A decreasing plasma concentration of a toxicologically active metabolite 9-carboxymethoxymethylguanine after dialysis - A potential new clinical biomarker for improving encephalopathy in patients treated with acyclovir.

Although acyclovir is a key drug for the treatment of herpes infections, a consciousness disorder known as "acyclovir encephalopathy" is among its side effects. We encountered a patient with encephalopathy and measured the plasma and cerebrospinal fluid concentrations of acyclovir and its toxicologically active metabolite 9-carboxymethoxymethylguanine (CMMG). Before dialysis, cerebrospinal fluid concentrations of acyclovir and CMMG in this patient with a consciousness disorder were approximately 10% and 1%, respectively, of their plasma concentrations. After 3 days of dialysis, plasma CMMG levels decreased to detectable but below quantitative levels (<0.1 µg/mL), resulting in normal consciousness. These results suggest that decreasing plasma CMMG concentration could be one of clinical biomarkers for improving consciousness in patients with encephalopathy associated with acyclovir.

Burnout and Turnover Intention in Critical Care Professionals During the COVID-19 Pandemic in Japan: A Cross-sectional Survey.

Rationale: The prevalence of burnout among critical care professionals during the coronavirus disease (COVID-19) pandemic varies in different countries. Objectives: To investigate the prevalence of burnout and turnover intention in Japanese critical care professionals in March 2021. Methods: This cross-sectional study used a web-based survey of Japanese critical care professionals working in 15 intensive care units in 15 prefectures. Burnout was measured using the Mini Z 2.0 Survey. Intention to leave (turnover intention) was assessed by survey. Resilience was measured using the Brief Resilience Scale (Japanese version). Demographics and personal and workplace characteristics were also collected. Results: Of 1,205 critical care professionals approached, 936 (77.6%) completed the survey. Among these, 24.3%, 20.6%, and 14.2% reported symptoms of burnout, depression, and anxiety, respectively. A total of 157 respondents (16.8%) reported turnover intention. On multivariate analysis, higher resilience scores (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.84-0.95; and OR, 0.94; 95% CI, 0.91-0.96) and perceived support from the hospital (OR, 0.64; 95% CI, 0.44-0.93; and OR, 0.54; 95% CI, 0.40-0.73) were associated with a lower odds of burnout and turnover intention, respectively. Conclusions: Approximately 24% and 17% of the Japanese critical care professionals surveyed had symptoms of burnout and turnover intention from critical care, respectively, during the COVID-19 pandemic. Such professionals require organizational support to cultivate both individual and organizational resilience to reduce burnout and turnover intention.

Prevalence and Risk Factor Analysis of Post-Intensive Care Syndrome in Patients with COVID-19 Requiring Mechanical Ventilation: A Multicenter Prospective Observational Study.

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.

Pharmacokinetics of caffeine self-administered in overdose in a Japanese patient admitted to hospital.

BACKGROUND: Caffeine (0.1 g) is used as a central nervous system stimulant and as a nontoxic phenotyping probe for cytochrome P450 1A2. However, an increasing number of suicide attempts by caffeine overdose have been recently reported. CASE PRESENTATION: A 25-year-old woman (body weight, 43 kg) who intentionally took an overdose of 5.9 g caffeine as a suicide attempt was emergently admitted to Kyoto Medical Center. The plasma concentrations of caffeine and its primary metabolite, N-demethylated paraxanthine, in the current case were 100 and 7.3 µg/mL, 81 and 9.9 µg/mL, 63 and 12 µg/mL, and 21 and 14 µg/mL, at 12, 20, 30, and 56 h after oral overdose, respectively. The observed apparent terminal elimination half-life of caffeine during days 1 and 2 of hospitalization was 27 h, which is several times longer than the reported normal value. This finding implied nonlinearity of caffeine pharmacokinetics over such a wide dose range, which could affect the accuracy of values simulated by a simplified physiologically based pharmacokinetic model founded on a normal dose of 100 mg. Low serum potassium levels (2.9 and 3.5 mM) on days 1 and 2 may have been caused by the caffeine overdose in the current case. CONCLUSIONS: The patient underwent infusion with bicarbonate Ringer's solution and potassium chloride and was discharged on the third day of hospitalization despite taking a potentially lethal dose of caffeine. The virtual plasma exposures of caffeine estimated using the current simplified PBPK model were higher than the measured values. The present results based on drug monitoring data and additional pharmacokinetic predictions could serve as a useful guide in cases of caffeine overdose.

Pharmacokinetics of loxoprofen in a self-administered overdose in a Japanese patient admitted to hospital.

BACKGROUND: Loxoprofen is a propionic acid derivative and is the most widely prescribed non-steroidal anti-inflammatory drug in Japan. Loxoprofen is generally considered to be relatively nontoxic. CASE PRESENTATION: A 33-year-old man (body weight, 55 kg) who intentionally took an overdose of 100 tablets of loxoprofen (6000 mg) as a suicide attempt was emergently admitted to Kyoto Medical Center. On arrival, the patient was suffering disorders of consciousness. His plasma concentrations of loxoprofen and its reduced trans-alcohol metabolite were 52 and 24 µg/mL, 3.7 and 2.3 µg/mL, 0.81 and 0.54 µg/mL, and 0.015 and 0.011 µg/mL, respectively, at 4, 26, 50, and 121 h after the oral overdose. The observed apparent terminal elimination half-life of loxoprofen during days 1 and 2 of hospitalization was in the range 6-12 h, which is several times longer than the reported normal value. This finding implied nonlinearity of loxoprofen pharmacokinetics over the current 100-fold dose range, which could affect the accuracy of values simulated by a simplified physiologically based pharmacokinetic (PBPK) model founded on data from a normal dose of 60 mg. The reasons for the delayed eliminations from plasma of loxoprofen and its trans-alcohol metabolite in this case are uncertain, but slight renal impairment (low eGFR values) developed on the second and third hospital days and could be a causal factor. CONCLUSIONS: Because the patient's level of consciousness had gradually improved, he was discharged on the fourth day of hospitalization. The virtual plasma exposures of loxoprofen and its reduced trans-alcohol metabolite estimated using the current simplified PBPK model were lower than the measured values in the overdose case. The present results based on drug monitoring data and pharmacokinetic predictions could serve as a useful guide in cases of loxoprofen overdose.

Pharmacokinetic modeling of over-the-counter drug diphenhydramine self-administered in overdoses in Japanese patients admitted to hospital.

BACKGROUND: Although the over-the-counter H1 receptor antagonist diphenhydramine is not a common drug of abuse, it was recently recognized as one of the substances causing acute poisoning in patients attempting suicide that led to admissions to our hospital emergency room. CASE PRESENTATION: Two patients [women aged 21 and 27 years (cases 1 and 2)] were emergently admitted after intentionally taking overdoses of 900 and 1200 mg diphenhydramine, respectively. The plasma diphenhydramine concentrations in case 1 were 977 and 425 ng/mL at 2.5 and 11.5 h after single oral overdose, and those in case 2 were 1320 and 475 ng/mL at 3 and 18 h after administration, respectively. We set up a simplified physiologically based pharmacokinetic (PBPK) model that was established using the reported pharmacokinetic data for a microdose of diphenhydramine. The two virtual plasma concentrations and the area under the curve (AUC) values extrapolated using the PBPK model were consistent with the observed overdose data. This finding implied linearity of pharmacokinetics over a wide dosage range for diphenhydramine. CONCLUSIONS: The determined plasma concentrations of diphenhydramine of around 1000 ng/mL at ~ 3 h after orally administered overdoses in cases 1 and 2 may not have been high enough to cause hepatic impairment because levels of aspartate aminotransferase and alanine aminotransferase were normal; however, there was an increase in total bilirubin in case 1. Nonetheless, high virtual liver exposures of diphenhydramine were estimated by the current PBPK model. The present results based on drug monitoring data and pharmacokinetic predictions could serve as a useful guide when setting the duration of treatment in cases of diphenhydramine overdose.

Factors influencing the length of emergency room stay and hospital stay in non-fatal bicycle accidents: A retrospective analysis.

PURPOSE: Lengthy hospitalization places a burden on patients and healthcare resources. However, the factors affecting the length of hospital stay (LHoS) and length of emergency room stay (LERS) in non-fatal bicycle accidents are currently unclear. We investigated these factors to inform efforts to minimize hospitalization. METHODS: We performed a retrospective analysis of data from non-fatal injured bicyclists admitted to the Emergency and Critical Care Center at Kyoto Medical Center between January 2012 and December 2016. We measured LHoS, LERS, mechanism of injury, head injury prevalence, polytrauma, operations performed, injury severity score (ISS), abbreviated injury scale (AIS) score, maximum AIS score, and trauma and injury severity score probability of survival. We conducted multiple regression analysis to determine predictors of LHoS and LERS. RESULTS: Within the study period, 82 victims met the inclusion and exclusion criteria and were included. Mean age was (46.0 ± 24.7) years. Overall mean LHoS was (16.8 ± 25.2) days, mean LERS was (10.6 ± 14.7) days, median ISS was 9 (interquartile range (IQR): 3-16), median maximum AIS was 3 (IQR: 1-4), and median trauma and injury severity score probability of survival was 98.0% (IQR: 95.5%-99.6%). Age, maximum AIS, ISS, and prevalence of surgery were significantly greater in long LHoS and LERS group compared with short LHoS and LERS group (p < 0.05). Performance of surgery independently explained LHoS (p = 0.0003) and ISS independently explained LERS (p = 0.0009). CONCLUSION: Surgery was associated with long hospital stays and ISS was associated with long emergency room stays. To improve the quality life of the bicyclists, preventive measures for reducing injury severity or avoiding injuries needing operation are required.

Pharmacokinetics of duloxetine self-administered in overdose with quetiapine and other antipsychotic drugs in a Japanese patient admitted to hospital.

BACKGROUND: Combinations of antidepressant duloxetine (at doses of 40-60 mg/day) and other antipsychotics are frequently used in clinical treatment; however, several fatal and nonfatal cases of duloxetine overdose have been documented. We experienced a patient who had taken an overdose of duloxetine (780 mg) in combination with other drugs in a suicide attempt. CASE PRESENTATION: The patient was a 37-year-old man (body weight, 64 kg) with a history of gender identity disorder and depression. He intentionally took an overdose of duloxetine in combination with three other antipsychotic drugs (18 mg flunitrazepam, 850 mg quetiapine, and 1100 mg trazodone) and was emergently admitted to Kyoto Medical Center. The patient's plasma concentration of duloxetine during ambulance transport was 57 ng/ml, and the level was still as high as 126 ng/mL at 32 h after administration. Duloxetine disappeared most slowly from plasma, in contrast to quetiapine, which was the fastest to clear among the four medicines determined in this patient. The observed concentrations of duloxetine in this overdose patient were generally within the 95% confidence intervals of the plasma concentration curves predicted using a physiologically based pharmacokinetic (PBPK) model. CONCLUSION: Even if more than 1 h (the generally recommended period) has passed after administration of duloxetine in such overdose cases, gastric lavage and/or administration of activated charcoal may be effective in clinical practice up to 6 h because of the typically slow elimination behavior illustrated by the PBPK model. Pharmacokinetic profiles visualized using PBPK modeling can inform treatment decisions in cases of drug overdose for medicines such as duloxetine in emergency clinical practice.

Pharmacokinetics of anticoagulant edoxaban in overdose in a Japanese patient transported to hospital.

BACKGROUND: The anticoagulant edoxaban is used clinically at doses of 30-60 mg/day; however, we experienced a patient who had taken an overdose of edoxaban of 750 mg. We investigated the pharmacokinetics of edoxaban in this patient by using liquid chromatography-tandem spectrometry to estimate the follow-up period in emergency clinical practice with this medicine. CASE PRESENTATION: The patient was a 57-year-old woman (body weight, 69 kg) who had taken a single oral dose of 750 mg of edoxaban in a suicide attempt. She was emergently admitted to Kyoto Medical Center. The patient's edoxaban plasma concentrations during ambulance transport (8 h after oral administration) were ~ 4900 ng/ml, and the concentration gradually decreased to ~ 10 ng/mL and to detectable but unmeasurable levels of ~ 1.0 ng/mL at 60 h and 100 h, respectively. The linear range of the relationship between the dose and plasma concentration was assumed to have been exceeded during the first 8 h; however, the measured elimination rate of edoxaban was similar to that visualized curves predicted by a simplified physiologically based pharmacokinetic model previously established. CONCLUSION: Simplified physiologically based pharmacokinetic models for creating visualized curves have proven to be useful not only during drug discovery or chemical risk assessment but also in cases of medical poisoning. We used a physiologically based pharmacokinetic model previously established for edoxaban to predict the pharmacokinetics in the current case. It is hoped that the results of this study, which encompass drug monitoring data in the patient and visualized pharmacokinetic prediction, will serve as an index when setting the treatment and follow-up period in cases of drug overdose for medicines such as edoxaban in emergency clinical practice.

Cerebral oxygenation monitoring during resuscitation by emergency medical technicians: a prospective multicenter observational study.

AIM: To assess the feasibility and predictive ability of regional cerebral oxygen saturation monitoring during cardiopulmonary resuscitation by emergency medical technicians. METHODS: This prospective observational study included 33 cardiac arrest patients who received cardiopulmonary resuscitation in a prehospital setting. Patients were connected to a near-infrared spectrometer through two disposable probes immediately after entering the ambulance. The monitor, which showed regional cerebral oxygen saturation readings, was obscured by covering it with a sheet of paper. Regional cerebral oxygen saturation was measured continuously until hospital arrival. Outcome variables included the prehospital return of spontaneous circulation, survival to hospital admission, and survival at 90 days. RESULTS: For patients who survived >90 days after hospital admission (n = 2), the mean regional cerebral oxygen saturation values upon ambulance and hospital arrival were 24% and 60%, respectively; for patients who did not survive (n = 31), the mean regional cerebral oxygen saturation values were 15% and 17%, respectively. Regional cerebral oxygen saturation values increased to a greater extent between ambulance arrival and hospital arrival in patients who survived >90 days (median, 36%; interquartile range, 32-40%) than in those who did not survive (0; 0-6%; P = 0.07). Additionally, regional cerebral oxygen saturation values were not related to the prehospital return of spontaneous circulation or survival to hospital admission. CONCLUSION: Regional cerebral oxygen saturation could be monitored during resuscitation by emergency medical technicians, and it can be used during physiological monitor-guided cardiopulmonary resuscitation.

Transient severe distributive shock due to early dumping syndrome: a case report.

BACKGROUND: Early dumping syndrome characterized by palpitation, dizziness, cold sweat, feebleness, and abdominal symptoms, occurs within 30 minutes after meals in patients who have undergone gastrectomy. This case report describes the case of a patient who presented with severe distributive shock due to early dumping syndrome; he recovered within a few hours after massive fluid infusion and vasopressor administration. CASE PRESENTATION: Our patient was a 68-year-old Japanese man who underwent total gastrectomy for gastric cancer and was diagnosed as having late dumping syndrome. On admission, he developed severe shock and was treated with massive fluid administration. Based on the history of the present illness, past medical history, normal findings of blood chemistry test, transient course, and Sigtad score, which helps diagnose dumping syndrome, early dumping syndrome was considered the cause of severe distributive shock. CONCLUSIONS: Early dumping syndrome can cause severe shock requiring massive fluid infusion and vasopressor administration. It should be considered a cause of severe distributive shock in patients who have undergone gastrectomy.

Tracheal injury detected immediately after median sternotomy by inexperienced surgeons: two case reports.

BACKGROUND: Although median sternotomy is standard during cardiac surgery, the procedure is associated with a risk of injury to mediastinal organs. Here, we discuss two cases of tracheal injury following median sternotomy during cardiac surgery. CASE PRESENTATION: Ventilation failure occurred in a 78-year-old Japanese man and a 71-year-old Japanese man after median sternotomy, and tracheal injury was identified. The sites of injury were directly repaired and covered with mediastinal fat tissue, following which ventilation was successful. The burn-like deposits observed at the site of tracheal injury and on the removed endotracheal tube support the notion that the injuries in our patients were caused by electrocautery prior to median sternotomy. In one case, short sternotracheal distance may have contributed to tracheal injury during post-sternal manipulation. In both cases, the relative inexperience of both surgeons also supports the suspected cause of injury. CONCLUSIONS: Tracheal injury represents a potential complication following median sternotomy, especially when performed by inexperienced surgeons or in cases of short sternotracheal distance. Anesthesiologists should consider this rare yet potentially lethal complication.

Combined short- and long-axis ultrasound-guided central venous catheterization is superior to conventional techniques: A cross-over randomized controlled manikin trial.

OBJECTIVES: Visualizing the needle tip using the short-axis (SA) ultrasound-guided central venous catheterization approach can be challenging. It has been suggested to start the process with the SA approach and then switch to the long-axis (LA); however, to our knowledge, this combination has not been evaluated. We compared the combined short- and long-axis (SLA) approach with the SA approach in a manikin study. METHODS: We performed a prospective randomized controlled cross-over study in an urban emergency department and intensive care unit. Resident physicians in post-graduate years 1-2 performed a simulated ultrasound-guided internal jugular vein puncture using the SA and SLA approaches on manikins. Twenty resident physicians were randomly assigned to two equal groups: (1) one group performed punctures using the SA approach followed by SLA; and (2) the other performed the same procedures in the opposite order. We compared the success rate and procedure duration for the two approaches. Procedural success was defined as insertion of the guide-wire into the vein while visualizing the needle tip at the time of anterior wall puncture, without penetrating the posterior wall. RESULTS: Six resident physicians (30%) performed both approaches successfully, while 12 (60%) performed the SLA approach, but not the SA, successfully. Those who performed the SA approach successfully also succeeded with the SLA approach. Two resident physicians (10%) failed to perform both approaches. The SLA approach had a significantly higher success rate than the SA approach (P < 0.001). The median (interquartile range) procedure duration was 59.5 [46.0-88.5] seconds and 45.0 [37.5-84.0] seconds for the SLA and SA approaches, respectively. The difference of the duration between the two procedures was 15.5 [0-28.5] seconds. There was no significant difference in duration between the two approaches (P = 0.12). CONCLUSIONS: Using the SLA approach significantly improved the success rate of internal jugular vein puncture performed by novice physicians on a manikin model, without increasing procedural duration. Further clinical trials are warranted to confirm the procedure's utility in actual patients. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000026199.

Successful non-operative management of traumatic extrahepatic portal venous injury without intraperitoneal hemorrhage: a case report.

Case: A 52-year-old woman was admitted to our hospital with hypotension after falling from the fifth floor of an apartment building. Contrast-enhanced computed tomography showed liver injury with extravasation of contrast material from the hepatic artery, and extrahepatic portal venous injury with extravasation and pseudoaneurysm. Intra-abdominal hemorrhage was not observed, and bleeding was confined to the retroperitoneal space. Hepatic arteriography showed extravasation, while portal venography showed pseudoaneurysm but no extravasation. After transarterial embolization, the patient's vital signs improved. Non-operative management was selected for the portal venous injury. Outcome: Computed tomography on the 58th hospital day revealed disappearance of the portal venous pseudoaneurysm. The patient was discharged on the 90th hospital day without any complications. Conclusion: This case shows that non-operative management can be selected for portal venous injury when there is no retroperitoneal injury and bleeding is confined to the retroperitoneal space.

Repetitive postoperative extubation failure and cardiac arrest due to laryngomalacia after general anesthesia in an elderly patient: a case report.

The authors report a case involving an elderly patient who experienced repetitive perioperative cardiac arrest caused by laryngomalacia. The patient underwent surgery under general anesthesia; however, 2 h after initial extubation, he experienced cardiopulmonary arrest. Return of spontaneous circulation was achieved by immediate resuscitation. Four hours later, a second extubation was performed without any neurological complications. However, 2 h later, he experienced cardiopulmonary arrest again. Immediately after the third extubation, 12 h after the second cardiopulmonary arrest, fiberoptic laryngoscopy revealed laryngomalacia. His respiratory condition stabilized after emergent tracheostomy. Laryngomalacia should be considered even in adult cases when signs of upper airway obstruction manifest after extubation.

Effect of Dexmedetomidine on Mortality and Ventilator-Free Days in Patients Requiring Mechanical Ventilation With Sepsis: A Randomized Clinical Trial.

Importance: Dexmedetomidine provides sedation for patients undergoing ventilation; however, its effects on mortality and ventilator-free days have not been well studied among patients with sepsis. Objectives: To examine whether a sedation strategy with dexmedetomidine can improve clinical outcomes in patients with sepsis undergoing ventilation. Design, Setting, and Participants: Open-label, multicenter randomized clinical trial conducted at 8 intensive care units in Japan from February 2013 until January 2016 among 201 consecutive adult patients with sepsis requiring mechanical ventilation for at least 24 hours. Interventions: Patients were randomized to receive either sedation with dexmedetomidine (n = 100) or sedation without dexmedetomidine (control group; n = 101). Other agents used in both groups were fentanyl, propofol, and midazolam. Main Outcomes and Measures: The co-primary outcomes were mortality and ventilator-free days (over a 28-day duration). Sequential Organ Failure Assessment score (days 1, 2, 4, 6, 8), sedation control, occurrence of delirium and coma, intensive care unit stay duration, renal function, inflammation, and nutrition state were assessed as secondary outcomes. Results: Of the 203 screened patients, 201 were randomized. The mean age was 69 years (SD, 14 years); 63% were male. Mortality at 28 days was not significantly different in the dexmedetomidine group vs the control group (19 patients [22.8%] vs 28 patients [30.8%]; hazard ratio, 0.69; 95% CI, 0.38-1.22; P = .20). Ventilator-free days over 28 days were not significantly different between groups (dexmedetomidine group: median, 20 [interquartile range, 5-24] days; control group: median, 18 [interquartile range, 0.5-23] days; P = .20). The dexmedetomidine group had a significantly higher rate of well-controlled sedation during mechanical ventilation (range, 17%-58% vs 20%-39%; P = .01); other outcomes were not significantly different between groups. Adverse events occurred in 8 (8%) and 3 (3%) patients in the dexmedetomidine and control groups, respectively. Conclusions and Relevance: Among patients requiring mechanical ventilation, the use of dexmedetomidine compared with no dexmedetomidine did not result in statistically significant improvement in mortality or ventilator-free days. However, the study may have been underpowered for mortality, and additional research may be needed to evaluate this further. Trial Registration: clinicaltrials.gov Identifier: NCT01760967.

Regional cerebral oxygen saturation monitoring for predicting interventional outcomes in patients following out-of-hospital cardiac arrest of presumed cardiac cause: A prospective, observational, multicentre study.

AIM: This study investigated the value of regional cerebral oxygen saturation (rSO2) monitoring upon arrival at the hospital for predicting post-cardiac arrest intervention outcomes. METHODS: We enrolled 1195 patients with out-of-hospital cardiac arrest of presumed cardiac cause from the Japan-Prediction of Neurological Outcomes in Patients Post-cardiac Arrest Registry. The primary endpoint was a good neurologic outcome (cerebral performance categories 1 or 2 [CPC1/2]) 90 days post-event. RESULTS: A total of 68 patients (6%) had good neurologic outcomes. We found a mean rSO2 of 21%±13%. A receiver operating characteristic curve analysis indicated an optimal rSO2 cut-off of ≥40% for good neurologic outcomes (area under the curve 0.92, sensitivity 0.81, specificity 0.96). Good neurologic outcomes were observed in 53% (55/103) and 1% (13/1092) of patients with high (≥40%) and low (<40%) rSO2, respectively. Even without return of spontaneous circulation (ROSC) upon arrival at the hospital, 30% (9/30) of patients with high rSO2 had good neurologic outcomes. Furthermore, 16 patients demonstrating ROSC upon arrival at the hospital and low rSO2 had poor neurologic outcomes. Multivariate analyses indicated that high rSO2 was independently associated with good neurologic outcomes (odds ratio=14.07, P<0.001). Patients with high rSO2 showed favourable neurologic prognoses if they had undergone therapeutic hypothermia or coronary angiography (CPC1/2, 69% [54/78]). However, 24% (25/103) of those with high rSO2 did not undergo these procedures and exhibited unfavourable neurologic prognoses (CPC1/2, 4% [1/25]). CONCLUSION: rSO2 is a good indicator of 90-day neurologic outcomes for post-cardiac arrest intervention patients.

Phosphodiesterase 3 inhibition reduces platelet activation and monocyte tissue factor expression in knee arthroplasty patients.

BACKGROUND: Tissue damage during surgery activates platelets and provokes a prothrombic state. The current study attempted to determine the impact of phosphodiesterase 3 inhibitors on platelet activation, platelet-leukocyte aggregate formation, and monocyte tissue factor expression during and after total knee arthroplasty. METHODS: Thirty-four patients undergoing scheduled total knee arthroplasty were randomly assigned to receive either the phosphodiesterase 3 inhibitor milrinone or the same amount of saline perioperatively. The effects of milrinone on platelet and leukocyte function in vitro were then assessed in healthy volunteers. RESULTS: Perioperative infusion of milrinone significantly attenuated platelet activation; phosphorylation of intraplatelet p38 mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2, and Akt; and platelet-leukocyte aggregation. Furthermore, perioperative tissue factor expression on monocytes and fibrin monomer complex production were reduced by milrinone infusion in patients undergoing total knee arthroplasty. In vitro studies using adenosine diphosphate- and collagen-stimulated blood samples from healthy volunteers confirmed the antiplatelet effects and reduced monocyte tissue factor expression by milrinone. These studies further showed that platelet aggregation and integrin alpha(IIb)beta(3) activation were modified by intraplatelet phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways, and that P-selectin expression on platelets and platelet-leukocyte aggregation were modulated by intraplatelet p38 mitogen-activated protein kinase pathway. CONCLUSION: Continuous milrinone infusion has the potential to reduce platelet activation and monocyte tissue factor expression during the perioperative period in total knee arthroplasty. These events may be mediated in part by the ability of milrinone to reduce activation of intraplatelet mitogen-activated protein kinases and phosphatidylinositol 3-kinase. The clinical impact of phosphodiesterase 3 inhibition on perioperative hemostasis remains to be elucidated.

Acute lung inflammation and ventilator-induced lung injury caused by ATP via the P2Y receptors: an experimental study.

BACKGROUND: Extracellular adenosine 5'-triphosphate (ATP) is an endogenous signaling molecule involved in multiple biological phenomena, including inflammation. The effects of extracellular ATP in the lung have not been fully clarified. This study examined 1) the biological roles of extracellular ATP in the pathogenesis of lung inflammation and 2) the possibility of involvement of extracellular ATP in mechanical ventilation-induced lung injury. METHODS: The effects of intratracheal ATP on lung permeability, edema or lung inflammation were assessed by measurements of the lung wet-to-dry weight ratio and lung permeability index, immunohistochemistry and expression of key cytokines by real-time polymerase chain reaction. The ATP concentration in broncho-alveolar lavage (BAL) fluid from mice mechanically ventilated was measured by luciferin-luciferase assay. The suppressive effects of a P2 receptor antagonist on ventilator-induced lung inflammation were also examined. RESULTS: ATP induced inflammatory reactions in the lung mainly via the ATP-P2Y receptor system. These reactions were alleviated by the co-administration of a specific P2 receptor antagonist. Mechanical ventilation with a large tidal volume caused lung inflammation and increased the ATP concentration in BAL fluid. P2 receptor antagonism partially mitigated the inflammatory effects of large tidal volume ventilation. CONCLUSION: Our observations suggest that the ATP-P2Y receptor system is partially involved in the pathogenesis of ventilator-induced lung injury.