OBJECTIVE: Oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ), which is the ratio of VO2 to VCO2, are critical indicators of human metabolism. To seek a link between the patient's metabolism and pathophysiology of critical illness, we investigated the correlation of these values with mortality in critical care patients. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Age 18 years or older healthy volunteers and patients who underwent mechanical ventilation were enrolled. A high-fidelity automation device, which accuracy is equivalent to the gold standard Douglas Bag technique, was used to measure VO2, VCO2, and RQ at a wide range of fraction of inspired oxygen (FIO2). RESULTS: We included a total of 21 subjects including 8 post-cardiothoracic surgery patients, 7 intensive care patients, 3 patients from the emergency room, and 3 healthy volunteers. This study included 10 critical care patients, whose metabolic measurements were performed in the ER and ICU, and 6 died. VO2, VCO2, and RQ of survivors were 282 +/- 95 mL/min, 202 +/- 81 mL/min, and 0.70 +/- 0.10, and those of non-survivors were 240 +/- 87 mL/min, 140 +/- 66 mL/min, and 0.57 +/- 0.08 (p = 0.34, p = 0.10, and p < 0.01), respectively. The difference of RQ was statistically significant (p < 0.01) and it remained significant when the subjects with FIO2 < 0.5 were excluded (p < 0.05). CONCLUSIONS: Low RQ correlated with high mortality, which may potentially indicate a decompensation of the oxygen metabolism in critically ill patients.

This study aimed to investigate the association between the level of tissue oxygen saturation (StO2) and quadriceps/skeletal muscle dysfunction, measured using the Medical Research Council (MRC) scale and ultrasonography, in critically ill patients. Thirty-four patients hospitalized at the Critical Care Medicine Center of Kindai University Hospital, between January 2022 and March 2023, were enrolled in this study. The StO2 of the quadriceps muscle was measured via near-infrared spectroscopy. Muscle atrophy was measured by the thickness, cross-sectional area (CSA), and echo intensity of the rectus femoris (RF). These values were evaluated every alternate day until 13 days after admission or until discharge, whichever occurred first. Muscle weakness was assessed using the sum score of the MRC scale (MRC-SS), with the patient sitting at bedside. The mean age of the patients was 67.3 ± 15.3 years, and 20 (59%) were men. Seven patients (21%) were admitted for trauma, and 27 (79%) were admitted for medical emergencies or others. The mean score for the MRC-SS was 51.0 ± 7.9 points. RF thickness and CSA significantly decreased after day 7 (p < 0.05). There were no significant changes in StO2 levels during hospitalization. However, there were positive correlations between the nadir StO2 during hospitalization and MRC-SS, and changes in RF thickness and CSA at discharge (r = 0.41, p = 0.03; r = 0.37, p = 0.03; and r = 0.35, p = 0.05, respectively). StO2 in the quadriceps muscle may be useful for predicting muscle atrophy and dysfunction in patients with critical illnesses.

BACKGROUND: Cardiac arrest (CA) is a significant public health concern. There is the high imminent mortality and survival in those who are resuscitated is substantively compromised by the post-CA syndrome (PCAS), characterized by multiorgan ischemia-reperfusion injury (IRI). The inflammatory response in PCAS is complex and involves various immune cell types, including lymphocytes and myeloid cells that have been shown to exacerbate organ IRI, such as myocardial infarction. Purinergic signaling, as regulated by CD39 and CD73, has emerged as centrally important in the context of organ-specific IRI. Hence, comprehensive understanding of such purinergic responses may be likewise imperative for improving outcomes in PCAS. METHODS: We have investigated alterations of immune cell populations after CA by utilizing rodent models of PCAS. Blood and spleen were collected after CA and resuscitation and underwent flow cytometry analysis to evaluate shifts in CD3+CD4+ helper T cells, CD3+CD8a+ cytotoxic T cells, and CD4/CD8a ratios. We then examined the expression of CD39 and CD73 across diverse cell types, including myeloid cells, T lymphocytes, and B lymphocytes. RESULTS: In both rat and mouse models, there were significant increases in the frequency of CD3+CD4+ T lymphocytes in PCAS (rat, P < 0.01; mouse, P < 0.001), with consequently elevated CD4/CD8a ratios in whole blood (both, P < 0.001). Moreover, CD39 and CD73 expression on blood leukocytes were markedly increased (rat, P < 0.05; mouse, P < 0.01 at 24h). Further analysis in the experimental mouse model revealed that CD11b+ myeloid cells, with significant increase in their population (P < 0.01), had high level of CD39 (88.80 ± 2.05 %) and increased expression of CD73 (P < 0.05). CD19+ B lymphocytes showed slight increases of CD39 (P < 0.05 at 2h) and CD73 (P < 0.05 at 2h), while, CD3+ T lymphocytes had decreased levels of them. These findings suggested a distinct patterns of expression of CD39 and CD73 in these specific immune cell populations after CA. CONCLUSIONS: These data have provided comprehensive insights into the immune response after CA, highlighting high-level expressions of CD39 and CD73 in myeloid cells.

OBJECTIVE: Using a system, which accuracy is equivalent to the gold standard Douglas Bag (DB) technique for measuring oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ), we aimed to continuously measure these metabolic indicators and compare the values between post-cardiothoracic surgery and critical care patients. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Age 18 years or older patients who underwent mechanical ventilation were enrolled. RESULTS: We included 4 post-surgery and 6 critical care patients. Of those, 3 critical care patients died. The longest measurement reached to 12 h and 15 min and 50 cycles of repeat measurements were performed. VO2 of the post-surgery patients were 234 ± 14, 262 ± 27, 212 ± 16, and 192 ± 20 mL/min, and those of critical care patients were 122 ± 20, 189 ± 9, 191 ± 7, 191 ± 24, 212 ± 12, and 135 ± 21 mL/min, respectively. The value of VO2 was more variable in the post-surgery patients and the range of each patient was 44, 126, 71, and 67, respectively. SOFA scores were higher in non-survivors and there were negative correlations of RQ with SOFA. CONCLUSIONS: We developed an accurate system that enables continuous and repeat measurements of VO2, VCO2, and RQ. Critical care patients may have less activity in metabolism represented by less variable values of VO2 and VCO2 over time as compared to those of post-cardiothoracic surgery patients. Additionally, an alteration of these values may mean a systemic distinction of the metabolism of critically ill patients.

In this case study, we describe a 25-year-old male who was admitted due to a severe traumatic brain injury, requiring invasive intracranial pressure monitoring. At 48 hours posttrauma, he developed intracranial hypertension refractory to medical treatment without tomographic changes in the brain. Subsequently, intra-abdominal hypertension and tomographic signs of abdominal surgical pathology were observed. An exploratory laparotomy was performed with an intraoperative diagnosis of acute mesenteric ischemia. After surgical intervention for the abdominal pathology, intracranial pressure was restored to physiological values with a favorable recovery of the patient. In this report, the relationship between intracranial pressure and intra-abdominal pressure is discussed, highlighting the delicate association between the brain, abdomen, and thorax. Measures should be taken to avoid increases in intra-abdominal pressure in neurocritical patients. When treating intracranial hypertension refractory to conventional measures, abdominal causes and multiple compartment syndrome must be considered. The cranial compartment has physiological interdependence with other body compartments, where one can be modified by variations from another, giving rise to the concept of multiple compartment syndrome. Understanding this relationship is fundamental for a comprehensive approach of the neurocritical patient. To the best of our knowledge, this is the first report of a comatose patient post-traumatic brain injury, who developed medically unresponsive intracranial hypertension secondary to acute mesenteric ischemia, in which surgical resolution of intra-abdominal pathology resulted in intracranial pressure normalization and restitutio ad integrum of neurological status.

Purine nucleotide adenosine triphosphate (ATP) is a source of intracellular energy maintained by mitochondrial oxidative phosphorylation. However, when released from ischemic cells into the extracellular space, they act as death-signaling molecules (eATP). Despite there being potential benefit in using pyruvate to enhance mitochondria by inducing a highly oxidative metabolic state, its association with eATP levels is still poorly understood. Therefore, while we hypothesized that pyruvate could beneficially increase intracellular ATP with the enhancement of mitochondrial function after cardiac arrest (CA), our main focus was whether a proportion of the raised intracellular ATP would detrimentally leak out into the extracellular space. As indicated by the increased levels in systemic oxygen consumption, intravenous administrations of bolus (500 mg/kg) and continuous infusion (1000 mg/kg/h) of pyruvate successfully increased oxygen metabolism in post 10-min CA rats. Plasma ATP levels increased significantly from 67 ± 11 nM before CA to 227 ± 103 nM 2 h after the resuscitation; however, pyruvate administration did not affect post-CA ATP levels. Notably, pyruvate improved post-CA cardiac contraction and acidemia (low pH). We also found that pyruvate increased systemic CO2 production post-CA. These data support that pyruvate has therapeutic potential for improving CA outcomes by enhancing oxygen and energy metabolism in the brain and heart and attenuating intracellular hydrogen ion disorders, but does not exacerbate the death-signaling of eATP in the blood.

Predicting out-of-hospital cardiac arrest (OHCA) events might improve outcomes of OHCA patients. We hypothesized that machine learning algorithms using meteorological information would predict OHCA incidences. We used the Japanese population-based repository database of OHCA and weather information. The Tokyo data (2005-2012) was used as the training cohort and datasets of the top six populated prefectures (2013-2015) as the test. Eight various algorithms were evaluated to predict the high-incidence OHCA days, defined as the daily events exceeding 75% tile of our dataset, using meteorological and chronological values: temperature, humidity, air pressure, months, days, national holidays, the day before the holidays, the day after the holidays, and New Year's holidays. Additionally, we evaluated the contribution of each feature by Shapley Additive exPlanations (SHAP) values. The training cohort included 96,597 OHCA patients. The eXtreme Gradient Boosting (XGBoost) had the highest area under the receiver operating curve (AUROC) of 0.906 (95% confidence interval; 0.868-0.944). In the test cohorts, the XGBoost algorithms also had high AUROC (0.862-0.923). The SHAP values indicated that the "mean temperature on the previous day" impacted the most on the model. Algorithms using machine learning with meteorological and chronological information could predict OHCA events accurately.

Background: Cardiac arrest (CA) can lead to neuronal degeneration and death through various pathways, including oxidative, inflammatory, and metabolic stress. However, current neuroprotective drug therapies will typically target only one of these pathways, and most single drug attempts to correct the multiple dysregulated metabolic pathways elicited following cardiac arrest have failed to demonstrate clear benefit. Many scientists have opined on the need for novel, multidimensional approaches to the multiple metabolic disturbances after cardiac arrest. In the current study, we have developed a therapeutic cocktail that includes ten drugs capable of targeting multiple pathways of ischemia–reperfusion injury after CA. We then evaluated its effectiveness in improving neurologically favorable survival through a randomized, blind, and placebo-controlled study in rats subjected to 12 min of asphyxial CA, a severe injury model. Results: 14 rats were given the cocktail and 14 received the vehicle after resuscitation. At 72 h post-resuscitation, the survival rate was 78.6% among cocktail-treated rats, which was significantly higher than the 28.6% survival rate among vehicle-treated rats (log-rank test; p = 0.006). Moreover, in cocktail-treated rats, neurological deficit scores were also improved. These survival and neurological function data suggest that our multi-drug cocktail may be a potential post-CA therapy that deserves clinical translation. Conclusions: Our findings demonstrate that, with its ability to target multiple damaging pathways, a multi-drug therapeutic cocktail offers promise both as a conceptual advance and as a specific multi-drug formulation capable of combatting neuronal degeneration and death following cardiac arrest. Clinical implementation of this therapy may improve neurologically favorable survival rates and neurological deficits in patients suffering from cardiac arrest.

Abstract Cardiac arrest (CA) and concomitant post‐CA syndrome lead to a lethal condition characterized by systemic ischemia–reperfusion injury. Oxygen (O₂) supply during cardiopulmonary resuscitation (CPR) is the key to success in resuscitation, but sustained hyperoxia can produce toxic effects post CA. However, only few studies have investigated the optimal duration and dosage of O₂ administration. Herein, we aimed to determine whether high concentrations of O₂ at resuscitation are beneficial or harmful. After rats were resuscitated from the 10‐min asphyxia, mechanical ventilation was restarted at an FIO₂ of 1.0 or 0.3. From 10 min after initiating CPR, FIO₂ of both groups were maintained at 0.3. Bio‐physiological parameters including O₂ consumption (VO₂) and mRNA gene expression in multiple organs were evaluated. The FIO₂ 0.3 group decreased VO₂, delayed the time required to achieve peak MAP, lowered ejection fraction (75.1 ± 3.3% and 59.0 ± 5.7% with FIO₂ 1.0 and 0.3, respectively; p < .05), and increased blood lactate levels (4.9 ± 0.2 mmol/L and 5.6 ± 0.2 mmol/L, respectively; p < .05) at 10 min after CPR. FIO₂ 0.3 group had significant increases in hypoxia‐inducible factor, inflammatory, and apoptosis‐related mRNA gene expression in the brain. Likewise, significant upregulations of hypoxia‐inducible factor and apoptosis‐related gene expression were observed in the FIO₂ 0.3 group in the heart and lungs. Insufficient O₂ supplementation in the first 10 min of resuscitation could prolong ischemia, and may result in unfavorable biological responses 2 h after CA. Faster recovery from the impairment of O₂ metabolism might contribute to the improvement of hemodynamics during the early post‐resuscitation phase; therefore, it may be reasonable to provide the maximum feasible O₂ concentrations during CPR.

Oxidative stress is believed to be a major cause of injury after cardiac arrest (CA). While the effects of ROS generated within tissues have been extensively investigated, the potential of plasma-generated ROS in contributing to CA pathology has not been examined. We utilized Amplex Red (AR) to measure the real time-generation of ROS in isolated plasma from human CA patients. We first used post-CA rat plasma to identify interfering factors for AR oxidation, and then applied this knowledge to analyze human plasma samples, accounting for the identified confounders. We found significantly increased AR oxidation rates lasting for 4 h in post-CA rat plasma compared to baseline. AR oxidation was unchanged with removal of horseradish peroxidase or addition of catalase. However, adding carboxylesterase inhibitors significantly decreased AR oxidation in rat plasma, which implicated increased carboxylesterase activity, not ROS leading to increased AR oxidation. AR oxidation rates were also significantly increased in human CA patient plasma compared to control and this increase persisted even with carboxylesterase inhibition, suggesting continuously increased ROS-generation within plasma post-CA in humans. The increased ROS generation may be one major source of injury post-CA that may be mitigated with antioxidative therapeutic strategies that can manage the ROS systemically generated in plasma over time.KEY POLICY HIGHLIGHTSWe examined the potential of plasma as a source of ROS generation post-cardiac arrestRat cardiac arrest was used to guide the application of Amplex Red in human plasmaROS generation in plasma is significantly increased after cardiac arrest in humansScavenging excessive ROS in post-resuscitation plasma may improve outcomes of patients.

Abstract Background Mitochondrial transplantation (MTx) is an emerging but poorly understood technology with the potential to mitigate severe ischemia–reperfusion injuries after cardiac arrest (CA). To address critical gaps in the current knowledge, we test the hypothesis that MTx can improve outcomes after CA resuscitation. Methods This study consists of both in vitro and in vivo studies. We initially examined the migration of exogenous mitochondria into primary neural cell culture in vitro. Exogenous mitochondria extracted from the brain and muscle tissues of donor rats and endogenous mitochondria in the neural cells were separately labeled before co-culture. After a period of 24 h following co-culture, mitochondrial transfer was observed using microscopy. In vitro adenosine triphosphate (ATP) contents were assessed between freshly isolated and frozen-thawed mitochondria to compare their effects on survival. Our main study was an in vivo rat model of CA in which rats were subjected to 10 min of asphyxial CA followed by resuscitation. At the time of achieving successful resuscitation, rats were randomly assigned into one of three groups of intravenous injections: vehicle, frozen-thawed, or fresh viable mitochondria. During 72 h post-CA, the therapeutic efficacy of MTx was assessed by comparison of survival rates. The persistence of labeled donor mitochondria within critical organs of recipient animals 24 h post-CA was visualized via microscopy. Results The donated mitochondria were successfully taken up into cultured neural cells. Transferred exogenous mitochondria co-localized with endogenous mitochondria inside neural cells. ATP content in fresh mitochondria was approximately four times higher than in frozen-thawed mitochondria. In the in vivo survival study, freshly isolated functional mitochondria, but not frozen-thawed mitochondria, significantly increased 72-h survival from 55 to 91% (P = 0.048 vs. vehicle). The beneficial effects on survival were associated with improvements in rapid recovery of arterial lactate and glucose levels, cerebral microcirculation, lung edema, and neurological function. Labeled mitochondria were observed inside the vital organs of the surviving rats 24 h post-CA. Conclusions MTx performed immediately after resuscitation improved survival and neurological recovery in post-CA rats. These results provide a foundation for future studies to promote the development of MTx as a novel therapeutic strategy to save lives currently lost after CA.

Abstract Cardiac arrest (CA) patients suffer from systemic ischemia–reperfusion (IR) injury leading to multiple organ failure; however, few studies have focused on tissue-specific pathophysiological responses to IR-induced oxidative stress. Herein, we investigated biological and physiological parameters of the brain and heart, and we particularly focused on the lung dysfunction that has not been well studied to date. We aimed to understand tissue-specific susceptibility to oxidative stress and tested how oxygen concentrations in the post-resuscitation setting would affect outcomes. Rats were resuscitated from 10 min of asphyxia CA. Mechanical ventilation was initiated at the beginning of cardiopulmonary resuscitation. We examined animals with or without CA, and those were further divided into the animals exposed to 100% oxygen (CA_Hypero) or those with 30% oxygen (CA_Normo) for 2 h after resuscitation. Biological and physiological parameters of the brain, heart, and lungs were assessed. The brain and lung functions were decreased after CA and resuscitation indicated by worse modified neurological score as compared to baseline (222 ± 33 vs. 500 ± 0, P < 0.05), and decreased PaO2 (20 min after resuscitation: 113 ± 9 vs. baseline: 128 ± 9 mmHg, P < 0.05) and increased airway pressure (2 h: 10.3 ± 0.3 vs. baseline: 8.1 ± 0.2 mmHg, P < 0.001), whereas the heart function measured by echocardiography did not show significant differences compared before and after CA (ejection fraction, 24 h: 77.9 ± 3.3% vs. baseline: 82.2 ± 1.9%, P = 0.2886; fractional shortening, 24 h: 42.9 ± 3.1% vs. baseline: 45.7 ± 1.9%, P = 0.4658). Likewise, increases of superoxide production in the brain and lungs were remarkable, while those in the heart were moderate. mRNA gene expression analysis revealed that CA_Hypero group had increases in Il1b as compared to CA_Normo group significantly in the brain (P < 0.01) and lungs (P < 0.001) but not the heart (P = 0.4848). Similarly, hyperoxia-induced increases in other inflammatory and apoptotic mRNA gene expression were observed in the brain, whereas no differences were found in the heart. Upon systemic IR injury initiated by asphyxia CA, hyperoxia-induced injury exacerbated inflammation/apoptosis signals in the brain and lungs but might not affect the heart. Hyperoxia following asphyxia CA is more damaging to the brain and lungs but not the heart.

Sudden cardiac arrest (CA) is the third leading cause of death. Immediate reoxygenation with high concentrations of supplemental oxygen (O2) during cardiopulmonary resuscitation (CPR) is recommended according to the current guidelines for adult CA. However, a point in controversy exists because of the known harm of prolonged exposure to 100% O2. Therefore, there have been much debate on an optimal use of supplemental O2, yet little is known about the duration and dosage of O2 administration. To test whether supplying a high concentration of O2 during CPR and post resuscitation is beneficial or harmful, rats subjected to 10-minute asphyxia CA were administered either 100% O2 (n = 8) or 30% O2 (n = 8) for 2 hours after CPR. Two hours after initiating CPR, the brain, lung, and heart tissues were collected to compare mRNA gene expression levels of inflammatory cytokines, apoptotic and oxidative stress-related markers. The 100% O2 group had significantly shorter time to return of spontaneous circulation (ROSC) than the 30% O2 group (62.9 ± 2.2 and 77.5 ± 5.9 seconds, respectively, P < 0.05). Arterial blood gas analysis revealed that the 100% O2 group had significantly higher PaCO2 (49.4 ± 4.9 mmHg and 43.0 ± 3.0 mmHg, P < 0.01), TCO2 (29.8 ± 2.7 and 26.6 ± 1.1 mmol/L, P < 0.05), HCO3- (28.1 ± 2.4 and 25.4 ± 1.2 mmol/L, P < 0.05), and BE (2.6 ± 2.3 and 0.1 ± 1.4 mmol/L, P < 0.05) at 2 hours after initiating CPR, but no changes in pH (7.37 ± 0.03 and 7.38 ± 0.03, ns). Inflammation- (Il6, Tnf) and apoptosis- (Casp3) related mRNA gene expression levels were significantly low in the 100% O2 group in the brain, however, oxidative stress moderator Hmox1 increased in the 100% O2 group. Likewise, mRNA gene expression of Icam1, Casp9, Bcl2, and Bax were low in the 100% O2 group in the lung. Contrarily, mRNA gene expression of Il1b and Icam1 were low in the 30% O2 group in the heart. Supplying 30% O2 during and after CPR significantly delayed the time to ROSC and increased inflammation-/apoptosis- related gene expression in the brain and lung, indicating that insufficient O2 was associated with unfavorable biological responses post CA, while prolonged exposure to high-concentration O2 should be still cautious in general.

PURPOSE: To develop a system that is equivalent to the gold standard Douglas Bag (DB) technique for measuring oxygen consumption (V̇o2), carbon dioxide generation (V̇co2), and respiratory quotient (RQ) and to validate its use in clinical settings. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Healthy volunteers and patients 18 years or older who received mechanical ventilation were enrolled. FINDINGS: Data from 3 healthy volunteers and 7 patients were analyzed in this study. The interrater reliability between the automation device and DB methods were 0.999, 0.993, and 0.993 for V̇o2, V̇co2, and RQ, respectively. In healthy volunteers, mean (SD) V̇o2, V̇co2, and RQ measured by DB were 411 (100) mL/min, 288 (79) mL/min, and 0.70 (0.03) at high fraction of inspired oxygen (Fio2) and 323 (46) mL/min, 280 (45) mL/min, and 0.85 (0.05) at normal Fio2, respectively. V̇o2 was significantly higher (P < 0.05) and RQ was lower (P < 0.01) in the high Fio2 group as compared to those in the normal Fio2 group. Values measured by the automation system were 227 (31) mL/min, 141 (18) mL/min, and 0.62 (0.04) at high Fio2 and 209 (25) mL/min, 147 (18) mL/min, and 0.70 (0.06) at normal Fio2, respectively. RQ was significantly lower (P < 0.05) in the high Fio2 group as compared to the normal Fio2 group. We also successfully performed continuous and repeat measurements by using the device. The longest measurement reached 12 hours 15 minutes, including 50 cycles of repeat measurements that are equivalent to the DB technique as described above. IMPLICATIONS: We developed an automation system that enables repeat measurements of V̇o2, V̇co2, and RQ, and the accuracy was equivalent to the DB technique. High Fio2 may decrease RQ because of an increase in V̇o2.

Abstract Upper-extremity deep venous thrombosis (UEDVT) after whole blood donation is rarely reported. Blood donation has a low rate of complications and is typically safe. A small percentage of blood donors experience donation-related events such as UEDVT, which are extremely rare. We are reporting a rare case of a UEDVT following blood donation. This is an extremely rare event; only five cases were reported to our knowledge. A 22-year-old Caucasian woman with a past medical history of provoked pulmonary embolism completed 6 months of apixaban and negative thrombophilia workup presented to the hospital with complaints of progressive pain and swelling in her right arm. The patient reports donating blood using her right arm in January 2021. Phlebotomy duration for blood donation was approximately 10minutes. She reported pain and swelling several days after blood donation. Subsequently, a duplex ultrasound showed a thrombus in the right brachial vein. The patient was started on apixaban for 6 months. Although most whole blood donors do not experience complications, DVT is a rare complication from whole blood donation with severe consequences. It should be considered in a donor with worsening pain and swelling.

Rationale: During the first wave of the coronavirus disease (COVID-19) pandemic in New York City, the number of mechanically ventilated COVID-19 patients rapidly surpassed the capacity of traditional intensive care units (ICUs), resulting in health systems utilizing other areas as expanded ICUs to provide critical care. Objectives: To evaluate the mortality of patients admitted to expanded ICUs compared with those admitted to traditional ICUs. Methods: Multicenter, retrospective, cohort study of mechanically ventilated patients with COVID-19 admitted to the ICUs at 11 Northwell Health hospitals in the greater New York City area between March 1, 2020 and April 30, 2020. Primary outcome was in-hospital mortality up to 28 days after intubation of COVID-19 patients. Results: Among 1,966 mechanically ventilated patients with COVID-19, 1,198 (61%) died within 28 days after intubation, 46 (2%) were transferred to other hospitals outside of the Northwell Health system, 722 (37%) survived in the hospital until 28 days or were discharged after recovery. The risk of mortality of mechanically ventilated patients admitted to expanded ICUs was not different from those admitted to traditional ICUs (hazard ratio [HR], 1.07; 95% confidence interval [CI], 0.95-1.20; P = 0.28), while hospital occupancy for critically ill patients itself was associated with increased risk of mortality (HR, 1.28; 95% CI, 1.12-1.45; P < 0.001). Conclusions: Although increased hospital occupancy for critically ill patients itself was associated with increased mortality, the risk of 28-day in-hospital mortality of mechanically ventilated patients with COVID-19 who were admitted to expanded ICUs was not different from those admitted to traditional ICUs.

BACKGROUND: Vagus nerve stimulation (VNS) has shown therapeutic potential in a variety of different diseases with many ongoing clinical trials. The role of VNS in reducing ischemic injury in the brain requires further evaluation. Cardiac arrest (CA) causes global ischemia and leads to the injury of vital organs, especially the brain. In this study, we investigated the protective effects of customized threshold-adjusted VNS (tVNS) in a rat model of CA and resuscitation. METHODS: Sprague-Dawley rats underwent 12 min asphyxia-CA followed by resuscitation. Rats were assigned to either post-resuscitation tVNS for 2 h or no-tVNS (control). tVNS was applied by electrode placement in the left cervical vagus nerve. To optimize a threshold, we used animal's heart rate and determined a 15-20% drop from baseline levels as the effective and physiological threshold for each animal. The primary endpoint was 72 h survival; secondary endpoints included neurological functional recovery, reduction in brain cellular injury (histopathology), cardiac and renal injury parameters (troponin I and creatinine levels, respectively). RESULTS: In comparison to the control group, tVNS significantly improved 72 h survival and brain functional recovery after 12 minutes of CA. The tVNS group demonstrated significantly reduced numbers of damaged neurons in the CA1 hippocampal region of the brain as compared to the control group. Similarly, the tVNS group showed decreased trend in plasma troponin I and creatinine levels as compared to the control group. CONCLUSIONS: Our findings suggest that using tVNS for 2 h after 12 minutes of CA attenuates ischemia neuronal cell death, heart and kidney damage, and improves 72 h survival with improved neurological recovery.

Stenosis proximal to transplant renal artery anastomoses are complications leading to allograft dysfunction. This study was aimed to evaluate a novel surgical approach to renal allograft revascularization, taking into consideration the length of time elapsed since transplantation. We describe an arterial bypass using a polytetrafluoroethylene (PTFE) graft from the common iliac artery (proximal to the renal artery implantation) to the external iliac artery (distal to the renal artery implantation) that allows the adequate revascularization of both the transplant kidney, as well as the lower extremity. This technique provides several advantages when compared with previously described procedures to revascularize a transplanted kidney with an iliac artery stenosis proximal to the allograft implantation site. Benefits of this technique include (1) no need to repair the stenosis, (2) no need to take down and redo the arterial anastomosis, (3) no need to perform a dissection around the renal hilum of the transplanted kidney, (4) no requirement to address the anastomosis transfer, and (5) no need to perfuse the kidney with preservation fluid at the time of repair and/or (6) avoidance of potential injury to the renal parenchyma and/or hilum during dissections. Adequate perfusion of the organ, as well as of the lower extremity was verified by serial Doppler duplex ultrasound evaluations. Hence, we describe a novel revascularization technique in instances of kidney transplant and lower extremity ischemia.

Abstract This case study describes a 45-year-old Caucasian male with a past medical history of obesity, hypertension, and non-insulin-dependent diabetes mellitus, who in the setting of coronavirus disease 2019 (COVID-19) pneumonia, developed portal vein thrombosis (PVT) presenting as an acute abdomen after hospital discharge from a cholecystitis episode. PVT is a very infrequent thromboembolic condition, classically occurring in patients with systemic conditions such as cirrhosis, malignancy, pancreatitis, diverticulitis, autoimmunity, and thrombophilia. PVT can cause serious complications, such as intestinal infarction, or even death, if not promptly treated. Due to the limited number of reports in the literature describing PVT in the COVID-19 setting, its prevalence, natural history, mechanism, and precise clinical features remain unknown. Therefore, clinical suspicion should be high for PVT, in any COVID-19 patient who presents with abdominal pain or associated signs and symptoms. To the best of our knowledge, this is the first report of COVID-19-associated PVT causing extensive thrombosis in the portal vein and its right branch, occurring in the setting of early-stage cirrhosis after a preceding episode of cholecystitis.

Cerebral blood oxygenation (CBO), measured using near-infrared spectroscopy (NIRS), can play an important role in post-cardiac arrest (CA) care as this emerging technology allows for noninvasive real-time monitoring of the dynamic changes of tissue oxygenation. We recently reported that oxyhaemoglobin (oxy-Hb), measured using NIRS, may be used to evaluate the quality of chest compressions by monitoring the brain tissue oxygenation, which is a critical component for successful resuscitation. Mitochondria are the key to understanding the pathophysiology of post-CA oxygen metabolism. In this study, we focused on mitochondrial dysfunction, aiming to explore its association with CBO parameters such as oxy-Hb and deoxyhaemoglobin (deoxy-Hb) or tissue oxygenation index (TOI). Male Sprague-Dawley rats were used in the study. We applied NIRS between the nasion and the upper cervical spine. Following 10 min of CA, the rats underwent cardiopulmonary resuscitation (CPR) with a bolus injection of 20 μg/kg epinephrine. At 10 and 20 min after CPR, brain, and kidney tissues were collected. We isolated mitochondria from these tissues and evaluated the association between CBO and mitochondrial oxygen consumption ratios. There were no significant differences in the mitochondrial yields (10 vs. 20 min after resuscitation: brain, 1.33 ± 0.68 vs. 1.30 ± 0.75 mg/g; kidney, 19.5 ± 3.2 vs. 16.9 ± 5.3 mg/g, respectively). State 3 mitochondrial oxygen consumption rates, known as ADP-stimulated respiration, demonstrated a significant difference at 10 vs. 20 min after CPR (brain, 170 ± 26 vs. 115 ± 17 nmol/min/mg protein; kidney, 170 ± 20 vs. 130 ± 16 nmol/min/mg protein, respectively), whereas there was no significant difference in ADP non-dependent state 4 oxygen consumption rates (brain, 34.0 ± 6.7 vs. 31.8 ± 10 nmol/min/mg protein; kidney, 29.8 ± 4.8 vs. 21.0 ± 2.6 nmol/min/mg protein, respectively). Consequently, the respiratory control ratio (RCR = state 3/state 4) showed a significant difference over time, but this was only noted in the brain (brain, 5.0 ± 0.29 vs. 3.8 ± 0.64; kidney, 5.8 ± 0.53 vs. 6.2 ± 0.25 nmol/min/mg protein, respectively). The oxy-Hb levels had a dynamic change after resuscitation, and they had a significant association with the RCR of the brain mitochondria (r = 0.8311, p = 0.0102), whereas deoxy-Hb and TOI did not (r = -0.1252, p = 0.7677; r = 0.4186, p = 0.302, respectively). The RCRs of the kidney mitochondria did not have a significant association with CBO (oxy-Hb, r = -0.1087, p = 0.7977; deoxy-Hb, r = 0.1565, p = 0.7113; TOI, r = -0.1687, p = 0.6896, respectively). The brain mitochondrial respiratory dysfunction occurred over time, and it was seen at the time points between 10 and 20 min after CPR. The oxy-Hb level was associated with brain mitochondrial dysfunction during the early post-resuscitation period.

BACKGROUND: Acute mesenteric ischemia (AMI) is challenging to diagnose in the early phase. We tested the hypothesis that blood levels of cell-free DNA would increase early after AMI. In addition, proteome analysis was conducted as an exploratory analysis to identify other potential diagnostic biomarkers. METHODS: Mesenteric ischemia, abdominal sepsis, and sham model were compared in Sprague-Dawley rats. The abdominal sepsis model was induced by cecum puncture and mesenteric ischemia model by ligation of the superior mesenteric artery. Blood levels of cell-free DNA were measured 2 h and 6 h after wound closure. Shotgun proteome analysis was performed using plasma samples obtained at the 2 h timepoint; quantitative analysis was conducted for proteins detected exclusively in the AMI models. RESULTS: Blood cell-free DNA levels at 2 h after wound closure were significantly higher in the AMI model than in the sham and the abdominal sepsis models (P < 0.05). Cell-free DNA was positively correlated with the pathologic ischemia severity score (correlation coefficient 0.793-0.834, P < 0.001). Derivative proteome analysis in blood at 2-h time point revealed higher intensity of paraoxonase-1 in the AMI models than in the abdominal sepsis models; the significantly high blood paraoxonase-1 levels in the AMI models were confirmed in a separate quantitative analysis (P = 0.015). CONCLUSIONS: Cell-free DNA was demonstrated to be a promising biomarker for the early diagnosis of mesenteric ischemia in a rat model of AMI. Paraoxonase-1 may also play a role in the differential diagnosis of mesenteric ischemia from abdominal sepsis. The current results warrant further investigation in human studies.

In this case report we describe a novel and successful revascularization approach in instances of allograft and distal limb ischemia after kidney transplantation. Stenosis proximal to transplant renal artery anastomoses is a complication leading to allograft dysfunction and/or loss. We present a femorofemoral bypass graft with ringed polytetrafluoroethylene (PTFE). In this occasion, revascularization was achieved by a backflow mechanism. The approach described achieved its goal of revascularizing the allograft as well as the distal extremity, with both short- and long-term successful outcomes. Benefits of this approach when compared with re-implantation or procedures directly involving the transplant renal artery include minimization of ischemic time, no need to repair the stenosis, anastomoses with vessels of greater diameter, no need to perfuse the kidney, no need to take down the renal artery anastomosis, no need to dissect the transplanted kidney, and no further lower extremity ischemia. This approach does not require any proximal temporary inflow occlusion (as seen with stent placement) or clamping of the arterial inflow to the kidney. This procedure was completed without having to infuse any preservation fluid into the kidney.

BACKGROUND: Despite the benefits of extracorporeal cardiopulmonary resuscitation (ECPR) in cohorts of selected patients with cardiac arrest (CA), extracorporeal membrane oxygenation (ECMO) includes an artificial oxygenation membrane and circuits that contact the circulating blood and induce excessive oxidative stress and inflammatory responses, resulting in coagulopathy and endothelial cell damage. There is currently no pharmacological treatment that has been proven to improve outcomes after CA/ECPR. We aimed to test the hypothesis that administration of hydrogen gas (H2) combined with ECPR could improve outcomes after CA/ECPR in rats. METHODS: Rats were subjected to 20 min of asphyxial CA and were resuscitated by ECPR. Mechanical ventilation (MV) was initiated at the beginning of ECPR. Animals were randomly assigned to the placebo or H2 gas treatment groups. The supplement gas was administered with O2 through the ECMO membrane and MV. Survival time, electroencephalography (EEG), brain functional status, and brain tissue oxygenation were measured. Changes in the plasma levels of syndecan-1 (a marker of endothelial damage), multiple cytokines, chemokines, and metabolites were also evaluated. RESULTS: The survival rate at 4 h was 77.8% (7 out of 9) in the H2 group and 22.2% (2 out of 9) in the placebo group. The Kaplan-Meier analysis showed that H2 significantly improved the 4 h-survival endpoint (log-rank P = 0.025 vs. placebo). All animals treated with H2 regained EEG activity, whereas no recovery was observed in animals treated with placebo. H2 therapy markedly improved intra-resuscitation brain tissue oxygenation and prevented an increase in central venous pressure after ECPR. H2 attenuated an increase in syndecan-1 levels and enhanced an increase in interleukin-10, vascular endothelial growth factor, and leptin levels after ECPR. Metabolomics analysis identified significant changes at 2 h after CA/ECPR between the two groups, particularly in D-glutamine and D-glutamate metabolism. CONCLUSIONS: H2 therapy improved mortality in highly lethal CA rats rescued by ECPR and helped recover brain electrical activity. The underlying mechanism might be linked to protective effects against endothelial damage. Further studies are warranted to elucidate the mechanisms responsible for the beneficial effects of H2 on ischemia-reperfusion injury in critically ill patients who require ECMO support.

BACKGROUND: Despite much evidence supporting the monitoring of the divergence of transcutaneous partial pressure of carbon dioxide (tcPCO2) from arterial partial pressure carbon dioxide (artPCO2) as an indicator of the shock status, data are limited on the relationships of the gradient between tcPCO2 and artPCO2 (tc-artPCO2) with the systemic oxygen metabolism and hemodynamic parameters. Our study aimed to test the hypothesis that tc-artPCO2 can detect inadequate tissue perfusion during hemorrhagic shock and resuscitation. METHODS: This prospective animal study was performed using female pigs at a university-based experimental laboratory. Progressive massive hemorrhagic shock was induced in mechanically ventilated pigs by stepwise blood withdrawal. All animals were then resuscitated by transfusing the stored blood in stages. A transcutaneous monitor was attached to their ears to measure tcPCO2. A pulmonary artery catheter (PAC) and pulse index continuous cardiac output (PiCCO) were used to monitor cardiac output (CO) and several hemodynamic parameters. The relationships of tc-artPCO2 with the study parameters and systemic oxygen delivery (DO2) were analyzed. RESULTS: Hemorrhage and blood transfusion precisely impacted hemodynamic and laboratory data as expected. The tc-artPCO2 level markedly increased as CO decreased. There were significant correlations of tc-artPCO2 with DO2 and COs (DO2: r = - 0.83, CO by PAC: r = - 0.79; CO by PiCCO: r = - 0.74; all P < 0.0001). The critical level of oxygen delivery (DO2crit) was 11.72 mL/kg/min according to transcutaneous partial pressure of oxygen (threshold of 30 mmHg). Receiver operating characteristic curve analyses revealed that the value of tc-artPCO2 for discrimination of DO2crit was highest with an area under the curve (AUC) of 0.94, followed by shock index (AUC = 0.78; P < 0.04 vs tc-artPCO2), and lactate (AUC = 0.65; P < 0.001 vs tc-artPCO2). CONCLUSIONS: Our observations suggest the less-invasive tc-artPCO2 monitoring can sensitively detect inadequate systemic oxygen supply during hemorrhagic shock. Further evaluations are required in different forms of shock in other large animal models and in humans to assess its usefulness, safety, and ability to predict outcomes in critical illnesses.

2020年2月、横浜港に入港したクルーズ船が新型コロナウイルス感染症(COVID-19)の猛威を世界に知らしめたかと思うや否や、2ヵ月後、ニューヨークでは1日に感染者1万人、死者1,000人を記録、世界中を恐怖と混乱に導いた。このような激動の時代から未来を切りひらく希望とは何か。"リサーチマインド"が、そのヒントをわれわれに与えてくれていると考える。本稿では、ニューヨークの救急外来(ER)での診療経験をもとに、リサーチマインドという観点からCOVID-19パンデミックを考察したい。(著者抄録)

Patients with coronavirus disease 2019 (COVID-19) can have increased risk of mortality shortly after intubation. The aim of this study is to develop a model using predictors of early mortality after intubation from COVID-19. A retrospective study of 1945 intubated patients with COVID-19 admitted to 12 Northwell hospitals in the greater New York City area was performed. Logistic regression model using backward selection was applied. This study evaluated predictors of 14-day mortality after intubation for COVID-19 patients. The predictors of mortality within 14 days after intubation included older age, history of chronic kidney disease, lower mean arterial pressure or increased dose of required vasopressors, higher urea nitrogen level, higher ferritin, higher oxygen index, and abnormal pH levels. We developed and externally validated an intubated COVID-19 predictive score (ICOP). The area under the receiver operating characteristic curve was 0.75 (95% CI 0.73-0.78) in the derivation cohort and 0.71 (95% CI 0.67-0.75) in the validation cohort; both were significantly greater than corresponding values for sequential organ failure assessment (SOFA) or CURB-65 scores. The externally validated predictive score may help clinicians estimate early mortality risk after intubation and provide guidance for deciding the most effective patient therapies.

BACKGROUND: Cardiac arrest (CA) results in loss of blood circulation to all tissues leading to oxygen and metabolite dysfunction. Return of blood flow and oxygen during resuscitative efforts is the beginning of reperfusion injury and is marked by the generation of reactive oxygen species (ROS) that can directly damage tissues. The plasma serves as a reservoir and transportation medium for oxygen and metabolites critical for survival as well as ROS that are generated. However, the complicated interplay among various ROS species and antioxidant counterparts, particularly after CA, in the plasma have not been evaluated. In this study, we assessed the equilibrium between pro- and anti-oxidants within the plasma to assess the oxidative status of plasma post-CA. METHODS: In male Sprague-Dawley rats, 10 min asphyxial-CA was induced followed by cardiopulmonary resuscitation (CPR). Plasma was drawn immediately after achieving return of spontaneous circulation (ROSC) and after 2 h post-ROSC. Plasma was isolated and analyzed for prooxidant capacity (Amplex Red and dihydroethidium oxidation, total nitrate and nitrite concentration, xanthine oxidase activity, and iron concentration) and antioxidant capacity (catalase and superoxide dismutase activities, Total Antioxidant Capacity, and Iron Reducing Antioxidant Power Assay). The consequent oxidative products, such as 4-Hydroxyl-2-noneal, malondialdehyde, protein carbonyl, and nitrotyrosine were evaluated to determine the degree of oxidative damage. RESULTS: After CA and resuscitation, two trends were observed: (1) plasma prooxidant capacity was lower during ischemia, but rapidly increased post-ROSC as compared to control, and (2) plasma antioxidant capacity was increased during ischemia, but either decreased or did not increase substantially post-ROSC as compared to control. Consequently, oxidation products were increased post-ROSC. CONCLUSION: Our study evaluated the disbalance of pro- and anti-oxidants after CA in the plasma during the early phase after resuscitation. This disequilibrium favors the prooxidants and is associated with increased levels of downstream oxidative stress-induced end-products, which the body's antioxidant capacity is unable to directly mitigate. Here, we suggest that circulating plasma is a major contributor to oxidative stress post-CA and its management requires substantial early intervention for favorable outcomes.

Abstract We describe the clinical course of a 65-year-old male patient who suffered from hydrocarbon-induced myelodysplasia and was successfully treated with the thrombopoietin receptor agonist (TPO-RA), romiplostim. Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis, cytopenias, and increased risk of leukemic transformation. Here, we present a clinical vignette of MDS-associated thrombocytopenia refractory to first-line drugs as well as the TPO-RA, eltrombopag. To date, romiplostim is an U.S. Food and Drug Administration (FDA)-approved drug for idiopathic thrombocytopenic purpura and thrombocytopenia secondary to liver disease. Of note, currently the FDA advises against its use in MDS based on previous long-term safety concerns. Since the therapeutic options for thrombocytopenia in MDS patients are sparse, repurposing and reassessing romiplostim in this setting have been the focus of recent studies. At the time of writing, no published double-blind randomized clinical trials have conducted a head-to-head comparison between romiplostim and eltrombopag in thrombocytopenic MDS patients. To the best of our knowledge, for a thrombocytopenic patient in the setting of MDS, this is the first documented report of refractory clinical response after a 2-year use of eltrombopag in which replacement of treatment with romiplostim resulted in sustained physiological counts of thrombocytes within four weeks.

Abstract This case report describes a 52-year-old male patient, with the incidental finding of inferior vena cava filter (IVCF) fragments impacted into the right ventricle, secondary to IVCF fragmentation and subsequent embolization. While IVCFs are prescribed to prevent pulmonary embolizations when anticoagulation is either contraindicated, or has failed, IVCF embolizations to the heart represent an extremely rare, but potentially life-threatening complication. Of note, at the time of writing, the utility and effectiveness of IVCF are not fully established. Intracardiac embolizations of IVCF typically present with complications such as hypotension, cardiac tamponade, arrhythmias, ventricle perforation, bleeding, cardiac arrest, and death. To our knowledge, this is the first case report of an asymptomatic kidney transplant recipient found to have right ventricle embolizations of IVCF fragments through routine assessment. Additionally, this is also the first report of an asymptomatic patient who presented IVCF fragments embolized to the right ventricle and left gonadal vein in the same clinical setting.

We compared the outcome of COVID-19 in immunosuppressed solid organ transplant (SOT) patients to a transplant naïve population. In total, 10 356 adult hospital admissions for COVID-19 from March 1, 2020 to April 27, 2020 were analyzed. Data were collected on demographics, baseline clinical conditions, medications, immunosuppression, and COVID-19 course. Primary outcome was combined death or mechanical ventilation. We assessed the association between primary outcome and prognostic variables using bivariate and multivariate regression models. We also compared the primary endpoint in SOT patients to an age, gender, and comorbidity-matched control group. Bivariate analysis found transplant status, age, gender, race/ethnicity, body mass index, diabetes, hypertension, cardiovascular disease, COPD, and GFR <60 mL/min/1.73 m2 to be significant predictors of combined death or mechanical ventilation. After multivariate logistic regression analysis, SOT status had a trend toward significance (odds ratio [OR] 1.29; 95% CI 0.99-1.69, p = .06). Compared to an age, gender, and comorbidity-matched control group, SOT patients had a higher combined risk of death or mechanical ventilation (OR 1.34; 95% CI 1.03-1.74, p = .027).

BACKGROUND: At lower ambient temperature, patients with out-of-hospital cardiac arrest (OHCA) easily experience hypothermia. Hypothermia has shown to improve the rate of successful return of spontaneous circulation (ROSC) in animal models. We hypothesized that lower temperature affects the impact of bystander cardiopulmonary resuscitation (CPR) on the increased odds of a favorable neurological outcome post-OHCA. METHODS: This study used information collected by the prospective, nationwide, Utstein registry to examine data from 352,689 adult patients who experienced OHCA from 2012 to 2016 in Japan. The primary outcome was a 1-month favorable neurological outcomes. Multivariable logistic regression analyses were conducted to test the impact of bystander CPR according to the temperature on the favorable outcome. RESULTS: A total of 201,111 patients with OHCA were included in the complete case analysis. The lower temperature group had lower proportions of receiving bystander CPR (46.5 vs. 47.9%) and having favorable outcome (2.1 vs 2.8%) than those in the higher group. Multivariable analysis revealed that bystander CPR at lower temperatures was significantly associated with favorable outcomes (adjusted odds ratio, 1.22; 95% CI, 1.09-1.37), whereas bystander CPR at higher temperatures was not associated with favorable outcomes (1.02; 0.92-1.13). The nonlinear relationship using a spline curve in the multivariable model revealed that odds ratio of favorable neurological outcomes associated with bystander CPR increased as the temperature decreased. CONCLUSION: Bystander CPR was associated with favorable neurological outcomes at lower temperatures. The odds of a favorable outcome associated with bystander CPR increased as the temperature decreased.

Using a new method for measuring the molecular ratio (R) of inhalation to exhalation, we investigated the effect of high fraction of inspired oxygen (FIO2) on oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ) in mechanically ventilated rats. Twelve rats were equally assigned into two groups by anesthetics: intravenous midazolam/fentanyl vs. inhaled isoflurane. R, VO2, VCO2, and RQ were measured at FIO2 0.3 or 1.0. R error was ± 0.003. R was 1.0099 ± 0.0023 with isoflurane and 1.0074 ± 0.0018 with midazolam/fentanyl. R was 1.0081 ± 0.0017 at an FIO2 of 0.3 and 1.0092 ± 0.0029 at an FIO2 of 1.0. There were no differences in VCO2 among the groups. VO2 increased at FIO2 1.0, which was more notable when midazolam/fentanyl was used (isoflurane-FIO2 0.3: 15.4 ± 1.1; isoflurane-FIO2 1.0: 17.2 ± 1.8; midazolam/fentanyl-FIO2 0.3: 15.4 ± 1.1; midazolam/fentanyl-FIO2 1.0: 21.0 ± 2.2 mL/kg/min at STP). The RQ was lower at FIO2 1.0 than FIO2 0.3 (isoflurane-FIO2 0.3: 0.80 ± 0.07; isoflurane-FIO2 1.0: 0.71 ± 0.05; midazolam/fentanyl-FIO2 0.3: 0.79 ± 0.03; midazolam/fentanyl-FIO2 1.0: 0.59 ± 0.04). R was not affected by either anesthetics or FIO2. Inspired 100% O2 increased VO2 and decreased RQ, which might be more remarkable when midazolam/fentanyl was used.

OBJECTIVE: Reliability of capillary refill time (CRT) has been questionable. The purpose of this study was to examine that a standardized method and clinical experience would improve the reliability of CRT. METHODS: This was a cross-sectional study in the emergency department (ED). Health care providers (HCPs) performed CRT without instruments (method 1) to classify patients as having normal or abnormal (≤2/>2 s) CRT. An ED attending physician quantitatively measured CRT using a chronograph (standardized visual CRT, method 2). A video camera was mounted on top of the hand tool to obtain a digital recording. The videos were used to calculate CRT via image software (image CRT, method 3) as a criterion standard of methods. Additionally, 9 HCPs reviewed the videos in a separate setting in order to visually assess CRT (video CRT, method 4). RESULTS: We enrolled 30 patients in this study. Standardized visual CRT (method 2) identified 10 abnormal patients, while two patients were identified by CRT without instruments (method 1). There was no correlation (κ value, 0.00) between CRT without instruments (method 1) and image CRT (method 3), however the correlation between standardized visual CRT (method 2) and image CRT (method 3) was strong (r = 0.64, p < 0.01). Both intra-observer reliability and correlation coefficient with image CRT (method 3) was higher in video CRT (method 4) by more experienced clinicians. CONCLUSIONS: Visual assessment is variable but a standardized method such as using a chronograph and/or clinical experience may aid clinicians to improve the reliability of visually assessed CRT.

Abstract Organ transplantation can be associated with vascular torsions and angulations of both recipient and donor vessels. Such kinks and/or torsions of vessels can compromise the vascular integrity, obstruct inflow and/or outflow, and result in loss of the organ and/or body parts. On many occasions, mild angulations and torsions can be successfully addressed by repositioning the organ. In cases where the abnormal findings persist, maneuvers such as placing a fat pad to create a smoother curve, or even opening the peritoneum (in the case of kidney transplants) to allow for a better positioning of the organ, are associated with successful outcomes. When such torsions/angulations persist despite these approaches, further innovative tactics are required. In the current report, we propose a technique that involves longitudinally opening of a synthetic graft that is rigid enough to maintain its shape, such as a ringed polytetrafluoroethylene graft, and placing it as an external stent around the angulated/torsioned vessel. This maneuver will correct the underlying vascular compromise without having to perform any further invasive interventions, such as reimplanting the organ or resecting part of the involved vessel. Although primarily illustrated for application by describing an instance in which exostenting was applied during kidney transplantation, our approach could be applied to any vessel under many circumstances where angulations/twists are encountered. In this report, we describe the use of an external stent, also called exostenting, to correct a severe torsion/angulation of the external iliac artery in a kidney transplant recipient where all other measures were unsuccessful.

BACKGROUND: Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. METHODS: We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. RESULTS: Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI-associated myocardial dysfunction after cardiac surgery. CONCLUSION: The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.

Background Cardiac arrest (CA) can induce oxidative stress after resuscitation, which causes cellular and organ damage. We hypothesized that post-resuscitation normoxic therapy would protect organs against oxidative stress and improve oxygen metabolism and survival. We tested the oxygen-sensitive reactive oxygen species from mitochondria to determine the association with hyperoxia-induced oxidative stress. Methods and Results Sprague-Dawley rats were subjected to 10-minute asphyxia-induced CA with a fraction of inspired O2 of 0.3 or 1.0 (normoxia versus hyperoxia, respectively) after resuscitation. The survival rate at 48 hours was higher in the normoxia group than in the hyperoxia group (77% versus 28%, P<0.01), and normoxia gave a lower neurological deficit score (359±140 versus 452±85, P<0.05) and wet to dry weight ratio (4.6±0.4 versus 5.6±0.5, P<0.01). Oxidative stress was correlated with increased oxygen levels: normoxia resulted in a significant decrease in oxidative stress across multiple organs and lower oxygen consumption resulting in normalized respiratory quotient (0.81±0.05 versus 0.58±0.03, P<0.01). After CA, mitochondrial reactive oxygen species increased by ≈2-fold under hyperoxia. Heme oxygenase expression was also oxygen-sensitive, but it was paradoxically low in the lung after CA. In contrast, the HMGB-1 (high mobility group box-1) protein was not oxygen-sensitive and was induced by CA. Conclusions Post-resuscitation normoxic therapy attenuated the oxidative stress in multiple organs and improved post-CA organ injury, oxygen metabolism, and survival. Additionally, post-CA hyperoxia increased the mitochondrial reactive oxygen species and activated the antioxidation system.

Capillary refill time (CRT) is a method of measuring a patient's peripheral perfusion status through a visual assessment performed by a clinician. We developed a new method of measuring CRT using standard pulse oximetry sensor, which was designated capillary refill index (CRI). We evaluated the accuracy of CRI in comparison to CRT image analysis. Thirty healthy adult volunteers were recruited for a derivation study and 30 patients in the emergency department (ED) were for validation. Our high fidelity mechanical device compresses and releases the fingertip to measure changes in blood volume using infrared-light (940 nm). CRT was calculated by image analysis software using recorded fingertip videos. CRI and CRT were measured at: room temperature (ROOM TEMP), 15 °C cold water (COLD), and 38 °C warm water (REWARM). Intra-rater reliability, Bland-Altman plots, and correlation coefficients were used to evaluate the accuracy of the novel CRI method. CRI (4.9 [95% CI 4.5-5.3] s) and CRT (4.0 [3.6-4.3]) in the COLD group were higher than the ROOM TEMP and REWARM groups. High intra-rater reliability was observed in both measurements (0.97 [0.95-0.98] and 0.98 [0.97-0.99], respectively). The Bland-Altman plots suggested a systematic bias: CRI was consistently higher than CRT (difference: + 1.01 s). There was a strong correlation between CRI and CRT (r = 0.89, p < 0.001). ED patients had higher CRI (3.91 [5.05-2.75]) and CRT (2.21 [3.19-1.23]) than those of healthy volunteers at room temperature. The same difference and correlation patterns were verified in the ED setting. CRI was as reliable as CRT by image analysis. The values of CRI was approximately 1 s higher than CRT.

The pituitary gland plays an important endocrinal role, however its damage after cardiac arrest (CA) has not been well elucidated. The aim of this study was to determine a pituitary gland damage induced by CA. Rats were subjected to 10-min asphyxia and cardiopulmonary resuscitation (CPR). Immunohistochemistry and ELISA assays were used to evaluate the pituitary damage and endocrine function. Samples were collected at pre-CA, and 30 and 120 min after cardio pulmonary resuscitation. Triphenyltetrazolium chloride (TTC) staining demonstrated the expansion of the pituitary damage over time. There was phenotypic validity between the pars distalis and nervosa. Both CT-proAVP (pars nervosa hormone) and GH/IGF-1 (pars distalis hormone) decreased over time, and a different expression pattern corresponding to the damaged areas was noted (CT-proAVP, 30.2 ± 6.2, 31.5 ± 5.9, and 16.3 ± 7.6 pg/mg protein, p < 0.01; GH/IGF-1, 2.63 ± 0.61, 0.62 ± 0.36, and 2.01 ± 0.41 ng/mg protein, p < 0.01 respectively). Similarly, the expression pattern between these hormones in the end-organ systems showed phenotypic validity. Plasma CT-proAVP (r = 0.771, p = 0.025) and IGF-1 (r = -0.775, p = 0.024) demonstrated a strong correlation with TTC staining area. Our data suggested that CA induces pathological and functional damage to the pituitary gland.

Background: Identification of the mechanisms underlying mitochondrial dysfunction is key to understanding the pathophysiology of acute injuries such as cardiac arrest (CA); however, effective methods for measurement of mitochondrial function associated with mitochondrial isolation have been debated for a long time. This study aimed to evaluate the dysregulation of mitochondrial respiratory function after CA while testing the sampling bias that might be induced by the mitochondrial isolation method. Materials and Methods: Adult rats were subjected to 10-min asphyxia-induced CA. 30 min after resuscitation, the brain and kidney mitochondria from animals in sham and CA groups were isolated (n = 8, each). The mitochondrial quantity, expressed as protein concentration (isolation yields), was determined, and the oxygen consumption rates were measured. ADP-dependent (state-3) and ADP-limited (state-4) respiration activities were compared between the groups. Mitochondrial quantity was evaluated based on citrate synthase (CS) activity and cytochrome c concentration, measured independent of the isolation yields. Results: The state-3 respiration activity and isolation yield in the CA group were significantly lower than those in the sham group (brain, p < 0.01; kidney, p < 0.001). The CS activity was significantly lower in the CA group as compared to that in the sham group (brain, p < 0.01; kidney, p < 0.01). Cytochrome c levels in the CA group showed a similar trend (brain, p = 0.08; kidney, p = 0.25). Conclusions: CA decreased mitochondrial respiration activity and the quantity of mitochondria isolated from the tissues. Owing to the nature of fragmented or damaged mitochondrial membranes caused by acute injury, there is a potential loss of disrupted mitochondria. Thus, it is plausible that the mitochondrial function in the acute-injury model may be underestimated as this loss is not considered.

Adrenaline is an important pharmacologic treatment during cardiac arrest (CA) for resuscitation. Recent studies suggest that adrenaline increases the likelihood of return of spontaneous circulation (ROSC) but does not contribute to improving neurological outcomes of CA. The mechanisms have not been elucidated yet. A bimodal increase in mean arterial pressure (MAP) is observed after adrenaline injection in rodent CA models [17]. In this study, we focused on alteration of systemic arterial pressure in conjunction with the measurement of cerebral blood oxygenation (CBO) such as oxyhemoglobin (Oxy-Hb), deoxyhemoglobin (Deoxy-Hb), and tissue oxygenation index (TOI) by near-infrared spectroscopy (NIRS). Male Sprague-Dawley rats were used. We attached NIRS between the nasion and the upper cervical spine. Rats underwent 10-minute asphyxia to induce CA. Then, cardiopulmonary resuscitation (CPR) was started, followed by a 20 μg/kg of bolus adrenaline injection at 30 seconds of CPR. This injection accelerated the first increase in MAP, and ROSC was observed with an abrupt increase in CBO. Interestingly, the second increase in MAP, once it exceeded a certain value, was accompanied by paradoxical decreases of Oxy-Hb and TOI, while Deoxy-Hb increased. Based on this finding, we compared Oxy-Hb, Deoxy-Hb, and TOI at the first MAP ≈ 100 mmHg and the second MAP ≈ 100 mmHg. The average of Oxy-Hb and TOI from the 13 animals significantly decreased at the second increase in MAP over 100 mmHg, while Deoxy-Hb significantly increased. NIRS identified a decrease in Oxy-Hb after ROSC. These findings may be a clue to understanding the mechanism of how and why adrenaline alters the neurological outcomes of CA post-resuscitation.

Cerebral hyperperfusion syndrome (CHS) is a rare but fatal perioperative complication after surgical correction of carotid stenosis. Despite numerous treatment options for preventing CHS, it does occur in some patients. We developed the outlet gate technique (OGT), in which the embolic balloon was deflated gradually in accordance with the ratio of oxygen saturation measured by a brain oximeter of the ipsilateral brain region to that in the contralateral region. Between June 2017 and May 2018, 39 patients with carotid stenosis underwent endovascular carotid revascularization procedures; of these, 20 underwent the procedure with the OGT. CBO was measured five times in those 20 patients: before the procedure, with the embolic protection device (EPD) on, with the EPD off, during the procedure, and after the procedure. Preventive treatment options were used more frequently in these patients, and although their surgical status seemed more complicated, perioperative complications were not increased. There were almost significant differences between CBO values except between those during and after the procedure with the OGT. This showed that the OGT allowed for stabilization of the CBO and thus has the potential to prevent CHS.

The real-time evaluation of chest compression during cardiopulmonary resuscitation is important to increase the chances of survival from a cardiac arrest (CA). In addition, cerebral oxygen level measured by near-infrared spectroscopy (NIRS) plays an important role as an indicator of return of spontaneous circulation. Recently, we developed a new method to improve the quality of chest compression using a thoracic pump in conjunction with the classic cardiac pump in a rat asphyxia CA model. This study evaluated the quality of chest compression using NIRS in male Sprague-Dawley rats. NIRS was attached between the nasion and the upper cervical spine, and rats underwent 10 minute asphyxia CA. After CA, we alternately performed three different types of chest compression (cardiac, thoracic, and cardiac plus thoracic pumps) every 30 seconds for up to 4 and a half minutes. We measured the oxyhemoglobin (Oxy-Hb), deoxyhemoglobin (Deoxy-Hb), and tissue oxygenation index (TOI) and compared these values between the groups. Oxy-Hb was significantly different among the groups (cardiac, thoracic, and cardiac plus thoracic, 1.5 ± 0.9, 4.4 ± 0.7, and 5.9 ± 2.1 μmol/L, p < 0.01, respectively), while Deoxy-Hb and TOI were not (Deoxy-HB -2.7 ± 1.2, -1.1 ± 3.2, and -1.6 ± 10.1 μmol/L; TOI, 1.8 ± 1.8, 5.5 ± 1.3, and 9.5 ± 8.0%, respectively). Oxy-Hb showed potential to evaluate the quality of chest compression in a rat asphyxia CA model.

Adrenaline is an important pharmacologic treatment during cardiac arrest (CA) for resuscitation. Recent studies suggest that adrenaline increases the likelihood of return of spontaneous circulation (ROSC) but does not contribute to improving neurological outcomes of CA. The mechanisms have not been elucidated yet. A bimodal increase in mean arterial pressure (MAP) is observed after adrenaline injection in rodent CA models (Okuma et al. Intensive Care Med Exp 7(1), 2019). In this study, we focused on alteration of systemic arterial pressure in conjunction with the measurement of cerebral blood oxygenation (CBO) such as oxyhemoglobin (Oxy-Hb), deoxyhemoglobin (Deoxy-Hb), and tissue oxygenation index (TOI) by near-infrared spectroscopy (NIRS). Male Sprague-Dawley rats were used. We attached NIRS between the nasion and the upper cervical spine. Rats underwent 10 minute asphyxia to induce CA. Then, cardiopulmonary resuscitation (CPR) was started, followed by a 20 μg/kg of bolus adrenaline injection at 30 seconds of CPR. This injection accelerated the first increase in MAP, and ROSC was observed with an abrupt increase in CBO. Interestingly, the second increase in MAP, once it exceeded a certain value, was accompanied by paradoxical decreases of Oxy-Hb and TOI while Deoxy-Hb increased. Based on this finding, we compared Oxy-Hb, Deoxy-Hb, and TOI at the first MAP ≈ 100 mmHg and the second MAP ≈ 100 mmHg. The average of Oxy-Hb and TOI from the 13 animals significantly decreased at the second increase in MAP over 100 mmHg while Deoxy-Hb significantly increased. NIRS identified a decrease in Oxy-Hb after ROSC. These findings may be a clue in understanding the mechanism of how and why adrenaline alters the neurological outcomes of CA post resuscitation.

Clinical investigators have focused on the real-time evaluation of cerebral blood oxygenation (CBO) by near-infrared spectroscopy (NIRS) during cardiopulmonary resuscitation (CPR). A previous study showed that an abrupt increase of oxy-hemoglobin (Hb) level and tissue oxygenation index (TOI) was associated with the timing of return of spontaneous circulation (ROSC). However, it is not clear how TOI alters before and after CPR including a period of cardiac arrest (CA). Therefore, this study aimed to assess CBO with asphyxia CA and its association with CPR to ROSC in rats. Male Sprague-Dawley rats were used. We attached NIRS (NIRO-200NX, Hamamatsu Photonics, Japan) from the nasion to the upper cervical spine in rats. A ten-minute asphyxia was given to induce CA. After CA, mechanical ventilation was restarted, and manual CPR was performed. We examined the mean arterial pressure (MAP), end-tidal carbon dioxide (ETCO2), and Oxy/Deoxy-Hb and TOI. Out of 14 rats, 11 obtained sustained ROSC. After the induction of asphyxia, a rapid drop of TOI was observed, followed by a subsequent increase of Oxy-Hb, Deoxy-Hb, and TOI with CPR. Recent CPR guidelines suggest the use of ETCO2 during CPR since its abrupt increase is a reasonable indicator of ROSC. In this study, abrupt increases in MAP, ETCO2, and TOI were observed at the time of ROSC. TOI can be an alternative to ETCO2 for identifying ROSC after CA, and it also has the capability of monitoring CBO during and after CPR.

This case series reviews four critically ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [coronavirus disease 2019 (COVID-19)] suffering from pneumatosis intestinalis (PI) during their hospital admission. All patients received the biological agent tocilizumab (TCZ), an interleukin (IL)-6 antagonist, as an experimental treatment for COVID-19 before developing PI. COVID-19 and TCZ have been independently linked to PI risk, yet the cause of this relationship is unknown and under speculation. PI is a rare condition, defined as the presence of gas in the intestinal wall, and although its pathogenesis is poorly understood, intestinal ischemia is one of its causative agents. Based on COVID-19's association with vasculopathic and ischemic insults, and IL-6's protective role in intestinal epithelial ischemia-reperfusion injury, an adverse synergistic association of COVID-19 and TCZ can be proposed in the setting of PI. To our knowledge, this is the first published, single center, case series of pneumatosis intestinalis in COVID-19 patients who received tocilizumab therapy.

Purpose: Portable chest radiographs are diagnostically indispensable in intensive care units (ICU). This study aimed to determine if the proposed machine learning technique increased in accuracy as the number of radiograph readings increased and if it was accurate in a clinical setting. Methods: Two independent data sets of portable chest radiographs (n = 380, a single Japanese hospital; n = 1,720, The National Institution of Health [NIH] ChestX-ray8 dataset) were analyzed. Each data set was divided training data and study data. Images were classified as atelectasis, pleural effusion, pneumonia, or no emergency. DenseNet-121, as a pre-trained deep convolutional neural network was used and ensemble learning was performed on the best-performing algorithms. Diagnostic accuracy and processing time were compared to those of ICU physicians. Results: In the single Japanese hospital data, the area under the curve (AUC) of diagnostic accuracy was 0.768. The area under the curve (AUC) of diagnostic accuracy significantly improved as the number of radiograph readings increased from 25 to 100% in the NIH data set. The AUC was higher than 0.9 for all categories toward the end of training with a large sample size. The time to complete 53 radiographs by machine learning was 70 times faster than the time taken by ICU physicians (9.66 s vs. 12 min). The diagnostic accuracy was higher by machine learning than by ICU physicians in most categories (atelectasis, AUC 0.744 vs. 0.555, P < 0.05; pleural effusion, 0.856 vs. 0.706, P < 0.01; pneumonia, 0.720 vs. 0.744, P = 0.88; no emergency, 0.751 vs. 0.698, P = 0.47). Conclusions: We developed an automatic detection system for portable chest radiographs in ICU setting; its performance was superior and quite faster than ICU physicians.

This case report describes a 60 year-old Black-American male with a past medical history of human immunodeficiency virus (HIV) infection and hyperthyroidism, who suffered a bilateral spontaneous pneumothorax (SP) in the setting of coronavirus disease 2019 (COVID-19) pneumonia. SP is a well-established complication in HIV-positive patients and only recently has been associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. While HIV and COVID-19 infections have been independently linked with increased risk of SP development, it is unknown if both infections interact in a synergistic fashion to exacerbate SP risk. According to the Centers for Disease Control and Prevention (CDC), patients living with HIV have a higher risk of developing severe COVID-19 infection and the mechanism remains to be elucidated. To the best of our knowledge, this is the first report of a HIV-positive patient, who in the setting of SARS-CoV-2 infection, developed bilateral apical spontaneous pneumothorax and was later found to have a left lower lobe tension pneumothorax. This case highlights the importance of considering SP on the differential diagnosis when HIV-positive patients suddenly develop respiratory distress in the setting of SARS-CoV-2 infection.

Abstract In this case report, we describe the clinical course of a complicated transplant renal artery (TRA) pseudoaneurysm, clinically featured by gross and massive hematuria one month after a kidney transplant was performed on a 50 year-old male patient. TRA pseudoaneurysm is a rare but potentially life-threatening complication that may result in bleeding, infection, graft dysfunction/loss, lower limb ischemia/loss, hemorrhagic shock, and death. TRA pseudoaneurysm treatment remains challenging as it needs to be tailored to the patient characteristics including hemodynamic stability, graft function, anatomy, presentation, and pseudoaneurysm features. This publication discusses the clinical scenario of massive gross hematuria that derived from a retroperitoneal hematoma which originated from an actively bleeding TRA pseudoaneurysm. This case highlights the combined approach of endovascular stent placement and subsequent transplant nephrectomy as a last resort in the management of intractable bleeding from a complicated TRA pseudoaneurysm. To the best of our knowledge, this is the first published case report of an actively bleeding TRA anastomotic pseudoaneurysm that caused a massive retroperitoneal bleed that in turn evacuated via the bladder after disrupting the ureter-to-bladder anastomosis. A temporizing hemostatic arterial stent placed percutaneously allowed for a safer and controlled emergency transplant nephrectomy.

OBJECTIVE: A 12-lead electrocardiogram (ECG) is the standard of care for chest pain patients. However, 12-lead ECGs have difficulty detecting ischemia of the right ventricle or posterior wall of the heart. New technology exists to mathematically synthesize these leads from a 12-lead ECG; however, this technology has not been evaluated in the emergency department (ED). We assessed the level of agreement between synthesized 18-lead ECGs and actual 18-lead ECGs in identifying ST elevations, ST depressions, and T wave inversions in ED patients. METHODS: Actual 12- and 18-lead ECGs were acquired and synthesized 18-lead ECGs were produced based on waveforms from 12-lead ECGs. A blinded cardiologist interpreted the actual and synthesized 18-lead ECGs to identify the presence of abnormalities. Using actual 18-lead ECGs as the reference, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa of synthesized 18-lead ECGs in identifying abnormalities were determined. RESULTS: Data from 295 patients were analyzed. There was 100% agreement between synthesized 18-lead ECGs and actual 18-lead ECGs in identifying ST elevations and ST depressions (sensitivity, specificity, PPV, and NPV of 100%, and kappa of 1.00). Synthesized 18-lead ECGs had 95% sensitivity, 80% specificity, 97% PPV, and 70% NPV in identifying T wave inversions, when compared with actual 18-lead ECGs (kappa: 0.70). CONCLUSION: Synthesized 18-lead ECGs demonstrated 100% agreement with actual 18-lead ECGs in the identification of ST elevations and ST depressions and good agreement in the identification of T wave inversions in a sample of patients ED patients with complaints suspicious of cardiac origin.

INTRODUCTION: Quality improvement in the administration of extracorporeal cardiopulmonary resuscitation (ECPR) over time and its association with low-flow duration (LFD) and outcomes of cardiac arrest (CA) have been insufficiently investigated. In this study, we hypothesized that quality improvement in efforts to shorten the duration of initiating ECPR had decreased LFD over the last 15 years of experience at an academic tertiary care hospital, which in turn improved the outcomes of in-hospital CA (IHCA). METHODS: This was a single-center retrospective observational study of ECPR patients between January 2003 and December 2017. A rapid response system (RRS) and an extracorporeal membrane oxygenation (ECMO) program were initiated in 2011 and 2013. First, the association of LFD per minute with the 90-day mortality and neurological outcome was analyzed using multiple logistic regression analysis. Then, the temporal changes in LFD were investigated. RESULTS: Of 175 study subjects who received ECPR, 117 had IHCA. In the multivariate logistic regression, IHCA patients with shorter LFD experienced significantly increased 90-day survival and favorable neurological outcomes (LFD per minute, 90-day survival: odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.94-1.00, P = 0.032; 90-day favorable neurological outcome: OR = 0.97, 95% CI = 0.94-1.00, P = 0.049). In the study period, LFD significantly decreased over time (slope - 5.39 [min/3 years], P < 0.0001). CONCLUSION: A shorter LFD was associated with increased 90-day survival and favorable neurological outcomes of IHCA patients who received ECPR. The quality improvement in administering ECPR over time, including the RRS program and the ECMO program, appeared to ameliorate clinical outcomes.

OBJECTIVE: Develop an automated approach to detect flash (<1.0 s) or prolonged (>2.0 s) capillary refill time (CRT) that correlates with clinician judgment by applying several supervised machine learning (ML) techniques to pulse oximeter plethysmography data. MATERIALS AND METHODS: Data was collected in the Pediatric Intensive Care Unit (ICU), Cardiac ICU, Progressive Care Unit, and Operating Suites in a large academic children's hospital. Ninety-nine children and 30 adults were enrolled in testing and validation cohorts, respectively. Patients had 5 paired CRT measurements by a modified pulse oximeter device and a clinician, generating 485 waveform pairs for model training. Supervised ML models using gradient boosting (XGBoost), logistic regression (LR), and support vector machines (SVMs) were developed to detect flash (<1 s) or prolonged CRT (≥2 s) using clinician CRT assessment as the reference standard. Models were compared using Area Under the Receiver Operating Curve (AUC) and precision-recall curve (positive predictive value vs. sensitivity) analysis. The best performing model was externally validated with 90 measurement pairs from adult patients. Feature importance analysis was performed to identify key waveform characteristics. RESULTS: For flash CRT, XGBoost had a greater mean AUC (0.79, 95% CI 0.75-0.83) than logistic regression (0.77, 0.71-0.82) and SVM (0.72, 0.67-0.76) models. For prolonged CRT, XGBoost had a greater mean AUC (0.77, 0.72-0.82) than logistic regression (0.73, 0.68-0.78) and SVM (0.75, 0.70-0.79) models. Pairwise testing showed statistically significant improved performance comparing XGBoost and SVM; all other pairwise model comparisons did not reach statistical significance. XGBoost showed good external validation with AUC of 0.88. Feature importance analysis of XGBoost identified distinct key waveform characteristics for flash and prolonged CRT, respectively. CONCLUSION: Novel application of supervised ML to pulse oximeter waveforms yielded multiple effective models to identify flash and prolonged CRT, using clinician judgment as the reference standard. TWEET: Supervised machine learning applied to pulse oximeter waveform features predicts flash or prolonged capillary refill.

Measures of peripheral perfusion can be used to assess the hemodynamic status of critically ill patients. By monitoring peripheral perfusion status, clinicians can promptly initiate life-saving therapy and reduce the likelihood of shock-associated death. Historically, abnormal perfusion has been indicated by the observation of pale, cold, and clammy skin with increased capillary refill time. The utility of these assessments has been debated given that clinicians may vary in their clinical interpretation of body temperature and refill time. Considering these constraints, current sepsis bundles suggest the need to revise resuscitation guidelines. New technologies have been developed to calculate capillary refill time in the hopes of identifying a new gold standard for clinical care. These devices measure either light reflected at the surface of the fingertip (reflected light), or light transmitted through the inside of the fingertip (transmitted light). These new technologies may enable clinicians to monitor peripheral perfusion status more accurately and may increase the potential for ubiquitous hemodynamic monitoring across different clinical settings. This review will summarize the different methods available for peripheral perfusion monitoring and will discuss the advantages and disadvantages of each approach.

Despite recent advances in the management of post-cardiac arrest syndrome (PCAS), the survival rate, without neurologic sequelae after resuscitation, remains very low. Whole-body ischemia, followed by reperfusion after cardiac arrest (CA), contributes to PCAS, for which established pharmaceutical interventions are still lacking. It has been shown that a number of different processes can ultimately lead to neuronal injury and cell death in the pathology of PCAS, including vasoconstriction, protein modification, impaired mitochondrial respiration, cell death signaling, inflammation, and excessive oxidative stress. Recently, the pathophysiological effects of inhaled gases including nitric oxide (NO), molecular hydrogen (H2), and xenon (Xe) have attracted much attention. Herein, we summarize recent literature on the application of NO, H2, and Xe for treating PCAS. Recent basic and clinical research has shown that these gases have cytoprotective effects against PCAS. Nevertheless, there are likely differences in the mechanisms by which these gases modulate reperfusion injury after CA. Further preclinical and clinical studies examining the combinations of standard post-CA care and inhaled gas treatment to prevent ischemia-reperfusion injury are warranted to improve outcomes in patients who are being failed by our current therapies.

BACKGROUND: High-quality cardiopulmonary resuscitation (HQ-CPR) is of paramount importance to improve neurological outcomes of cardiac arrest (CA). The purpose of this study was to evaluate chest compression methods by combining two theories: cardiac and thoracic pumps. METHODS: Male Sprague-Dawley rats were used. Three types of chest compression methods were studied. The 1-side method was performed vertically with 2 fingers over the sternum. The 2-side method was performed horizontally with 2 fingers, bilaterally squeezing the chest wall. The 3-side method combined the 1-side and the 2-side methods. Rats underwent 10 min of asphyxial CA. We examined ROSC rates, the left ventricular functions, several arterial pressures, intrathoracic pressure, and brain tissue oxygen. RESULTS: The 3-side group achieved 100% return of spontaneous circulation (ROSC) from asphyxial CA, while the 1-side group and 2-side group achieved 80% and 60% ROSC, respectively. Three-side chest compression significantly shortened the time for ROSC among the groups (1-side, 105 ± 36.0; 2-side, 141 ± 21.7; 3-side, 57.8 ± 12.3 s, respectively, P < 0.05). Three-side significantly increased the intrathoracic pressure (esophagus, 7.6 ± 1.9, 7.3 ± 2.8, vs. 12.7 ± 2.2; mmHg, P < 0.01), the cardiac stroke volume (the ratio of the baseline 1.2 ± 0.6, 1.3 ± 0.1, vs. 2.1 ± 0.6, P < 0.05), and the common carotid arterial pressure (subtracted by femoral arterial pressure 4.0 ± 2.5, 0.3 ± 1.6, vs. 8.4 ± 2.6; mmHg, P < 0.01). Three-side significantly increased the brain tissue oxygen (the ratio of baseline 1.4±0.1, 1.3±0.2, vs. 1.6 ± 0.04, P < 0.05). CONCLUSIONS: These results suggest that increased intrathoracic pressure by 3-side CPR improves the cardiac output, which may in turn help brain oxygenation during CPR.

Background Cardiac arrest (CA) has been a leading cause of death for many decades. Despite years of research, we still do not understand how each organ responds to the reintroduction of blood flow after prolonged CA. Following changes in metabolites of individual organs after CA and resuscitation gives context to the efficiency and limitations of current resuscitation protocols. Methods and Results Adult male Sprague-Dawley rats were arbitrarily assigned into 3 groups: control, 20 minutes of CA, or 20 minutes of CA followed by 30 minutes of cardiopulmonary bypass resuscitation. The rats were euthanized by decapitation to harvest brain, heart, kidney, and liver tissues. The obtained tissue samples were analyzed by ultra-high-performance liquid chromatography-high-accuracy mass spectrometry for comprehensive metabolomics evaluation. After resuscitation, the brain showed decreased glycolysis metabolites and fatty acids and increased amino acids compared with control. Similarly, the heart displayed alterations mostly in amino acids. The kidney showed decreased amino acid and fatty acid pools with severely increased tricarboxylic acid cycle metabolites following resuscitation, while the liver showed minimal alterations with slight changes in the lipid pool. Each tissue has a distinct pattern of metabolite changes after ischemia/reperfusion. Furthermore, resuscitation worsens the metabolic dysregulation in the brain and kidney, while it normalizes metabolism in the heart. Conclusions Developing metabolic profiles using a global metabolome analysis identifies the variable nature of metabolites in individual organs after CA and reperfusion, establishing a stark contrast between the normalized heart and liver and the exacerbated brain and kidney, only after the reestablishment of blood circulation.

Capillary refill time has been accepted as a method to manually assess a patient's peripheral blood perfusion. Recently, temperature has been reported to affect capillary refill time and therefore temperature may interfere with accurate bedside peripheral blood perfusion evaluation. We applied a new method of analysis that uses standard hospital pulse oximetry equipment and measured blood refill time in order to test whether lowered fingertip temperature alters peripheral blood perfusion. Thirty adult healthy volunteers of differing races (skin colors) and age (young: 18-49 years and old: ≥ 50 years) groups were recruited. We created a high fidelity mechanical device to compress and release the fingertip and measure changes in blood volume using infrared light (940 nm). Capillary refill times were measured at the fingertip at three different temperature settings: ROOM TEMPERATURE, COLD by 15 °C cold water, and REWARM by 38 °C warm water. The COLD group has decreased fingertip temperature (23.6 ± 3.6 °C) and increased blood refill time (4.67 s [95% CI 3.57-5.76], p < 0.001). This was significantly longer than ROOM TEMPERATURE (1.96 [1.60-2.33]) and REWARM (1.96 [1.73-2.19]). Blood refill time in older subjects tended to be longer than in younger subjects (2.28 [1.61-2.94] vs. 1.65 [1.36-1.95], p = 0.077). There was a negative correlation (r = - 0.471, p = 0.009) between age and temperature. A generalized linear mixed-effects model revealed that lower temperature (OR 0.63 [95% CI 0.61-0.65], p < 0.001) rather than age (OR 1.00 [0.99-1.01], p = 0.395) was the independent factor most associated with increased blood refill time. Lowered fingertip temperatures significantly increase blood refill time which then returns to baseline when the fingertip is rewarmed. In our limited number of population, we did not find an association with age after the adjustment for the fingertip temperature.

BACKGROUND: Cardiac arrest is one of the leading causes of death with a very high mortality rate. No therapeutic drug that can be administered during resuscitation has been reported. Mitochondrial dysfunction is believed to play an important role for the pathogenesis of cardiac arrest. SS-31, a tetra-peptide, has been shown to protect mitochondria from ischaemia/reperfusion injury. Therefore, we tested whether SS-31 improves rat survival after prolonged cardiac arrest. METHODS: Rats were randomised into two groups. After 25minutes of asphyxia-induced cardiac arrest, rats were resuscitated with or without SS-31 using cardiopulmonary bypass resuscitation. Rat survival was followed for additional 4.5hours using haemodynamic monitoring. The blood gas was analysed for surviving rats at multiple time points. RESULTS AND CONCLUSIONS: After 5hours, 5 of 10 rats survived in the SS-31 group whereas only 1 of 10 rats survived in the control group (p=0.026). At 90minutes after resuscitation, the blood lactate level in the SS-31 treated rats (4.29±2.5mmol/L) was significantly lower than in control rats (7.36±3.1mmol/L, p=0.026), suggesting mitochondrial aerobic respiration was improved with SS-31 treatment. Overall, our data show the potential of SS-31 as a novel therapeutic in cardiac arrest.

BACKGROUND: Traditional capillary refill time (CRT) is a manual measurement that is commonly used by clinicians to identify deterioration in peripheral perfusion status. Our study compared a novel method of measuring peripheral perfusion using an investigational device with standardized visual CRT and tested the clinical usefulness of this investigational device, using an existing pulse oximetry sensor, in an emergency department (ED) setting. MATERIAL AND METHODS: An ED attending physician quantitatively measured CRT using a chronometer (standardized visual CRT). The pulse oximetry sensor was attached to the same hand. Values obtained using the device are referred to as blood refill time (BRT). These techniques were compared in its numbers with the Bland-Altman plot and the predictability of patients' admissions. RESULTS: Thirty ED patients were recruited. Mean CRT of ED patients was 1.9 ± 0.8 s, and there was a strong correlation with BRT (r = 0.723, p < 0.001). The Bland-Altman plot showed a proportional bias pattern. The ED physician identified 3 patients with abnormal CRT (> 3 s). Area under the receiver operator characteristic curve (AUC) of BRT to predict whether or not CRT was greater than 3 s was 0.82 (95% CI, 0.58-1.00). Intra-rater reliability of BRT was 0.88 (95% CI, 0.79-0.94) and that of CRT was 0.92 (0.85-0.96). Twelve patients were admitted to the hospital. AUC to predict patients' admissions was 0.67 (95% CI, 0.46-0.87) by BRT and 0.76 (0.58-0.94) by CRT. CONCLUSIONS: BRT by a pulse oximetry sensor was an objective measurement as useful as the standardized CRT measured by the trained examiner with a chronometer at the bedside.

Ischemic brain damage is the major cause of mortality in cardiac arrest (CA). However, the molecular mechanism responsible for brain damage is not well understood. We previously found that mitochondrial state-3 respiration, which had been decreased following CA, was recovered in the kidney and liver, but not in the brain following cardiopulmonary bypass (CPB) resuscitation. Examination of mitochondria from these tissues may shed light on why the brain is the most vulnerable. In this study, adult male Sprague-Dawley rats were subjected to asphyxia-induced CA for 30 min or 30 min followed by 60 min CPB resuscitation. Mitochondria were then isolated from brain, heart, kidney, and liver tissues for examination using spectrophotometry and mass spectrometry to measure the activities of mitochondrial electron transport complexes and the cardiolipin content. We found significantly decreased complex I activity in mitochondria isolated from all four organs following CA, while complex III and IV activities remained intact. Following CPB resuscitation, complex I activity was normalized in kidney and liver, but unrecovered in brain and heart mitochondria. In addition, complex III activity in brain mitochondria was decreased by 22% with a concomitant decrease in cardiolipin following CPB resuscitation. These results suggest that of the tissues tested only brain mitochondria suffer reperfusion injury in addition to ischemic alterations, resulting in diminished overall mitochondrial respiration following resuscitation.

Phospholipids content in cellular and mitochondrial membranes is essential for maintaining normal function. Previous studies have found a lower polyunsaturated fatty acid (PUFA) content in mitochondria than whole tissue, theorizing decreased PUFA protects against oxidative injury. However, phospholipids (PPLs) are uniquely difficult to quantify without class separation and, as prior approaches have predominately used reverse-phase HPLC or shotgun analysis, quantitation of PPL classes may have been complicated due to the existence of numerous isobaric and isomeric species. We apply normal-phase HPLC with class separation to compare whole tissue and mitochondrial PPL profiles in rat brain, heart, kidney, and liver. In addition, we establish a novel method to ascertain PPL origin, using cardiolipin as a comparator to establish relative cardiolipin /PPL ratios. We report a higher PUFA content in tissue mitochondria driven by increased phosphatidylcholine unsaturation, suggesting mitochondria purposefully incorporate higher PUFA PPLs.

BACKGROUND: The concept that resuscitation from cardiac arrest (CA) results in a metabolic injury is broadly accepted, yet patients never receive this diagnosis. We sought to find evidence of metabolic injuries after CA by measuring O2 consumption and CO2 production (VCO2) in a rodent model. In addition, we tested the effect of inspired 100% O2 on the metabolism. METHODS AND RESULTS: Rats were anesthetized and randomized into 3 groups: resuscitation from 10-minute asphyxia with inhaled 100% O2 (CA-fraction of inspired O2 [FIO2] 1.0), with 30% O2 (CA-FIO2 0.3), and sham with 30% O2 (sham-FIO2 0.3). Animals were resuscitated with manual cardiopulmonary resuscitation. The volume of extracted O2 (VO2) and VCO2 were measured for a 2-hour period after resuscitation. The respiratory quotient (RQ) was RQ=VCO2/VO2. VCO2 was elevated in CA-FIO2 1.0 and CA-FIO2 0.3 when compared with sham-FIO2 0.3 in minutes 5 to 40 after resuscitation (CA-FIO2 1.0: 16.7±2.2, P<0.01; CA-FIO2 0.3: 17.4±1.4, P<0.01; versus sham-FIO2 0.3: 13.6±1.1 mL/kg per minute), and then returned to normal. VO2 in CA-FIO2 1.0 and CA-FIO2 0.3 increased gradually and was significantly higher than sham-FIO2 0.3 2 hours after resuscitation (CA-FIO2 1.0: 28.7±6.7, P<0.01; CA-FIO2 0.3: 24.4±2.3, P<0.01; versus sham-FIO2 0.3: 15.8±2.4 mL/kg per minute). The RQ of CA animals persistently decreased (CA-FIO2 1.0: 0.54±0.12 versus CA-FIO2 0.3: 0.68±0.05 versus sham-FIO2 0.3: 0.93±0.11, P<0.01 overall). CONCLUSIONS: CA altered cellular metabolism resulting in increased VO2 with normal VCO2. Normal VCO2 suggests that the postresuscitation Krebs cycle is operating at a presumably healthy rate. Increased VO2 in the face of normal VCO2 suggests a significant alteration in O2 utilization in postresuscitation. Several RQ values fell well outside the normally cited range of 0.7 to 1.0. Higher FIO2 may increase VO2, leading to even lower RQ values.

It is commonly accepted that brain phospholipids are highly enriched with long-chain polyunsaturated fatty acids (PUFAs). However, the evidence for this remains unclear. We used HPLC-MS to analyze the content and composition of phospholipids in rat brain and compared it to the heart, kidney, and liver. Phospholipids typically contain one PUFA, such as 18:2, 20:4, or 22:6, and one saturated fatty acid, such as 16:0 or 18:0. However, we found that brain phospholipids containing monounsaturated fatty acids in the place of PUFAs are highly elevated compared to phospholipids in the heart, kidney, and liver. The relative content of phospholipid containing PUFAs is ~ 60% in the brain, whereas it is over 90% in other tissues. The most abundant species of phosphatidylcholine (PC) is PC(16:0/18:1) in the brain, whereas PC(18:0/20:4) and PC(16:0/20:4) are predominated in other tissues. Moreover, several major species of plasmanyl and plasmenyl phosphatidylethanolamine are found to contain monounsaturated fatty acid in the brain only. Overall, our data clearly show that brain phospholipids are the least enriched with PUFAs of the four major organs, challenging the common belief that the brain is highly enriched with PUFAs.

Background: Initial blood ammonia level is associated with neurologic outcomes in out-of-hospital cardiac arrest (OHCA). We tested the usefulness of blood ammonia for prediction of long-term neurological outcome of OHCA.Methods and Results: A total of 3,011 hospitalized adult OHCA patients were enrolled. Blood samples were obtained at the ED. Cut-offs (ammonia <100 mu mol/L and lactate <12 mmol/L) were determined in a previous study. Neurological outcomes in survivors were assessed at 3 months. A logistic regression model with adjustment for within-hospital clustering and other risk factors was used to evaluate the association between biomarkers and outcomes. Of 3,011 patients, 380 (13.8%) had favorable neurological outcomes. Ammonia and lactate predicted neurological outcome with an AUC of 0.80 (95% CI: 0.76-0.84) and 0.77 (95% CI: 0.72-0.82), respectively. Adjusted OR for ammonia <100 mu mol/L (4.55; 95% CI: 2.67-7.81) was higher than that for lactate <12 mmol/L (2.63; 95% CI: 1.61-4.28) and most other risk factors, such as cardiac etiology (3.47; 95% CI: 2.55-4.72), age <80 years (3.16; 95% CI: 2.17-4.61), bystander CPR (2.39; 95% CI: 1.70-3.38), and initial rhythm shockable (1.66; 95% CI: 1.16-2.37). The combination of ammonia and lactate had an increased predictive value (AUC, 0.86; 95% CI: 0.85-0.87) compared with that without biomarkers (AUC, 0.81; 95% CI: 0.80-0.82).Conclusions: Initial blood ammonia level is as useful as other traditional prognostic indicators such as lactate. Measurement of both initial blood ammonia and lactate helped accurately predict neurological outcomes after OHCA.

AIMS: The potential of a lysophosphatidylinositol species, LPI(18:0), as a biomarker of ischaemia was tested using a rat model of cardiac arrest (CA). METHODS: Male Sprague-Dawley rats were subjected to asphyxia-induced CA or CA followed by cardiopulmonary bypass (CPB) resuscitation. The brain, heart, kidney and liver tissues were harvested from rats after 0, 5, 10, 20, 30 and 60 min CA and 30 min CA followed by 60 min CPB resuscitation. Blood samples were collected from inferior vena cava and hepatic veins following 30 min CA. Phospholipids were extracted from the four tissues and blood and analysed by HPLC-MS. RESULTS: The relative content of LPI(18:0) compared to a phosphatidylinositol species, PI(18:0,22:4), was significantly increased in the brain, heart, liver and kidney following 30 min CA and decreased following CPB resuscitation. In addition, the increase of the LPI(18:0)/PI(18:0,22:4) ratio in the four tissues was proportional to the duration of ischaemia for CA lasting up to 60 min. The ratio was also found to be increased in plasma from the hepatic vein following 30 min CA. CONCLUSION: LPI(18:0) is a good indicator of CA downtime and has a potential to be used for early prognostication of outcome in CA.

BACKGROUND: It is not yet clear whether hemofiltration can reduce blood cytokine levels sufficiently to benefit patients who suffer prolonged cardiac arrest (CA) treated with cardiopulmonary bypass (CPB). We sought to assess effects of high-volume and standard volume continuous veno-venous hemofiltration (CVVH) on blood cytokine levels and survival in a rat model of prolonged CA treated with CPB. METHODS: Sprague-Dawley male rats were subjected to 12 min of asphyxia to induce CA. CPB was initiated for resuscitation of animals and maintained for 30 min. Twenty-four rats were randomly assigned into three groups: without CVVH treatment (sham); standard volume CVVH at a filtration rate of 35-45 mL/kg/h; and high-volume hemofiltration (HVHF, 105-135 mL/kg/h). Hemofiltration was started simultaneously with CPB and maintained for 6 h. Plasma TNFα and IL-6 levels were measured at baseline, 0.5, 1, 2, 3, and 6 h after reperfusion. Survival time, neurological deficit score, and hemodynamic status were assessed. RESULTS: All animals survived over 6 h and died within 24 h. There were no significant differences in survival time (log-rank test, sham vs. CVVH; p = 0.49, sham vs. HVHF; p = 0.33) or neurological deficit scores (ANOVA, p = 0.14) between the groups. There were no significant differences in blood cytokine levels between the groups. Mean blood pressure in sham group animals increased to 1.5-fold higher than baseline levels at 30 min. HVHF significantly reduced blood pressure to 0.7-fold of sham group (p < 0.01). CONCLUSIONS: There was no improvement in mortality, neurological dysfunction, TNFα, or IL-6 levels in rats after prolonged CA with CPB on either hemofiltration group when compared to the sham group.

Accumulating evidence illustrates the beneficial effects of dietary docosahexaenoic acid (DHA) on cardiovascular diseases. However, its effects on cardiac arrest (CA) remain controversial in epidemiological studies and have not been reported in controlled animal studies. Here, we examined whether dietary DHA can improve survival, the most important endpoint in CA. Male Sprague-Dawley rats were randomized into two groups and received either a control diet or a DHA-supplemented diet for 7-8 weeks. Rats were then subjected to 20 min asphyxia-induced cardiac arrest followed by 30 min cardiopulmonary bypass resuscitation. Rat survival was monitored for additional 3.5 h following resuscitation. In the control group, 1 of 9 rats survived for 4 h, whereas 6 of 9 rats survived in the DHA-treated group. Surviving rats in the DHA-treated group displayed moderately improved hemodynamics compared to rats in the control group 1 h after the start of resuscitation. Rats in the control group showed no sign of brain function whereas rats in the DHA-treated group had recurrent seizures and spontaneous respiration, suggesting dietary DHA also protects the brain. Overall, our study shows that dietary DHA significantly improves rat survival following 20 min of severe CA.

Case: A 19-year-old man with a hemangioma that extended from the left arm to the axillary region had deteriorated due to shock, and no improvement was observed after fluid resuscitation. His status on arrival led to complications of hemorrhagic and septic shock with his left arm swollen and deep purple in color. Left arm amputation to control the source of bleeding and infection was thought to be indicated, however, the coagulation system had collapsed. Therefore, initial reduction of the blood flow to the hemangioma with angiographic endovascular treatment was carried out. Thereafter, continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter against hypercytokinemia was introduced in the intensive care unit for damage control, which resulted in success. Outcome: We completed the arm amputation, and subsequently carried out a latissimus dorsi muscle flap transfer on the amputated stump. The patient achieved an ambulatory discharge. Conclusions: We successfully treated the very rare case of massive venous malformation with shock due to hemorrhage and infection by performing damage control.

BACKGROUND: Whether temporal differences alter the clinical outcomes of patients with out-of-hospital cardiac arrest (OHCA) remains inconclusive. Furthermore, the relationship between time of day and resuscitation efforts is unknown. METHODS: We studied adult OHCA patients in the Survey of Survivors after Out-of-Hospital Cardiac Arrest in the Kanto Region (SOS-KANTO) 2012 study from January 2012 to March 2013 in Japan. The primary variable was 1-month survival. The secondary outcome variables were prehospital and in-hospital resuscitation efforts by bystanders, emergency medical services personnel, and in-hospital healthcare providers. Daytime was defined as 0701 to 1500 h, evening was defined as 1501 to 2300 h, and night was defined as 2301 to 0700 h. RESULTS: During the study period, 13,780 patients were included in the analysis. The patients with night OHCA had significantly lower 1-month survival compared to the patients with daytime OHCA (night vs. daytime, adjusted odds ratio (OR) 1.66; 95 % confidence interval (CI), 1.34-2.07; P < 0.0001). The nighttime OHCA patients had significantly shorter call-response intervals, bystander CPR, in-hospital intubation, and in-hospital blood gas analyses compared to the daytime and evening OHCA patients (call-response interval: OR 0.95 and 95 % CI 0.93-0.96; bystander CPR: OR 0.85 and 95 % CI 0.78-0.93; in-hospital intubation: OR 0.85 and 95 % CI 0.74-0.97; and in-hospital blood gas analysis: OR 0.86 and 95 % CI 0.75-0.98). CONCLUSIONS: There was a significant temporal difference in 1-month survival after OHCA. The nighttime OHCA patients had significantly decreased resuscitation efforts by bystanders and in-hospital healthcare providers compared to those with evening and daytime OHCA.

Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

BACKGROUND: Systemic immune response to injury plays a key role in the pathophysiological mechanism of blunt trauma. We tested the hypothesis that increased blood interleukin-6 (IL-6) levels of blunt trauma patients on emergency department (ED) arrival are associated with poor clinical outcomes, and investigated the utility of rapid measurement of the blood IL-6 level. METHODS: We enrolled 208 consecutive trauma patients who were transferred from the scene of an accident to a level I trauma centre in Japan and admitted to the intensive care unit (ICU). Blood IL-6 levels on ED arrival were measured by using a rapid measurement assay. The primary outcome variable was prolonged ICU stay (length of ICU stay > 7 days). The secondary outcomes were 28-day mortality, probability of survival and Abbreviated Injury Scale (AIS) scores. RESULTS: Patients with prolonged ICU stay had significantly higher blood IL-6 levels on ED arrival than the patients without prolonged ICU stay (P < 0.0001). The receiver-operating characteristic curves produced an area under the curve of 0.75 (95 % confidence interval [CI], 0.66-0.84; P < 0.0001) for prolonged ICU stay. The patients who had increased blood IL-6 levels on ED arrival had increased 28-day mortality (P = 0.021) and decreased probability of survival (P < 0.0001). The AIS scores for the thorax, abdomen, extremity, and external body regions independently correlated with blood IL-6 levels (unstandardized coefficients [95 % CI] for the thorax: 23.8 [12.6-35.1]; P < 0.0001; abdomen: 42.7 [23.8-61.7]; P < 0.0001; extremity: 19.0 [5.5-32.4]; P = 0.0060; external body regions: 62.9 [13.2-112.7]; P = 0.030); the standardized coefficients for the thorax (0.27) and abdomen (0.28) were larger than those for the extremity (0.18) and external body regions (0.15). CONCLUSIONS: Increased blood IL-6 level on ED arrival was significantly associated with prolonged length of ICU stay. Blood IL-6 level on ED arrival independently correlated with the AIS scores for the abdomen and thorax, and, to a lesser extent, those for the extremity and external body regions. The rapid measurement of blood IL-6 level on ED arrival can be utilized as a fast screening tool to improve assessment of injury severity and prediction of clinical outcomes in the initial phase of trauma care.

PURPOSE: The medical emergency team (MET) can be activated anytime and anywhere in a hospital. We hypothesized the timing and location of MET activation are associated with seriousness of outcome. MATERIALS AND METHODS: We tested for an association of clinical outcomes with timing and location using a university hospital cohort in Japan (n = 328). The primary outcome was short-term serious outcome (unplanned ICU admission after MET activation or death at scene). RESULTS: Patients for whom the MET was activated in the evening or night-time had significantly higher rates of short-term serious outcome than those for whom it was activated during the daytime (vs. evening: adjusted OR = 2. 53, 95% CI = 1.24-5.13, P = 0.010; night-time: adjusted OR = 2.45, 95% CI = 1.09-5.50, P = 0.030). Patients for whom the MET was activated in public space had decreased short-term serious outcome compared to medical spaces (public space: adjusted OR = 0.19, 95% CI = 0.07-0.54, P = 0.0017). Night-time (vs. daytime) and medical space (vs. public space) were significantly associated with higher risks of unexpected cardiac arrest and 28-day mortality. CONCLUSIONS: Patients for whom the MET was activated in the evening/night-time, or in medical space, had a higher rate of short-term serious outcomes. Taking measures against these risk factors may improve MET performance.

Cardiac arrest (CA) induces whole-body ischemia, causing damage to multiple organs. Ischemic damage to the brain is mainly responsible for patient mortality. However, the molecular mechanism responsible for brain damage is not understood. Prior studies have provided evidence that degradation of membrane phospholipids plays key roles in ischemia/reperfusion injury. The aim of this study is to correlate organ damage to phospholipid alterations following 30 min asphyxia-induced CA or CA followed by cardiopulmonary bypass (CPB) resuscitation using a rat model. Following 30 min CA and CPB resuscitation, rats showed no brain function, moderately compromised heart function, and died within a few hours; typical outcomes of severe CA. However, we did not find any significant change in the content or composition of phospholipids in either tissue following 30 min CA or CA followed by CPB resuscitation. We found a substantial increase in lysophosphatidylinositol in both tissues, and a small increase in lysophosphatidylethanolamine and lysophosphatidylcholine only in brain tissue following CA. CPB resuscitation significantly decreased lysophosphatidylinositol but did not alter the other lyso species. These results indicate that a decrease in phospholipids is not a cause of brain damage in CA or a characteristic of brain ischemia. However, a significant increase in lysophosphatidylcholine and lysophosphatidylethanolamine found only in the brain with more damage suggests that impaired phospholipid metabolism may be correlated with the severity of ischemia in CA. In addition, the unique response of lysophosphatidylinositol suggests that phosphatidylinositol metabolism is highly sensitive to cellular conditions altered by ischemia and resuscitation.

INTRODUCTION: Previous studies evaluating whether subsequent conversion to shockable rhythms in patients who had initially non-shockable rhythms was associated with altered clinical outcome reported inconsistent results. Therefore, we hypothesized that subsequent shock delivery by emergency medical service (EMS) providers altered clinical outcomes in patients with initially non-shockable rhythms. METHODS: We tested for an association between subsequent shock delivery in EMS resuscitation and clinical outcomes in patients with initially non-shockable rhythms (n = 11,481) through a survey of patients after out-of-hospital cardiac arrest in the Kanto region (SOS-KANTO) 2012 study cohort, Japan. The primary investigated outcome was 1-month survival with favorable neurological functions. The secondary outcome variable was the presence of subsequent shock delivery. We further evaluated the association of interval from initiation of cardiopulmonary resuscitation to shock with clinical outcomes. RESULTS: In the univariate analysis of initially non-shockable rhythms, patients who received subsequent shock delivery had significantly increased frequency of return of spontaneous circulation, 24-hour survival, 1-month survival, and favorable neurological outcomes compared to the subsequent not shocked group (P < 0.0001). In the multivariate logistic regression analysis, subsequent shock was significantly associated with favorable neurological outcomes (vs. not shocked; adjusted P = 0.0020, odds ratio, 2.78; 95% confidence interval, 1.45-5.30). Younger age, witnessed arrest, initial pulseless electrical activity rhythms, and cardiac etiology were significantly associated with the presence of subsequent shock in patients with initially non-shockable rhythms. CONCLUSIONS: In this study of cardiac arrest patients with initially non-shockable rhythms, patients who received early defibrillation by EMS providers had increased 1-month favorable neurological outcomes.

BACKGROUND: Emerging therapies for prolonged cardiac arrest (CA) include advanced circulatory interventions like emergency cardiopulmonary bypass (ECPB) and continuous venovenous hemofiltration (CVVHF). However, preclinical studies are limited because of the absence of a practical method of using CVVHF along with ECPB in rodents. METHODS: We modified a CA model with ECPB resuscitation to include the CVVHF circuit. Adult rats were cannulated via the femoral artery or vein and the jugular vein for the ECPB circuit. A new circuit for CVVHF was added to allow ECPB and CVVHF to be started simultaneously. CVVHF blood flow at 3 mL/min could be controlled with a screw clamp during ECPB. After cessation of ECPB, the CVVHF flow was maintained using a roller pump. The filtration rate was controlled at 40 mL/h/kg in the standard volume of CVVHF and 120 mL/h/kg in the high volume (HV) of CVVHF. The driving force of hemofiltration was evaluated by monitoring transmembrane pressure and filter clearance (FCL). RESULTS: Transmembrane pressure in both groups was stable for 6 h throughout CVVHF. FCL of blood urea nitrogen and potassium in the standard volume group was significantly less than the HV group (P < 0.01). FCL of blood urea nitrogen and potassium was stable throughout the CVVHF operation in both groups. CONCLUSIONS: We developed a method of CVVHF along with ECPB in rodents after CA. We further demonstrated the ability to regulate both standard and HV filtration rates.

OBJECTIVE: Autophagy is the regulated catabolic process for recycling damaged or unnecessary organelles, which plays crucial roles in cell survival during nutrient deficiency, and innate immune defense against pathogenic microorganisms. Autophagy has been also reported to be involved in various conditions including inflammatory diseases. IRGM (human immunity-related GTPase) has an important function in eliminating Mycobacterium tuberculosis from host cells via autophagy. We examined the association between genetic polymorphism and clinical course/outcome in severely septic patients. METHODS: The study included 125 patients with severe sepsis/septic shock (SS) and 104 non-sepsis patients who were admitted to the intensive care unit (ICU) of Chiba University Hospital between October 2001 and September 2008 (discovery cohort) and 268 SS patients and 454 non-sepsis patients who were admitted to ICUs of five Japanese institutions including Chiba University Hospital between October 2008 and September 2012 (multi-center validation cohort). Three hundred forty seven healthy volunteers who consented to this study were also included. Genotyping was performed for a single-nucleotide polymorphism (SNP) within the coding region of IRGM, IRGM(+313) (rs10065172). Lipopolysaccharide challenge of whole blood from randomly selected healthy volunteers (n = 70) was performed for comparison of IRGM mRNA expression among different genotypes. RESULTS: No significant difference in genotypic distributions (CC/CT/TT) at the IRGM(+313) locus was observed among the three subject groups (SS, non-sepsis, and healthy volunteers) in either cohort. When mortality were compared, no significant difference was observed in the non-sepsis group, while TT homozygotes exhibited a significantly higher mortality than the CC+CT genotype category in the SS group for both cohorts (P = 0.043, 0.037). Lipopolysaccharide challenge to whole blood showed a significant suppression of IRGM mRNA expression in TT compared with the CC+CT genotype category (P = 0.019). CONCLUSIONS: The data suggest that the IRGM(+313), an autophagy-related polymorphic locus, influences outcome in severely septic patients, with the possible involvement of autophagy in sepsis exacerbation.

BACKGROUND: Cardiac arrest induces whole body ischemia, which causes damage to multiple organs particularly the heart and the brain. There is clinical and preclinical evidence that neurological injury is responsible for high mortality and morbidity of patients even after successful cardiopulmonary resuscitation. A better understanding of the metabolic alterations in the brain during ischemia will enable the development of better targeted resuscitation protocols that repair the ischemic damage and minimize the additional damage caused by reperfusion. METHOD: A validated whole body model of rodent arrest followed by resuscitation was utilized; animals were randomized into three groups: control, 30 minute asphyxial arrest, or 30 minutes asphyxial arrest followed by 60 min cardiopulmonary bypass (CPB) resuscitation. Blood gases and hemodynamics were monitored during the procedures. An untargeted metabolic survey of heart and brain tissues following cardiac arrest and after CPB resuscitation was conducted to better define the alterations associated with each condition. RESULTS: After 30 min cardiac arrest and 60 min CPB, the rats exhibited no observable brain function and weakened heart function in a physiological assessment. Heart and brain tissues harvested following 30 min ischemia had significant changes in the concentration of metabolites in lipid and carbohydrate metabolism. In addition, the brain had increased lysophospholipid content. CPB resuscitation significantly normalized metabolite concentrations in the heart tissue, but not in the brain tissue. CONCLUSION: The observation that metabolic alterations are seen primarily during cardiac arrest suggests that the events of ischemia are the major cause of neurological damage in our rat model of asphyxia-CPB resuscitation. Impaired glycolysis and increased lysophospholipids observed only in the brain suggest that altered energy metabolism and phospholipid degradation may be a central mechanism in unresuscitatable brain damage.

PURPOSE: Detailed procedures for optimal therapeutic hypothermia (TH) have yet to be established. We examined how duration of well-controlled core temperature within the first 24 hours after cardiac arrests (CA) correlated with neurological outcomes of successfully resuscitated out-of-hospital CA (OHCA) patients. METHODS: OHCA patients who survived over 24 hours and treated with TH were included. Core temperature was measured every hour. Physicians intended to maintain temperature at 33 °C ± 1 °C for 24 hours. Cerebral performance categories (CPC) of patients at 6 months were recorded and patients were retrospectively divided into favorable (CPC1,2) and poor (CPC3-5) neurological outcome groups. Total time while the core temperature reached to 33 °C ± 1 °C within the first 24 hours after CA was measured and this duration was defined that of well-controlled temperature. receiver-operating characteristic analysis was performed on duration of well-controlled temperature to select the optimal cutoff value. Neurological outcome predictors were investigated by logistic regression analysis. RESULTS: Fifty-six patients were included. Optimal cutoff value of duration of well-controlled temperature was 18 hours. Ratio of male sex, witnessed by emergency medical service (EMS) personnel, first electrocardiogram as shockable, and duration of well-controlled core temperature ≥ 18 h of favorable neurological outcome group (n = 21) were significantly larger than that of poor neurological outcome group (n = 35). Logistic regression analysis identified "witnessed by EMS", "performed bystander CPR," and "the duration ≥ 18 h" as independent predictors of favorable neurological outcome. CONCLUSION: TH maintained at target temperature of 33 °C ± 1 °C over 18 hours independently correlated with favorable neurological outcome. Therefore, stable core temperature control may improve neurological outcome of successfully resuscitated OHCA.

重症急性膵炎における早期経腸栄養は、感染症発症率や死亡率の低下をもたらすことから第一選択の栄養管理法として推奨されているが、本邦での施行率は低い。本研究は重症急性膵炎の栄養管理について多施設で現状を前向きに調査・解析し、その課題を明らかにすることを目的とした。2009年1月から2011年3月までに早期経腸栄養を行うプロトコールに則り、8施設から計43例(男性32例、女性11例)が本研究に組み入れられた。平均年齢は56.5±2.4歳で、発症から入院までは平均1.4±0.2日であった。入院時の予後因子は4.0±0.2、APACHE IIスコアは13.7±1.3であった。事前に設定された経腸栄養開始基準に準じて経腸栄養が施行された症例は30例(69.8%)で、48時間以内開始は4例(9.3%)であった。開始時期の中央値は5.5日であった。経腸栄養開始遅延の理由は膵酵素高値が最多であった。イレウス症状(22%)と循環不全(12%)を含む51%は早期経腸栄養開始が困難と考えられる症例であった。経腸栄養中止に至った症例は3例で(10%)、理由は重症下痢、偽膜性腸炎、イレウス症状が1例ずつであった。中止例の入院期間はそれ以外の症例に比し延長していた(p=0.02)。48時間以内早期経腸栄養群(n=4)と7日以内に経腸栄養が開始されなかった群(n=22)の、入院7日目までの血清アミラーゼ値は絶対値(p>0.05)、その経時推移(p=0.64)ともに群間に有意差を認めず、両群で概ね順調な低下傾向を認めた。C-reactive proteinについても群間差を認めなかった(p>0.05、p=0.97)。48時間以内早期経腸栄養群、7日以内に経腸栄養が開始された群、7日以内に経腸栄養が開始されなかった群の、手術移行の有無、感染性合併症の有無、ICU滞在日数、入院日数に群間差を認めなかった。重症急性膵炎症例の約半数で早期経腸栄養開始に慎重な判断が必要である可能性が示唆された。(著者抄録)

Various approaches such as ventilator management involving lung-protective ventilation, corticosteroids, prone positioning, and nitric oxide have failed to maintain sufficient lung oxygenation or appropriate ventilation competence in very severe acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) has been aggressively introduced for such patients, although in only a few institutions. The clinical usefulness of ECMO in a large-scale multicenter study (CESAR trial, 2009) and continued development/improvement of ECMO devices have facilitated performance of ECMO, with further increase in the number of institutions adopting ECMO therapy. Clinical usefulness of ECMO was documented in many cases of severe ARDS secondary to influenza A (H1N1) 2009 infection. ECMO requires establishment of an appropriate management system to minimize fatal complications (e.g., hemorrhage), which requires a multidisciplinary team. This, in combination with a new technique, interventional lung assist, will further extend the indications for ECMO. ECMO can be expected to gain importance as a respiratory support technique.

近年、心肺停止(CPA:cardiopulmonary arrest)症例に対するCPR(cardiopulmonary resuscitation)の進歩はめざましい。しかしながら、救急医療における進歩の傍ら常に考えなければならない問題が、救急医療領域でのmedical futilityである。本稿ではCPRに付随したmedical futilityを回避するための予後予測因子に関して解説する。また、当施設におけるアンモニアと乳酸血中濃度の神経学的予後予測因子としての有用性に関する検討の結果を示す。(著者抄録)

PURPOSE: Cytokines play pivotal roles in the pathophysiology of severe sepsis/septic shock, and continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF) removes cytokines efficiently and continuously, mainly through adsorption to a hemofilter membrane. The aim of this study was to investigate the clinical efficacy of enhanced intensity PMMA-CHDF in treating refractory septic shock. METHODS: Seventy-two septic shock patients admitted to the intensive care unit (ICU) underwent critical care including PMMA-CHDF. We employed enhanced intensity PMMA-CHDF to improve the cytokine removal rate by increasing the hemofilter membrane area in 10 refractory septic shock patients (enhanced intensity group, EI group; 2 extracorporeal CHDF circuits using the hemofilter with a larger membrane area of 2.1 m2). Other patients undergoing conventional PMMA-CHDF and matched for severity with the EI group, comprised a matched conventional group (MC group; using a PMMA membrane hemofilter with a membrane area of 1.0 m2; n=15). The case-control comparison was performed between the 2 groups. RESULTS: Enhanced intensity PMMA-CHDF significantly increased mean arterial pressure by 23.8% in 1 hour (p=0.037), decreased the blood lactate level by 28.6% in 12 hours (p=0.006), and reduced blood IL-6 level in 24 hours (p=0.005). The ICU survival rate in the EI group was significantly better than that in the MC group (60% vs. 13.3%, p=0.028). CONCLUSION: Enhanced intensity PMMA-CHDF may improve hemodynamics and survival rate in patients with refractory septic shock.

In general, a prediction of neurologic outcome with respect to the resuscitated cardiac arrest patients has been performed by the auditory brainstem response and somatic evoked potential. The auditory brainstem response and somatic evoked potential are known as the predictors that correspond to neurologically poor outcome. None of the methods have been established to access neurologically good outcome. Because the hippocampal CA3 pyramidal cells have been widely used for pathophysiologic analyses concerning the hypoxic-ischemic encephalopathy and also the source of P50 components of the auditory evoked potential has been considered to be the hippocampal CA3 pyramidal cells, the authors assume that it might be possible that neurologic outcome in resuscitated cardiac arrest patients would be predicted by evaluating the P50 components. The purpose was to examine the P50 as a predictor of neurologic outcome in resuscitated cardiac arrest patients at the early stage from the onset. The P50 components of the auditory evoked potential are recorded in a conditioning-testing paradigm, that is, EEG responses to a pair of auditory stimuli with 500-millisecond interclick interval. In this study, subjects are 10 out-of-hospital cardiac arrest patients, 8 men and 2 women with a mean age of 54.8 years, who were admitted to the intensive care unit after the return of spontaneous circulation, with the presence of both the auditory brainstem response wave V and the somatic evoked potential wave N20 between the period from June 2008 to July 2009. It was found that the presence of the P50 at the early stage from the onset (days 5 ± 1.20) indicates good neurologic outcome, while the absence of the P50 implies poor prognosis. As to the auditory sensory gating of the P50, almost no reduction response to the second stimulus was observed. As a consequence, the evaluation of the P50 in resuscitated cardiac arrest patients would have a possibility to predict neurologically good outcome.

INTRODUCTION: No reliable predictor for the prognosis of out-of-hospital cardiac arrest (OHCA) on arrival at hospital has been identified so far. We speculate that ammonia and lactate may predict patient outcome. METHODS: This is a prospective observational study. Non-traumatic OHCA patients who gained sustained return of spontaneous circulation and were admitted to acute care unit were included. Blood ammonia and lactate levels were measured on arrival at hospital. The patients were classified into two groups: 'favourable outcome' group (Cerebral Performance Category CPC1-2 at 6-months' follow-up) and 'poor outcome' group (CPC3-5). Basal characteristics obtained from the Utstein template and biomarker levels were compared between these two outcome groups. Independent predictors were selected from all candidates using logistic regression analysis. RESULTS: A total of 98 patients were included. Ammonia and lactate levels in the favourable outcome group (n=10) were significantly lower than those in poor outcome group (n=88) (p<0.05, respectively). On receiver operating characteristic analysis, the optimal cut-off value for predicting favourable outcome was determined as 170 μg dl(-1) of ammonia and 12.0 mmol l(-1) of lactate (area under the curve; 0.714 and 0.735, respectively). Logistic regression analysis identified ammonia (≤170 μg dl(-1)), therapeutic hypothermia and witnessed by emergency medical service personnel as independent predictors of favourable outcome. When both these biomarker levels were over threshold, positive predictive value (PPV) for poor outcome was calculated as 100%. CONCLUSIONS: Blood ammonia and lactate levels on arrival are independent prognostic factors for OHCA. PPV with the combination of these biomarkers predicting poor outcome is high enough to be useful in clinical settings.

Extracorporeal membrane oxygenation(ECMO)の適応症例は、循環不全を伴わない呼吸不全症例であり、従来の呼吸補助療法では救命困難と判断される。重篤な呼吸不全を呈する症例である。重篤且つ遭遇頻度の高い病態であるARDS(acute respiratory distress syndrome)の治療戦略の中心は肺保護戦略(lung protective ventilation strategy)に基づいた人工呼吸管理である。低1回換気量、低気道内圧を主眼においたlung protective ventilationを実践したうえで、ガス交換能を適正に保つことがECMO施行の目的である。本稿ではECMOの有効性に関する最新の知見を紹介するとともに、当部で施行しているECMOの具体的施行法を解説する。(著者抄録)

CRRTとは,「持続的腎機能代替療法」である.本来は「腎補助を目的とする場合にのみ使用し,non-renal indicationは含まない」用語である.しかしながら,医工学の進歩により,現在さまざまな血液浄化法が開発され,臨床応用されているなかで,CRRTの正確な位置づけをすることは難しい.本稿ではCRRTに関する理解を助ける目的で,現在本邦で行われている血液浄化法の種類を概説し,そのうえで欧米諸国の報告を含めた最新の知見をもとにCRRTについて解説し,CRRTの具体的な施行法や適応について講述する.(著者抄録)

高度かつ高額な医療が進歩し、生存率が急激に向上する傍らに問題となるのが、medical futilityである。本稿では心停止後脳傷害(PCABI)に付随したmedical futilityを回避するためのprognostic biomarkerの中で、Neuron Specific Enolase(NSE)とS100Bを取り上げて解説した。予後予測においてNSE測定が欧米で推奨されつつあるものの、偽陽性の問題からNSE単独で評価せず、画像や電気生理検査を組み合わせるべきとの見方が一般的である。一方で、PCABIの病態生理が脚光をあびている。そのため、biomarkerのなかでもprognostic biomarkerとしての役割のみでなく、病態に関わるmediatorとしての役割を有すると考えられるS100Bは、研究価値が高く、臨床応用すべきbiomarkerになりえるとわれわれは考える。(著者抄録)

2008年、『Critical Care Medicine』に掲載されたSurviving Sepsis Campaign Guidelinesはsepsisに起因するARDSに対して、Supportive therapyとしての人工呼吸器を用いた治療戦略を具体的に示した。そのなかで、とくにlow tidal volumeによる肺保護戦略(lung protective strategy)が肝要とされている。しかし、最重症型のARDSをlung protective strategyのみで救命することはいまだに難しい。著者らはPaO2/FIO2比100mmHg以下の重症ARDSに対して原疾患が可逆的であると判断した場合に、lung protective strategyに加えてECMO(extracorporeal membrane oxygenation)を併用した治療戦略を実践してきた。本稿ではARDSに対するECMOに関して、当部におけるECMOの具体的施行方法を示し、新旧含めた海外での知見を紹介するとともに、実際に当部で経験したECMO施行例について示す。(著者抄録)

神経性食思不振症(anorexia nervosa、AN)は時に致死的となりうる病態であり、その集中治療には特別な配慮が必要である。今回、敗血症の治療経過中に、低リン血症を呈したANの2例を経験した。症例は55歳女性と31歳女性で、両者とも自宅にて意識レベルが低下し、当院に搬送された。来院時ショック状態であり、低血糖補正後も意識レベルの改善がなく、ICUに入室した。両者とも敗血症を呈していたにもかかわらず、血中interleukin-6濃度は高値を示さなかった。また、来院時は高リン血症を示すも、栄養開始後に血清リン値は激減し、体内のリン不足が明らかとなった。経過は良好で、第5病日に一般病棟へ転棟した。ANでは、炎症に対する生体反応の低下が推測され、注意を要する。また、体内のリン不足が必ずしも血清リン値に反映されるとは限らないため、AN患者の栄養管理には投与エネルギーの制限、連日の血清リン値測定、および的確なリンの補充が重要であると考えられた。(著者抄録)

INTRODUCTION: Bacteremia is recognized as a critical condition that influences the outcome of sepsis. Although large-scale surveillance studies of bacterial species causing bacteremia have been published, the pathophysiological differences in bacteremias with different causative bacterial species remain unclear. The objective of the present study is to investigate the differences in pathophysiology and the clinical course of bacteremia caused by different bacterial species. METHODS: We reviewed the medical records of all consecutive patients admitted to the general intensive care unit (ICU) of a university teaching hospital during the eight-year period since introduction of a rapid assay for interleukin (IL)-6 blood level to routine ICU practice in May 2000. White blood cell count, C-reactive protein (CRP), IL-6 blood level, and clinical course were compared among different pathogenic bacterial species. RESULTS: The 259 eligible patients, as well as 515 eligible culture-positive blood samples collected from them, were included in this study. CRP, IL-6 blood level, and mortality were significantly higher in the septic shock group (n = 57) than in the sepsis group (n = 127) (P < 0.001). The 515 eligible culture-positive blood samples harbored a total of 593 isolates of microorganisms (Gram-positive, 407; Gram-negative, 176; fungi, 10). The incidence of Gram-negative bacteremia was significantly higher in the septic shock group than in the sepsis group (P < 0.001) and in the severe sepsis group (n = 75, P < 0.01). CRP and IL-6 blood level were significantly higher in Gram-negative bacteremia (n = 176) than in Gram-positive bacteremia (n = 407) (P < 0.001, <0.0005, respectively). CONCLUSIONS: The incidence of Gram-negative bacteremia was significantly higher in bacteremic ICU patients with septic shock than in those with sepsis or severe sepsis. Furthermore, CRP and IL-6 levels were significantly higher in Gram-negative bacteremia than in Gram-positive bacteremia. These findings suggest that differences in host responses and virulence mechanisms of different pathogenic microorganisms should be considered in treatment of bacteremic patients, and that new countermeasures beyond conventional antimicrobial medications are urgently needed.

It has been reported that hypercytokinemia plays a pivotal role in the pathophysiology of severe acute pancreatitis (SAP). In our previous reports, continuous hemodiafiltration (CHDF) using a polymethyl methacrylate (PMMA) membrane hemofilter (PMMA-CHDF) was found to be capable of efficiently removing various cytokines from circulating blood. The present study was undertaken to evaluate the efficacy of PMMA-CHDF aimed at cytokine removal in the treatment of SAP. Patients with blood IL-6 level > or =400 pg/ml were considered indicated for initiation of PMMA-CHDF based on our previous data. Among the patients enrolled in the present study, there were significant differences in APACHE II sore, JMHLW (Japanese Ministry of Health, Labour, and Welfare) severity score, Ranson score, blood lactate level on ICU admission, and length of ICU stay between patients with blood IL-6 levels > or =400 pg/ml and patients with levels < 400 pg/ml. Using this PMMA-CHDF initiation criterion, PMMA-CHDF was performed on 82 SAP patients. Mean blood IL-6 level, which was 998 pg/ml on admission to the ICU, was significantly lower (335 pg/ml) after 3 days treatment of PMMA-CHDF (p < 0.01). In addition, heart rate, blood lactate level, and intra-abdominal pressure also decreased significantly (p < 0.01). At the time of weaning from PMMA-CHDF, blood IL-6 level had decreased to 99 pg/ml. The mortality rate among patients who received PMMA-CHDF was 6.1%, and significantly lower than that of patients before the introduction of PMMA-CHDF under non-renal indication (25.0%). These findings suggest that PMMA-CHDF is effective for treatment of SAP and that it can be expected to contribute to improving the outcome of SAP patients.

Fulminant hepatic failure (FHF) can be described as a potentially fatal condition presenting with hepatic encephalopathy (HE) and coagulopathy associated with acute hepatic dysfunction, regardless of its etiology. Blood purification (BP) is expected to be effective against HE and coagulopathy in FHF. In this paper, we outline the objectives and methods of BP in the treatments of cases with FHF and indicate a concrete method for and outcomes of BP at our facility. In high-flow dialysate continuous hemodiafiltration (HFCHDF), the conventional CHDF bedside console is connected to a personal dialysis console to induce a high flow rate of dialysate. With this method, the dialysate flow rate is about 500 ml/min at maximum, equivalent to about 50 times the dialysate flow rate during ordinary CHDF. The role of plasma exchange (PE) is considered a means of replacing useful substances, such as clotting factors in fresh frozen plasma rather than a means of removing pathogenic substances. As needed, slow PE (SPE) can be incorporated by connection in series. Analysis of data from 90 patients with FHF who underwent BP at our facility after 1990 revealed that restoration of consciousness was achieved in 33 (70.2%) of 47 cases when treated with HFCHDF. This survival in the HFCHDF group was significantly higher than that in the CHDF group. Analysis of data from cases in which ammonia could be measured continuously revealed that blood ammonia level decreased over time following HFCHDF. We also revealed that HFCHDF was useful for preventing the side effects of PE, such as hypernatremia, metabolic alkalosis, and sharp decrease in colloid osmotic pressure. It is concluded that HFCHDF is useful in the treatment of HE and for preventing the side effects of PE. Therefore, we suggested that HFCHDF + SPE should be standardized for the treatment of FHF.

Severe sepsis/septic shockに対するearly goal-directed therapy(EGDT)は組織酸素代謝失調(dysoxia)の早期改善を視野に入れた循環管理法で、有用性の高い治療法の一つである。しかしながらRiversらの検討以来、追跡検討はなされておらず、幾つかの問題点も存在する。我々はEGDTの問題点として、(1)SvO2やScvO2はdysoxiaの指標として限界がある事、(2)dysoxia対策にはhypercytokinemia対策も必要である事、等を取り上げてきた。これらを鑑み、我々は血中乳酸値をdysoxiaの指標とし、高乳酸血症の早期改善を目指したEGDTと、cytokine除去能に優れたPMMA膜hemofilterを用いたCHDF(PMMA-CHDF)を併せてseptic shock発症早期から施行しており、良好な治療成績を得ている。以上よりsevere sepsis/septic shockにおけるdysoxia対策には高乳酸血症改善を目標としたEGDTとPMMA-CHDFによるhypercytokinemia対策を併せて実施する事が必要であると考えられた。(著者抄録)

To investigate changes in protein expression by proteomic analysis in the sera of patients with sepsis and to identify new biomarkers of sepsis. A total of 45 consecutive patients with severe sepsis or septic shock (sepsis group), 22 healthy volunteers, and 23 patients undergoing off-pump coronary artery bypass grafting (control group). Serum samples from eight patients of each group underwent proteomic analysis involving removal of 12 major proteins and subsequent reversed-phase high-performance liquid chromatography fractionation and one-dimensional electrophoresis. The intensity of 41 bands (with 12 proteins identified) increased and that of 42 bands (with 22 proteins identified) decreased in the sepsis group. Results of proteomic analysis successfully validated by Western blotting and/or enzyme-linked immunosorbent assay for three proteins (YKL-40, lipocalin 2, and S100A9) increased in the sepsis group as well as two proteins (retinol-binding protein, vitamin D-binding protein) decreased. Serum YKL-40 levels (sYKL-40) on intensive care unit (ICU) admission were assessed by enzyme-linked immunosorbent assay between the two groups; resulting YKL-40 was significantly higher in the sepsis group (P < 0.001). Furthermore, sYKL-40 on ICU admission was significantly higher in patients with positive blood culture (P < 0.005), patients with septic shock (P < 0.05), and patients requiring continuous hemodiafiltration (P < 0.05) or hydrocortisone replacement therapy (P < 0.005) during subsequent treatment. A positive correlation between sYKL-40 and blood IL-6 level on ICU admission was noted in the sepsis group (r = 0.465, P < 0.01). YKL-40 identified by proteomic analysis is considered as a biomarker of sepsis. However, further investigation is needed to clarify its roles and clinical usefulness as a biomarker.

近年、心肺停止(CPA:cardiopulmonary arrest)症例に対するCPR(cardiopulmonary resuscitation)の進歩はめざましい。しかしながら、救急医療における進歩の傍ら常に考えなければならない問題が、救急医療領域でのmedical futilityである。本稿ではCPRに付随したmedical futilityを回避するための予後予測因子に関して解説する。また、当部において前向き観察研究を施行中である。NSE、S-100Bの神経学的予後予測因子としての有用性に関して報告するとともに、当部での神経学的予後予測因子を用いたCPR後medical futilityの回避の現状について解説する。(著者抄録)

INTRODUCTION: Most patients with cardiac arrest (CA) admitted to hospitals after successful cardiopulmonary resuscitation (CPR) are discharged with various degree of neurological deficits. To determine predictor of neurological outcome early and accurately, and to determine cutoff values, serum levels of protein S-100B and neuron-specific enolase (NSE) within 24h after CA were assessed. METHODS AND RESULTS: A multicenter prospective observational study was conducted between May 2007 and April 2008 at three medical institutions in Japan on 107 consecutive non-traumatic CA patients with return of spontaneous circulation after CPR. Based on "best-ever achieved" Glasgow-Pittsburgh cerebral performance categories (CPC) score within 6 months after CA, patients were classified into a "poor neurological outcome" group (CPC3 to CPC5) (n=67) and "favorable neurological outcome" group (CPC1 and CPC2) (n=13). Blood was sampled on admission, at 6 and 24h after CA. Serum S-100B and NSE in "poor outcome" group were higher than those in "favorable outcome" group (P<0.01). On ROC analysis, area under the curve of S-100B was 0.85, 0.94 and 1.0, respectively. These were greater than those of NSE at all sampling points. The "100%-specific" cutoff values of S-100B predictive of poor neurological outcome were 1.41, 0.21, and 0.05ng/mL, respectively. These values corresponded to sensitivities of 20.9%, 62.8%, and 100%, respectively, each of which was higher than those of NSE. CONCLUSIONS: S-100B is more reliable as an early predictor of poor neurological outcome within 24h after CA than NSE and can be applied clinically.

重症急性膵炎は厚生労働省難病対策事業の1つに取り上げられており,その対策が講じられてきた.わが国では2003年に厚生労働省の研究班と関連学会が合同でガイドラインを作成し,2007年に改訂第2版を出版している.このガイドラインでは厚生労働省の急性膵炎の重症度判定基準に従って急性膵炎の重症度判定を行うことを推奨している.このように,わが国では独自のガイドラインに則った重症化予測因子を用いている.本稿では,欧米諸国で主に用いられているRanson score,Glasgow score,acute physiology and chronic health evaluation(APACHE)II scoreの有用性および今後の展望について解説し,また今後注目されると予想される新たな予後予測因子に関して紹介する.(著者抄録)

INTRODUCTION: Neurological prognostic factors after cardiopulmonary resuscitation (CPR) in patients with cardiac arrest (CA) as early and accurately as possible are urgently needed to determine therapeutic strategies after successful CPR. In particular, serum levels of protein neuron-specific enolase (NSE) and S-100B are considered promising candidates for neurological predictors, and many investigations on the clinical usefulness of these markers have been published. However, the design adopted varied from study to study, making a systematic literature review extremely difficult. The present review focuses on the following three respects for the study design: definitions of outcome, value of specificity and time points of blood sampling. METHODS: A Medline search of literature published before August 2008 was performed using the following search terms: "NSE vs CA or CPR", "S100 vs CA or CPR". Publications examining the clinical usefulness of NSE or S-100B as a prognostic predictor in two outcome groups were reviewed. All publications met with inclusion criteria were classified into three groups with respect to the definitions of outcome; "dead or alive", "regained consciousness or remained comatose", and "return to independent daily life or not". The significance of differences between two outcome groups, cutoff values and predictive accuracy on each time points of blood sampling were investigated. RESULTS: A total of 54 papers were retrieved by the initial text search, and 24 were finally selected. In the three classified groups, most of the studies showed the significance of differences and concluded these biomarkers were useful for neurological predictor. However, in view of blood sampling points, the significance was not always detected. Nevertheless, only five studies involved uniform application of a blood sampling schedule with sampling intervals specified based on a set starting point. Specificity was not always set to 100%, therefore it is difficult to indiscriminately assess the cut-off values and its predictive accuracy of these biomarkers in this meta analysis. CONCLUSIONS: In such circumstances, the findings of the present study should aid future investigators in examining the clinical usefulness of these markers and determination of cut-off values.

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease of the central nervous system associated with significant morbidity and mortality. High-dose corticosteroid administration has been considered the mainstay of treatment for ADEM; however, some patients with ADEM are refractory to steroid therapy. We report a case of a 17-year-old man suffering from ADEM who did not respond to corticosteroid therapy, but who exhibited a dramatic recovery with plasmapheresis. He became comatose, requiring ventilatory support, and exhibited abnormalities of some brainstem reflexes prior to treatment. He underwent sequential courses of plasma exchange therapy for three days. Plasma exchanges were carried out with concomitant continuous hemodiafiltration (CHDF) to control intracranial pressure by stabilizing pH, plasma Na+ concentration, and colloid osmotic pressure. After plasma exchanges, his reflexes and level of consciousness gradually improved. Eleven months after this treatment, he had only minimal neurological deficit that did not interfere with any of his activities of daily living. The efficacy of plasmapheresis for ADEM has not yet been established. Plasmapheresis may be indicated for ADEM, not only for patients with severe disease in whom high-dose corticosteroid treatment has failed, but also as first-line treatment for ADEM. Early initiation of plasmapheresis appears to be associated with moderate to marked improvement. Early recognition and early treatment of ADEM are thus of paramount importance.

持続的血液濾過透析(CHDF)を施行した体重5kg以下の新生児19例・乳児2例を、小児用flexible double lumen catheter(FDLC)導入以前の8例(男5例・女3例・平均日齢8.6日:A群)と導入後の13例(男7例・女6例・平均日齢18.2日:B群)に分け、CHDFの成績を比較した。患者背景では性別、日齢、体重、不全臓器数に有意差はなく、重症度スコアはB群が高い傾向であった。CHDF導入直前の時間尿量に有意差はなかったが、血中クレアチニン(Cre)はB群が有意に低値であった。CHDF施行後の体重当たりの平均血流量は、A群2.92mL/min/kg、B群8.50mL/min/kgと有意差を認め、filter lifeもA群平均12.3時間、B群32.4時間と有意に延長していた。またCHDFを3日間施行した後の血中CreもB群で有意に低値で、救命率はA群12.5%、B群61.5%と有意差を認めた。乳児・新生児の血液浄化法におけるバスキュラーアクセスとして、FDLCは有用であることが示された。

重症急性膵炎は、膵局所の炎症によって引き起こされた全身性炎症反応症候群(SIRS)が重症化して臓器障害を発症した状態であり、感染によらないSIRSの典型的な病態と考えられている。このSIRSの本態である高サイトカイン血症を制御するため、PMMA-CHDFは重症急性膵炎に有用であることを、われわれは報告してきた。今回、SAPに続発する多臓器不全の病態生理を概説するとともに、当科におけるPMMA-CHDFの開始のタイミング及びその施行の実際と効果について解説する。この内容を受けて、より多くの症例に、適切なタイミングでPMMA-CHDFが導入され、重症急性膵炎の救命率の向上につながるものと期待している。(著者抄録)

血液浄化法施行例を、開始時出血が持続していた24例(A群)、出血はなかったが検査所見で出血傾向を認めた52例(B群)、出血傾向もなかった126例(C群)、に分け経過を比較した。血液浄化開始後に出血を認めたのはB群12例、C群16例で、出現率に有意差はなかった。A群において、抗凝固剤非使用が11例、通常量より減量使用が10例あり、非使用例のうち2例はhemofilterのlife timeが極端に短縮したため、フサンを少量で開始した。それでも頻回に回路交換となった症例では、カラムの膜素材をPMMAからセルローストリアセテートに変更することで施行時間を延長できた。B群とC群の比較では、救命率がそれぞれ69.2%、82.5%、開始時フサン量が11.3mg/hr、15.8mg/hrと有意差を認め、hemofilterのlife timeには有意差はなかった。両群を出血出現の有無で分け比較したところ、救命率以外に差はみられなかった。全例の血液浄化開始時の平均目標活性化凝固時間(ACT)と出血例の出血直前ACT値の比較では、差はなかった。出血後の対応は、抗凝固剤中止6例、減量13例、経過観察のみ8例、目的達成による血液浄化終了1例で、出血コントロール不良による中止はなかった。

近年、敗血症性ショックに対する循環管理法は凄まじい勢いで進歩しており、その治療成績も向上していると考えられる。しかしながら、敗血症性ショック症例の中には、通常の循環管理に反応せず、急激な経過をとり死亡する場合も存在する。このように激烈な経過をとる敗血症性ショックでは経皮的心肺補助(PCPS)による循環のサポートが必要と考えられるが、敗血症性ショックに対するPCPS治療は侵襲が大きく、一般的ではない。われわれはIABPやCHDFを併用することで、PCPS施行に伴う侵襲を最小限度とするよう配慮し、敗血症性ショックに対しても、適応があればPCPSを施行することにしている。幾つかの工夫を施せば敗血症性ショックにおいてもPCPS治療は、安全にかつ効果的に施行できるものと考えられる。(著者抄録)

持続的血液濾過透析(CHDF)は、SAPに対して広く施行されるようになっている。しかし、SAPの本態である高サイトカイン血症を制御する目的でCHDFを施行する際には、PMMA膜ヘモフィルタを用いたCHDF(PMMA-CHDF)を施行すべきである。PMMA-CHDFは、単なる水分・電解質管理や腎補助としてのみでなく、血中のサイトカインを効率よく除去することにより臓器不全発症を予防するとともに、初期大量輸液によって起こりうる腹部コンパートメント症候群(ACS)の発症予防にも有用である。(著者抄録)

心肺停止症例は心肺蘇生により自己心拍が再開したとしても、蘇生後脳症をはじめとしたさまざまな病態変化をきたし、結果的に救命できないことが多い。近年、これらの自己心拍再開後の病態にhypercytokinemiaを主体とした各種高mediator血症が関与しているといわれており、sepsisの病態に類似していることから、sepsis-like syndromeとして注目されている。今回、心肺蘇生後のsepsis-like syndromeにCHDFが奏功し社会復帰した1例を経験したので報告すると共に、心肺蘇生後のpost-resuscitation careにおけるCHDFの適用の可能性を示した。(著者抄録)

喘息発作は呼吸器系の救急疾患としてよく遭遇する疾患であり、時として集中治療を必要とするような重症喘息発作患者も散見される。そこで、当ICUで治療を行った重症喘息発作患者13例について検討した。全13例中6例が初診時CPAOA(Cardiopulmonary Arrest)であった。11例において人工呼吸管理が必要であり、8例に対して吸入麻酔薬併用人工呼吸管理を行った。治療成績としては、13例中8例を救命した。死亡5例は全てCPAOA患者であった。人工呼吸管理を要し救命した6例中、吸入麻酔薬併用群3例と非併用群3例を比較すると併用群において、ステロイド投与量が多い傾向を示した。このことから、吸入麻酔併用人工呼吸管理により、最重症例を救命しえた可能性が示唆された。初診時CPAOAの患者は集学的治療に反応しなかった。よって、喘息急性増悪患者においては、初期治療を早期に開始することが重要と考えられた。(著者抄録)

われわれは縊頸症例の臨床経過を検討し,これらの転帰を左右する因子を見極めることを目的に,実験的に解明している病態生理を考察した.【対象と方法】1998.4〜2003.8に経験した自殺企図411例のうち,縊頸44例を対象として検討した.完遂率に関しては他の自殺企図手段と比較した.救急隊現場到着時(以下,現着時)cardiopulmonary arrest(CPA)の群とnon-CPA群に分け,転帰及び臨床経過を検討した.後者を来院時の意識障害の程度で2群に分け,年齢,男女比,縊頸形態,死亡率,社会復帰率,遅発性無酸素症後脳症の発症率に関して検討した.また,全縊頸症例において転帰を左右する因子として年齢,男女比,縊頸形態,現着時CPAの有無を取り上げその関与につき検討した.【結果】縊頸は検討期間の自殺企図手段の10.7%を占めるが,完遂率は75%と他の手段に比して最も高かった.現着時CPAの縊頸は33例あり,このうち7例に自己心拍の再開を認め,そのうち1例のみ社会復帰したが6例は死亡した.一方,現着時non-CPAは11例あり,死亡は1例,残り10例は社会復帰した.この11例には意識障害の程度で分類した2群間で背景因子や臨床経過・転帰に有意な差を認めなかった.また,全44例の転帰を左右する因子では,現着時CPAの有無にのみ有意差を認めた.【考察】縊頸で脳血流が途絶し,気道が閉塞すると,中枢神経系の不可逆的障害に次いで,心臓を含めた各臓器の固有機能が停止する.従って,現着時CPA症例の予後は不良であるとともに,CPAの有無が目撃者に乏しい縊頸の転帰を左右する唯一の因子となることが判明した.一方,自律神経反射にて短い経過時間でCPAに陥った症例では,早期に縊頸を解除し適切な処置を施行することで,速やかな心拍再開が見込まれ救命可能である.【結語】今回の検討結果を踏まえ,現着時CPAであった縊頸症例の治療に関しては,慎重に考慮する必要があると思われた(著者抄録)

研究期間中に外来を受診した院外心肺停止患者912例を対象に外来受診時のアンモニア血中濃度,乳酸血中濃度が生命予後を予測する因子になりえるか否かを検証した.多変量解析を用いて検証した結果,これら二つのbiomarkerは独立した予後予測因子になり得ることが分かった.また,自己心拍再開後24時間以内の神経学的予後予測因子の有用性も検証した.その結果,蘇生後24時間以内の早期神経学的予後予測因子として,S100BがIL-6やNSEよりも優れていることが分かった.