrease in tympanic temperature at 40 min after arrival (P=0.02) with a maximum difference between the groups at 120 min (32.9 ± 1.2°C, pharyngeal cooling group vs. 34.1 ± 1.3°C, control group; P<0.001). The return of spontaneous circulation (70% vs. 65%, P=0.63) and rearrest (38% vs. 47%, P=0.45) rates were not significantly different based on the initiation of pharyngeal cooling. No post-treatment mechanical or cold-related injury was observed on the pharyngeal epithelium by macroscopic observation. The thrombocytopaenia incidence was lower in the pharyngeal cooling group (P=0.001) during the 3-day period after arrival. The cumulative survival rate at 1 month was not significantly different between the two groups.CONCLUSIONS:Initiation of pharyngeal cooling before or immediately after the return of spontaneous circulation is safe and feasible. Pharyngeal cooling can rapidly decrease tympanic temperature without adverse effects on circulation or the pharyngeal epithelium.