Life-Threatening Hematuria as Initial Presentation of a Complicated Transplant Renal Artery Pseudoaneurysm.

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.

COVID-19-Associated Portal Vein Thrombosis Post-Cholecystitis.

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.

The role of pyruvate-induced enhancement of oxygen metabolism in extracellular purinergic signaling in the post-cardiac arrest rat model.

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.

Association between time-dependent changes in cerebrovascular autoregulation after cardiac arrest and outcomes: A prospective cohort study.

This prospective observational single-center cohort study aimed to determine an association between cerebrovascular autoregulation (CVAR) and outcomes in hypoxic-ischemic brain injury post-cardiac arrest (CA), and assessed 100 consecutive post-CA patients in Japan between June 2017 and May 2020 who experienced a return of spontaneous circulation. Continuous monitoring was performed for 96 h to determine CVAR presence. A moving Pearson correlation coefficient was calculated from the mean arterial pressure and cerebral regional oxygen saturation. The association between CVAR and outcomes was evaluated using the Cox proportional hazard model; non-CVAR time percent was the time-dependent, age-adjusted covariate. The non-linear effect of target temperature management (TTM) was assessed using a restricted cubic spline. Of the 100 participants, CVAR was detected using the cerebral performance category (CPC) in all patients with a good neurological outcome (CPC 1-2) and in 65 patients (88%) with a poor outcome (CPC 3-5). Survival probability decreased significantly with increasing non-CVAR time percent. The TTM versus the non-TTM group had a significantly lower probability of a poor neurological outcome at 6 months with a non-CVAR time of 18%-37% (p < 0.05). Longer non-CVAR time may be associated with significantly increased mortality in hypoxic-ischemic brain injury post-CA.

Multi-Drug Cocktail Therapy Improves Survival and Neurological Function after Asphyxial Cardiac Arrest in Rodents.

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.

External Stenting (Exostenting) to Correct Vascular Torsion and Angulation.

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.

Insufficient oxygen inhalation during cardiopulmonary resuscitation induces early changes in hemodynamics followed by late and unfavorable systemic responses in post-cardiac arrest rats.

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.

Exogenous mitochondrial transplantation improves survival and neurological outcomes after resuscitation from cardiac arrest.

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.

Bio-physiological susceptibility of the brain, heart, and lungs to systemic ischemia reperfusion and hyperoxia-induced injury in post-cardiac arrest rats.

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.

A prehospital risk assessment tool predicts clinical outcomes in hospitalized patients with heat-related illness: a Japanese nationwide prospective observational study.

We previously developed a risk assessment tool to predict outcomes after heat-related illness (J-ERATO score), which consists of six binary prehospital vital signs. We aimed to evaluate the ability of the score to predict clinical outcomes for hospitalized patients with heat-related illnesses. In a nationwide, prospective, observational study, adult patients hospitalized for heat-related illnesses were registered. A binary logistic regression model and receiver operating characteristic (ROC) curve analysis were used to assess the relationship between the J-ERATO and survival at hospital discharge as a primary outcome. Among eligible patients, 1244 (93.0%) survived to hospital discharge. Multivariable logistic regression analysis revealed that the J-ERATO was an independent predictor for survival to discharge (adjusted odds ratio [OR] 0.47; 95% confidence interval [CI] 0.37-0.59) and occurrence of disseminated intravascular coagulation (DIC) on day 1 (adjusted OR 2.07; 95% CI 1.73-2.49). ROC analyses revealed an optimal J-ERATO cut-off of 5 for prediction of mortality at discharge (area under the curve [AUC] 0.742; 95% CI 0.691-0.787) and DIC development on day 1 (AUC 0.723; 95% CI 0.684-0.758). The J-ERATO obtained before transportation could be helpful in predicting the severity and mortality of hospitalized patients with heat-related illnesses.

Diagnostic value of transpulmonary thermodilution measurements for acute respiratory distress syndrome in a pig model of septic shock.

BACKGROUND: No direct approach assessing pulmonary vascular permeability exists in the current therapeutic strategy for patients with acute respiratory distress syndrome (ARDS). Transpulmonary thermodilution measures hemodynamic parameters such as pulmonary vascular permeability index and extravascular lung water, enabling clinicians to assess ARDS severity. The aim of this study is to explore a precise transpulmonary thermodilution-based criteria for quantifying the severity of lung injury using a clinically relevant septic-ARDS pig model. METHODS: Thirteen female pigs (weight: 31 ± 2 kg) were intubated, mechanically ventilated under anesthesia, and either assigned to septic shock-induced ARDS or control group. To confirm the development of ARDS, we performed computed tomography (CT) imaging in randomly selected animals. The pulmonary vascular permeability index, extravascular lung water, and other hemodynamic parameters were consecutively measured during the development of septic lung injury. Lung status was categorized as normal (partial pressure of oxygen/fraction of inspired oxygen ≥ 400), or injured at different degrees: pre-ARDS (300-400), mild-to-moderate ARDS (100-300), or severe ARDS (< 100). We also measured serum inflammatory cytokines and high mobility group box 1 levels during the experiment to explore the relationship of the pulmonary vascular permeability index with these inflammatory markers. RESULTS: Using CT image, we verified that animals subjected to ARDS presented an extent of consolidation in bilateral gravitationally dependent gradient that expands over time, with diffuse ground-glass opacification. Further, the post-mortem histopathological analysis for lung tissue identified the key features of diffuse alveolar damage in all animals subjected to ARDS. Both pulmonary vascular permeability index and extravascular lung water increased significantly, according to disease severity. Receiver operating characteristic analysis demonstrated that a cut-off value of 3.9 for the permeability index provided optimal sensitivity and specificity for predicting severe ARDS (area under the curve: 0.99, 95% confidence interval, 0.98-1.00; sensitivity = 100%, and specificity = 92.5%). The pulmonary vascular permeability index was superior in its diagnostic value than extravascular lung water. Furthermore, the pulmonary vascular permeability index was significantly associated with multiple parameters reflecting clinicopathological changes in animals with ARDS. CONCLUSION: The pulmonary vascular permeability index is an effective indicator to measure septic ARDS severity.

Transplant Renal Artery Stenosis Revascularization: Common Distal External Iliac Bypass.

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.

Sepsis-associated hypoglycemia on admission is associated with increased mortality in intensive care unit patients.

AIM: Hyperglycemia is a common response to acute illness, but it is not often seen in critical conditions. The frequency and cause of hypoglycemia in septic patients have not been well elucidated. In this study, we focused on sepsis-associated hypoglycemia in the early phase and evaluated the impact of hypoglycemia on mortality. METHODS: We performed a retrospective review of 265 patients with sepsis admitted to a tertiary medical center. Blood glucose levels on admission were evaluated and analyzed by a Cox proportional hazard model. RESULTS: We categorized patients with sepsis into five groups according to blood glucose levels. Seven patients (2.6%) were admitted with severe hypoglycemia (≤40 mg/dL), 19 (7.2%) with mild hypoglycemia (41-70 mg/dL), 103 (38.9%) with euglycemia (71-140 mg/dL), 58 (21.9%) with mild hyperglycemia (141-180 mg/dL), and 78 (29.4%) with hyperglycemia (>180 mg/dL). There was a significant difference in 28-day mortality between those with severe hypoglycemia and euglycemia (71.4% versus 8.7%; P < 0.05). We analyzed the hazard ratios for the groups (relative to the reference of euglycemia) adjusted for sex, age, and Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores on admission. The hazard ratios for 28-day mortality in patients with severe hypoglycemia and mild hypoglycemia compared with that in patients with euglycemia were 8.18 (95% confidence interval [CI], 2.39-27.96; P = 0.001) and 7.56 (95% CI, 2.96-19.35; P < 0.001), respectively. CONCLUSION: Septic patients with severe hypoglycemia had significantly higher mortality compared with patients with euglycemia.

Preserving Brain LPC-DHA by Plasma Supplementation Attenuates Brain Injury after Cardiac Arrest.

OBJECTIVE: Cardiac arrest (CA) is a major health burden with brain damage being a significant contributor to mortality. We found lysophosphatidylcholine (LPC), including a species containing docosahexaenoic acid (LPC-DHA), was significantly decreased in plasma post-CA, supplementation of which significantly improved neurological outcomes. The aim of this study is to understand the protective role of LPC-DHA supplementation on the brain post-CA. METHODS: We first evaluated associations between the plasma level of LPC-DHA and neurological injury and outcomes of human patients with CA. We then utilized a rat CA model and cell cultures to investigate therapeutic and mechanistic aspects of plasma LPC-DHA supplementation. RESULTS: We found that decreased plasma LPC-DHA was strongly associated with neurological outcomes and disappearance of the difference between gray and white matter in the brain after CA in human patients. In rats, the decreased plasma LPC-DHA was associated with decreased levels of brain LPC-DHA after CA, and supplementing plasma LPC-DHA normalized brain levels of LPC-DHA and alleviated neuronal cell death, activation of astrocytes, and expression of various inflammatory and mitochondrial dynamics genes. We also observed deceased severity of metabolic alterations with LPC-DHA supplementation using untargeted metabolomics analysis. Furthermore, LPC treatment showed a similar protective effect for neurons and astrocytes in mixed primary brain cell cultures. INTERPRETATION: The observed neuroprotection accompanied with normalized brain LPC-DHA level by plasma supplementation implicate the importance of preventing the decrease of brain LPC-DHA post-CA for attenuating brain injury. Furthermore, the data supports the causative role of decreased plasma LPC-DHA for brain damage after CA. ANN NEUROL 2022;91:389-403.

Phospholipid Screening Postcardiac Arrest Detects Decreased Plasma Lysophosphatidylcholine: Supplementation as a New Therapeutic Approach.

OBJECTIVES: Cardiac arrest and subsequent resuscitation have been shown to deplete plasma phospholipids. This depletion of phospholipids in circulating plasma may contribute to organ damage postresuscitation. Our aim was to identify the diminishment of essential phospholipids in postresuscitation plasma and develop a novel therapeutic approach of supplementing these depleted phospholipids that are required to prevent organ dysfunction postcardiac arrest, which may lead to improved survival. DESIGN: Clinical case control study followed by translational laboratory study. SETTING: Research institution. PATIENTS/SUBJECTS: Adult cardiac arrest patients and male Sprague-Dawley rats. INTERVENTIONS: Resuscitated rats after 10-minute asphyxial cardiac arrest were randomized to be treated with lysophosphatidylcholine specie or vehicle. MEASUREMENTS AND MAIN RESULTS: We first performed a phospholipid survey on human cardiac arrest and control plasma. Using mass spectrometry analysis followed by multivariable regression analyses, we found that plasma lysophosphatidylcholine levels were an independent discriminator of cardiac arrest. We also found that decreased plasma lysophosphatidylcholine was associated with poor patient outcomes. A similar association was observed in our rat model, with significantly greater depletion of plasma lysophosphatidylcholine with increased cardiac arrest time, suggesting an association of lysophosphatidylcholine levels with injury severity. Using a 10-minute cardiac arrest rat model, we tested supplementation of depleted lysophosphatidylcholine species, lysophosphatidylcholine(18:1), and lysophosphatidylcholine(22:6), which resulted in significantly increased survival compared with control. Furthermore, the survived rats treated with these lysophosphatidylcholine species exhibited significantly improved brain function. However, supplementing lysophosphatidylcholine(18:0), which did not decrease in the plasma after 10-minute cardiac arrest, had no beneficial effect. CONCLUSIONS: Our data suggest that decreased plasma lysophosphatidylcholine is a major contributor to mortality and brain damage postcardiac arrest, and its supplementation may be a novel therapeutic approach.

Monitoring the tissue perfusion during hemorrhagic shock and resuscitation: tissue-to-arterial carbon dioxide partial pressure gradient in a pig model.

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.

Hydrogen gas with extracorporeal cardiopulmonary resuscitation improves survival after prolonged cardiac arrest in rats.

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.

Dynamic changes of the hemoglobin index during resuscitation in patients with out-of-hospital cardiopulmonary arrest due to freshwater drowning: A retrospective observational study.

BACKGROUND: The hemoglobin index (HbI) represents the amount of hemoglobin, which reflects the regional tissue blood volume. The HbI is calculated by a regional oxygen saturation monitor. In freshwater drowning, inhaled water is immediately absorbed into the blood causing hemodilution. We hypothesized that this blood dilution could be observed in real time using HbI values in patients with out-of-hospital cardiac arrest (OHCA) due to freshwater drowning. METHODS: In this single-center retrospective, observational study, we examined the HbI in patients with OHCA due to freshwater drowning from April 2015 to May 2020. Patients with OHCA due to hanging were selected as a control group. RESULTS: Thirty-two patients in the freshwater drowning group and 21 in the control group were eligible for inclusion. In the freshwater drowning group, the HbI values in the return of spontaneous circulation (ROSC) group were significantly decreased in comparison to the non-ROSC group (-0.28 [IQR -0.55, -0.12] vs. -0.04 [IQR -0.16, 0.025]; p = 0.024). In the control group, the change of HbI during resuscitation in the ROSC and non-ROSC groups was not significantly different (0.11 [IQR -0.3525, 0.4225] vs. -0.02 [IQR -0.14, 0.605]; p = 0.8228). In each patient with ROSC in the freshwater drowning group, the HbI value after ROSC was significantly decreased in comparison to before ROSC (1.2±0.5 vs. 0.9±0.5]; p = 0.0156). In contrast, this difference was not observed in patients with an ROSC in the control group (3.7±1.3 vs. 3.8±1.4]; p = 0.7940). CONCLUSION: Blood dilution induced by freshwater drowning might be detected in real time using the HbI. To prove the validity of this research's result, further prospective large study is needed.

Effectiveness of near-infrared spectroscopy-guided continuous chest compression resuscitation without rhythm check in patients with out-of-hospital cardiac arrest: The prospective multicenter TripleCPR 16 study.

BACKGROUND: The proportion of adult patients with return of spontaneous circulation (ROSC) following out-of-hospital cardiac arrest (OHCA) remains unchanged since 2012. A better resuscitation strategy is needed. This study evaluated the effectiveness of a regional cerebral oxygen saturation (rSO2)-guided resuscitation protocol without rhythm check based on our previous study. METHODS: Because defibrillation is the definitive therapy that should be performed without delay for shockable rhythm, the study subjects were OHCA patients with non-shockable rhythm on hospital arrival at three emergency departments. They were divided into three groups based on their baseline rSO2 value (%): ≥50, ≥40 to <50, or <40. Continuous chest compression without rhythm checks was performed for 16 minutes or until a maximum increase in rSO2 of 10%, 20%, or 35% was achieved in each group, respectively. This intervention cohort was compared with a historical control cohort regarding the probability of ROSC using inverse probability of treatment weighting (IPTW) with propensity score. RESULTS: The control and intervention cohorts respectively included 86 and 225 patients. The rate of ROSC was not significantly different between the groups (adjusted OR 0.91 [95% CI, 0.64-1.29], P = 0.60), but no serious adverse events occurred. Sensitivity analyses 1 and 2 showed a significant difference or positive tendency for higher probability of ROSC (adjusted OR 1.63 [95% CI, 1.22-2.17], P < 0.001) (adjusted OR 1.25 [95% CI, 0.95-1.63], P = 0.11). CONCLUSIONS: This trial suggested that a new cardiopulmonary resuscitation protocol with different rhythm check timing could be created using the rSO2 value. Clinical trial number: UMIN000025684.

Usefulness of simultaneous measurement of brain and muscle regional oxygen saturation in shock patients: A report of three cases.

The regional oxygen saturation (rSO2) values of brain and muscle tissues can be measured simultaneously even if blood pressure cannot be measured due to circulatory failure associated with shock and may continuously reflect the oxygen supply-demand balance.