Organ donation after extracorporeal cardiopulmonary resuscitation: a nationwide retrospective cohort study.

BACKGROUND: Limited data are available on organ donation practices and recipient outcomes, particularly when comparing donors who experienced cardiac arrest and received extracorporeal cardiopulmonary resuscitation (ECPR) followed by veno-arterial extracorporeal membrane oxygenation (ECMO) decannulation, versus those who experienced cardiac arrest without receiving ECPR. This study aims to explore organ donation practices and outcomes post-ECPR to enhance our understanding of the donation potential after cardiac arrest. METHODS: We conducted a nationwide retrospective cohort study using data from the Japan Organ Transplant Network database, covering all deceased organ donors between July 17, 2010, and August 31, 2022. We included donors who experienced at least one episode of cardiac arrest. During the study period, patients undergoing ECMO treatment were not eligible for a legal diagnosis of brain death. We compared the timeframes associated with each donor's management and the long-term graft outcomes of recipients between ECPR and non-ECPR groups. RESULTS: Among 370 brain death donors with an episode of cardiac arrest, 26 (7.0%) received ECPR and 344 (93.0%) did not; the majority were due to out-of-hospital cardiac arrests. The median duration of veno-arterial ECMO support after ECPR was 3 days. Patients in the ECPR group had significantly longer intervals from admission to organ procurement compared to those not receiving ECPR (13 vs. 9 days, P = 0.005). Lung graft survival rates were significantly lower in the ECPR group (log-rank test P = 0.009), with no significant differences in other organ graft survival rates. Of 160 circulatory death donors with an episode of cardiac arrest, 27 (16.9%) received ECPR and 133 (83.1%) did not. Time intervals from admission to organ procurement following circulatory death and graft survival showed no significant differences between ECPR and non-ECPR groups. The number of organs donated was similar between the ECPR and non-ECPR groups, regardless of brain or circulatory death. CONCLUSIONS: This nationwide study reveals that lung graft survival was lower in recipients from ECPR-treated donors, highlighting the need for targeted research and protocol adjustments in post-ECPR organ donation.

Impact of sex of bystanders who perform cardiopulmonary resuscitation on return of spontaneous circulation in out-of-hospital cardiac arrest patients: A retrospective, observational study.

Background: The impact of the sex of bystanders who initiate cardiopulmonary resuscitation (CPR) on out-of-hospital cardiac arrest (OHCA) patients has not been fully elucidated. This study aims to investigate the association between the sex of bystanders who perform CPR and the clinical outcomes of OHCA patients in real-world clinical settings. Methods: We conducted a retrospective, observational study using data from the Okayama City Fire Department in Japan. Patients were categorized based on bystanders' sex. Our primary outcomes were return of spontaneous circulation (ROSC). Our secondary outcome was 30-day survival and 30-day favorable neurological outcome, defined as Cerebral Performance Category score of 1 or 2. Multivariable logistic regression analysis was used to examine the association between these groups and outcomes. Results: The study included 3,209 patients with a comparable distribution of male (1,540 patients: 48.0%) and female bystanders (1,669 patients: 52.0%) between the groups. Overall, 221 (6.9%) ROSC at hospital arrival, 226 (7.0%) patients had 30-day survival, and 121 (3.8%) patients had 30-day favorable neurological outcomes. Bystander sex (female as reference) did not contribute to ROSC at hospital arrival (adjusted OR [aOR] 1.11, 95% CI: 0.76-1.61), 30-day survival (aOR 1.23, 95% CI: 0.83-1.82), or 30-day favorable neurological outcomes (aOR 0.66, 95% CI: 0.34-1.27). Basic life support education experience was a bystander factor positively associated with ROSC. Patient factors positively associated with ROSC were initial shockable rhythm and witness of cardiac arrest. Conclusion: There were no differences in ROSC, 30-day survival, or 30-day neurological outcomes in OHCA patients based on bystander sex.

Successful Cardiac, Lung, and Kidney Transplantation from a Methanol-poisoned Donor.

Massive methanol exposure can lead to severe and detrimental effects that can result in death or brain death. As organs from patients with brain death after methanol ingestion are less likely to be recovered, these patients have been considered marginal donors. We present a case of successful multiple organ transplantation (heart, lungs, and kidneys) from a methanol-poisoned patient. Our experience illustrates that donor death from methanol intoxication does not preclude organ transplantation.

Hydrogen in Transplantation: Potential Applications and Therapeutic Implications.

Hydrogen gas, renowned for its antioxidant properties, has emerged as a novel therapeutic agent with applications across various medical domains, positioning it as a potential adjunct therapy in transplantation. Beyond its antioxidative properties, hydrogen also exerts anti-inflammatory effects by modulating pro-inflammatory cytokines and signaling pathways. Furthermore, hydrogen's capacity to activate cytoprotective pathways bolsters cellular resilience against stressors. In recent decades, significant advancements have been made in the critical medical procedure of transplantation. However, persistent challenges such as ischemia-reperfusion injury (IRI) and graft rejection continue to hinder transplant success rates. This comprehensive review explores the potential applications and therapeutic implications of hydrogen in transplantation, shedding light on its role in mitigating IRI, improving graft survival, and modulating immune responses. Through a meticulous analysis encompassing both preclinical and clinical studies, we aim to provide valuable insights into the promising utility of hydrogen as a complementary therapy in transplantation.

Changes in temporal muscle dimensions and their clinical impact in out-of-hospital cardiac arrest survivors.

Objective: This study investigates temporal muscle atrophy in out-of-hospital cardiac arrest patients post-resuscitation, seeking associations with neurological outcomes and factors associated with atrophy. Methods: Using data from six Japanese intensive care units, adult patients' post-resuscitation who underwent head computed tomography scans on admission and two to five days post-admission were assessed. Temporal muscle area, thickness, and density were quantified from a single cross-sectional image. Patients were categorized into 'atrophy' or 'no atrophy' groups based on median daily temporal muscle atrophy rates. The primary outcome was changes in temporal muscle dimensions between admission and follow-up two to five days later. Secondary outcomes included assessing the impact of temporal muscle atrophy on 30-day survival, as well as identifying any clinical factors associated with temporal muscle atrophy. Results: A total of 185 patients were analyzed. Measurements at follow-up revealed significant decreases in temporal muscle area (214 vs. 191 mm2, p < 0.001), thickness (4.9 vs. 4.7 mm, p < 0.001), and density (46 vs. 44 HU, p < 0.001) compared to those at admission. The median daily rate for temporal muscle area atrophy was 2.0% per day. There was no significant association between temporal muscle atrophy and 30-day survival (hazard ratios, 0.71; 95% CI, 0.41-1.23, p = 0.231). Multivariable logistic regression found no clinical factors significantly associated with temporal muscle atrophy. Conclusions: Temporal muscle atrophy in post-resuscitation patients occurs rapidly at 2.0% per day. However, there was no significant association with 30-day mortality or any identified clinical factors. Further investigation into its long-term functional implications is warranted.

Evaluation for Blood Concentration and Efficacy/Safety of Continuous Administration of Thiamylal in Children.

BACKGROUND: Thiamylal exerts excellent sedative effects. However, it is not routinely used because of its serious adverse effects. This study aimed to clarify the target blood concentration range and infusion rate of thiamylal in children by measuring its blood concentration and evaluating its relationship with efficacy and adverse effects. METHODS: This study was approved by the Ethics Committee of Japanese Red Cross Kumamoto Hospital. The authors included 10 children aged between 1 and 7 years who had received continuous intravenous (IV) infusion of thiamylal for the management of refractory status epilepticus, excluding those who met the exclusion criteria. After a 2 mg/kg bolus injection of thiamylal, continuous IV infusion was initiated at a rate of 2-3 mg/kg/h. Thiamylal concentration in the blood was measured using high-performance liquid chromatography. The State Behavioral Scale and the frequency of bolus injections were used to evaluate efficacy. Blood pressure and heart rate were measured to evaluate adverse effects. Statistical analyses of the time to awakening and the factors affecting it were also conducted. RESULTS: The State Behavioral Scale score during thiamylal administration was -2 or lower in all cases, suggesting that the depth of sedation was sufficient. The frequency of bolus injections decreased in a blood concentration-dependent manner, suggesting that the frequency tended to decrease, especially at thiamylal blood concentrations of 20 mcg/mL or higher. An increase of the infusion rate to 3 mg/kg/h was recommended, because the blood concentration may not reach 20 mcg/mL at an infusion rate of 2 mg/kg/h. There was also a case in which a rapid increase in blood concentration accompanied by a decrease in blood pressure and heart rate was observed when the infusion rate was increased to 4 mg/kg/h. Furthermore, the time to awakening after the end of administration correlated with the highest blood concentration during administration; therefore, delayed awakening was noted when using a high dose of thiamylal. CONCLUSIONS: The target blood concentration of thiamylal in children should be 20-30 mcg/mL, and the infusion rate should be based on 3 mg/kg/h.

Treatment patterns and clinician stress related to care of out-of-hospital cardiac arrest patients with a do not attempt resuscitation order.

Objective: This research investigated treatment patterns for out-of-hospital cardiac arrest patients with Do Not Attempt Resuscitation orders in Japanese emergency departments and the associated clinician stress. Methods: A cross-sectional survey was conducted at 9 hospitals in Okayama, Japan, targeting emergency department nurses and physicians. The questionnaire inquired about the last treated out-of-hospital cardiac arrest patient with a Do Not Attempt Resuscitation. We assessed emotional stress on a 0-10 scale and moral distress on a 1-5 scale among clinicians. Results: Of 208 participants, 107 (51%) had treated an out-of-hospital cardiac arrest patient with a Do Not Attempt Resuscitation order in the past 6 months. Of these, 65 (61%) clinicians used a "slow code" due to perceived futility in resuscitation (42/65 [65%]), unwillingness to terminate resuscitation upon arrival (38/65 [59%]), and absence of family at the time of patient's arrival (35/65 [54%]). Female clinicians had higher emotional stress (5 vs. 3; P = 0.007) and moral distress (3 vs. 2; P = 0.002) than males. Nurses faced more moral distress than physicians (3 vs. 2; P < 0.001). Adjusted logistic regression revealed that having performed a "slow code" (adjusted odds ratio, 5.09 [95% CI, 1.68-17.87]) and having greater ethical concerns about "slow code" (adjusted odds ratio, 0.35 [95% CI, 0.19-0.58]) were associated with high stress levels. Conclusions: The prevalent use of "slow code" for out-of-hospital cardiac arrest patients with Do Not Attempt Resuscitation orders underscores the challenges in managing these patients in clinical practice.

Radiation in an emergency situation: attempting to respect the patient's beliefs as reported by a minor.

BACKGROUND: Each individual's unique health-related beliefs can greatly impact the patient-clinician relationship. When there is a conflict between the patient's preferences and recommended medical care, it can create a serious ethical dilemma, especially in an emergency setting, and dramatically alter this important relationship. CASE PRESENTATION: A 56-year-old man, who remained comatose after out-of-hospital cardiac arrest, was rushed to our hospital. The patient was scheduled for emergency coronary angiography when his adolescent daughter reported that she and her father held sincere beliefs against radiation exposure. We were concerned that she did not fully understand the potential consequences if her father did not receive the recommended treatment. A physician provided her with in depth information regarding the risks and benefits of the treatment. While we did not want to disregard her statement, we opted to save the patient's life due to concerns about the validity of her report. CONCLUSIONS: Variations in beliefs regarding medical care force clinicians to incorporate patient beliefs into medical practice. However, an emergency may require a completely different approach. When faced with a patient in a life-threatening condition and unconscious, we should take action to prioritize saving their life, unless we are highly certain about the validity of their advance directives.

Hydrogen inhalation attenuates lung contusion after blunt chest trauma in mice.

BACKGROUND: Lung contusion caused by blunt chest trauma evokes a severe inflammatory reaction in the pulmonary parenchyma that may be associated with acute respiratory distress syndrome. Although hydrogen gas has antioxidant and anti-inflammatory effects and is protective against multiple types of lung injury at safe concentrations, the effects of inhaled hydrogen gas on blunt lung injury have not been previously investigated. Therefore, using a mouse model, we tested the hypothesis that hydrogen inhalation after chest trauma would reduce pulmonary inflammation and acute lung injury associated with lung contusion. METHODS: Inbred male C57BL/6 mice were randomly divided into 3 groups: sham with air inhalation, lung contusion with air inhalation, and lung contusion with 1.3% hydrogen inhalation. Experimental lung contusion was induced using a highly reproducible and standardized apparatus. Immediately after induction of lung contusion, mice were placed in a chamber exposed to 1.3% hydrogen gas in the air. Histopathological analysis and real-time polymerase chain reaction in lung tissue and blood gas analysis were performed 6 hours after contusion. RESULTS: Histopathological examination of the lung tissue after contusion revealed perivascular/intra-alveolar hemorrhage, perivascular/interstitial leukocyte infiltration, and interstitial/intra-alveolar edema. These histological changes and the extent of lung contusion, as determined by computed tomography, were significantly mitigated by hydrogen inhalation. Hydrogen inhalation also significantly reduced inflammatory cytokine and chemokine mRNA levels and improved oxygenation. CONCLUSION: Hydrogen inhalation therapy significantly mitigated inflammatory responses associated with lung contusion in mice. Hydrogen inhalation therapy may be a supplemental therapeutic strategy for treating lung contusion.

Successfully treated case of severe hypothermia secondary to myxedema coma.

Background: Myxedema coma is an extremely rare but fatal endocrine emergency that requires urgent recognition and treatment. We describe a case of severe hypothermia that rapidly deteriorated to cardiac arrest that was attributed to myxedema coma. Case Presentation: A 52-year-old man without a history of hypothyroidism was transferred to our emergency department due to coma and profound hypothermia. The patient developed cardiac arrest immediately after hospital arrival but return of spontaneous circulation was achieved shortly after resuscitation. The patient was noted to have generalized, nonpitting edema, dry skin, severe respiratory acidosis, hyponatremia, and elevated creatinine kinase, which was indicative of hypothyroidism. Myxedema coma was confirmed by a thyroid profile. The patient was successfully treated with intravenous levothyroxine and glucocorticoid. Conclusion: Although myxedema coma is a rare cause of severe hypothermia, emergency physicians should be familiar with its clinical features and management.

Association of Prehospital Physician Presence During Pediatric Out-of-Hospital Cardiac Arrest With Neurologic Outcomes.

OBJECTIVES: To examine the association of prehospital physician presence with neurologic outcomes of pediatric patients with out-of-hospital cardiac arrest (OHCA). DESIGN: Retrospective cohort study. SETTING: Data from the Japanese Association for Acute Medicine-OHCA Registry. INTERVENTIONS: None. PATIENTS: Pediatric patients (age 17 yr old or younger) registered in the database between June 2014 and December 2019. MEASUREMENT AND MAIN RESULTS: We used logistic regression models with stabilized inverse probability of treatment weighting (IPTW) to estimate the associated treatment effect of a prehospital physician with 1-month neurologically intact survival. Secondary outcomes included in-hospital return of spontaneous circulation (ROSC) and 1-month survival after OHCA. A total of 1,187 patients (276 in the physician presence group and 911 in the physician absence group) were included (median age 3 yr [interquartile range 0-14 yr]; 723 [61%] male). Comparison of the physician presence group, versus the physician absence, showed 1-month favorable neurologic outcomes of 8.3% (23/276) versus 3.6% (33/911). Physician presence was associated with greater odds of 1-month neurologically intact survival after stabilized IPTW adjustment (adjusted odds ratio [aOR] 1.98, 95% CI 1.08-3.66). We also found an association in the secondary outcome between physician presence, opposed to absence, and in-hospital ROSC (aOR 1.48, 95% CI 1.08-2.04). However, we failed to identify an association with 1-month survival (aOR 1.49, 95% CI 0.97-2.88). CONCLUSIONS: Among pediatric patients with OHCA, prehospital physician presence, compared with absence, was associated almost two-fold greater odds of 1-month favorable neurologic outcomes.

Organ Donation after Extracorporeal Cardiopulmonary Resuscitation and Brain Death.

A 38-year-old primipara Japanese woman suffered cardiac arrest due to a pulmonary thromboembolism 1 day after undergoing a cesarean section. Extracorporeal cardiopulmonary resuscitation was initiated and extracorporeal membrane oxygenation support was needed for 24 h. Despite intensive care, the patient was diagnosed with brain death on day 6. With the family's consent, comprehensive end-of-life care including organ donation was discussed based on our hospital's policy. The family decided to donate her organs. Specific training and education are required for emergency physicians to optimize the process of incorporating organ donation into end-of-life care while respecting the patient's and family's wishes.

Early-stage antibody kinetics after the third dose of BNT162b2 mRNA COVID-19 vaccination measured by a point-of-care fingertip whole blood testing.

Amid the Coronavirus Disease 2019 pandemic, we aimed to demonstrate the accuracy of the fingertip whole blood sampling test (FWT) in measuring the antibody titer and uncovering its dynamics shortly after booster vaccination. Mokobio SARS-CoV-2 IgM & IgG Quantum Dot immunoassay (Mokobio Biotechnology R&D Center Inc., MD, USA) was used as a point-of-care FWT in 226 health care workers (HCWs) who had received two doses of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) at least 8 months prior. Each participant tested their antibody titers before and after the third-dose booster up to 14-days. The effect of the booster was observed as early as the fourth day after vaccination, which exceeded the detection limit (> 30,000 U/mL) by 2.3% on the fifth day, 12.2% on the sixth day, and 22.5% after the seventh day. Significant positive correlations were observed between the pre- and post-vaccination (the seventh and eighth days) antibody titers (correlation coefficient, 0.405; p < 0.001). FWT is useful for examining antibody titers as a point-of-care test. Rapid response of antibody titer started as early as the fourth day post-vaccination, while the presence of weak responders to BNT162b2 vaccine was indicated.

Luminal administration of biliverdin ameliorates ischemia-reperfusion injury following intestinal transplant in rats.

BACKGROUND: Intestinal grafts are susceptible to ischemia-reperfusion injury, resulting in the loss of mucosal barrier function and graft failure. Biliverdin is known to exert a variety of cytoprotective functions against oxidative tissue injury. Because the mucosal layer is the primary site of ischemia-reperfusion injury, mucosa-targeting strategies by luminal delivery of reagents might be beneficial. We tested whether intraluminal administration of biliverdin as an adjuvant to standard preservation solutions protected against ischemia-reperfusion injury. METHODS: Orthotopic syngeneic intestinal transplants were performed on Lewis rats after 6 hours of cold preservation. Saline containing biliverdin (10 µM) or without biliverdin was introduced into the lumen of the intestinal grafts immediately before cold preservation. RESULTS: Damage to the intestinal mucosa caused by ischemia-reperfusion injury resulted in severe morphological changes, including blunting of the villi and erosion, and led to significant loss of gut barrier function 3 hours after reperfusion. These changes to the mucosa were notably ameliorated by intraluminal administration of biliverdin. Biliverdin also effectively inhibited upregulation of messenger RNAs for interleukin-6, inducible nitric oxide synthase, and C-C motif chemokine 2. Additionally, biliverdin treatment prevented the loss of expression of claudin-1, a transmembrane, tight-junction barrier protein. The 14-day survival of recipients of biliverdin-treated grafts was significantly improved as compared with the recipients of saline-treated control grafts (83.3% vs 38.9%, P = .030). CONCLUSION: This study demonstrated that luminally delivered biliverdin provides beneficial effects during the transplant of rat small intestinal grafts and could be an attractive therapeutic option in organ transplantation.

Can Blood Ammonia Level, Prehospital Time, and Return of Spontaneous Circulation Predict Neurological Outcomes of Out-of-Hospital Cardiac Arrest Patients? A Nationwide, Retrospective Cohort Study.

BACKGROUND: This study aimed to test if blood ammonia levels at hospital arrival, considering prehospital time and the patient's condition (whether return of spontaneous circulation [ROSC] was achieved at hospital arrival), can predict neurological outcomes after out-of-hospital cardiac arrest (OHCA). METHODS: This was a retrospective cohort study on data from a nationwide OHCA registry in Japan. Patients over 17 years old and whose blood ammonia levels had been recorded were included. The primary outcome was favorable neurological outcome at 30 days after OHCA. Blood ammonia levels, prehospital time, and the combination of the two were evaluated using the receiver operating characteristic curve to predict favorable outcomes. Then, cut-off blood ammonia values were determined based on whether ROSC was achieved at hospital arrival. RESULTS: Blood ammonia levels alone were sufficient to predict favorable outcomes. The overall cut-off ammonia value for favorable outcomes was 138 µg/dL; values were different for patients with ROSC (96.5 µg/dL) and those without ROSC (156 µg/dL) at hospital arrival. CONCLUSIONS: Our results using patient data from a large OHCA registry showed that blood ammonia levels at hospital arrival can predict neurological outcomes, with different cut-off values for patients with or without ROSC at hospital arrival.

Luminal Administration of a Water-soluble Carbon Monoxide-releasing Molecule (CORM-3) Mitigates Ischemia/Reperfusion Injury in Rats Following Intestinal Transplantation.

BACKGROUND: The protective effects of carbon monoxide (CO) against ischemia/reperfusion (IR) injury during organ transplantation have been extensively investigated. Likewise, CO-releasing molecules (CORMs) are known to exert a variety of pharmacological activities via liberation of controlled amounts of CO in organs. Therefore, we hypothesized that intraluminal administration of water-soluble CORM-3 during cold storage of intestinal grafts would provide protective effects against IR injury. METHODS: Orthotopic syngeneic intestinal transplantation was performed in Lewis rats following 6 h of cold preservation in Ringer solution or University of Wisconsin solution. Saline containing CORM-3 (100 µmol/L) or its inactive counterpart (iCORM-3) was intraluminally introduced in the intestinal graft before cold preservation. RESULTS: Histopathological analysis of untreated and iCORM-3-treated grafts revealed a similar erosion and blunting of the intestinal villi. These changes in the mucosa structure were significantly attenuated by intraluminal administration of CORM-3. Intestinal mucosa damage caused by IR injury led to considerable deterioration of gut barrier function 3 h postreperfusion. CORM-3 significantly inhibited upregulation of proinflammatory mRNA levels, ameliorated intestinal morphological changes, and improved graft blood flow and mucosal barrier function. Additionally, CORM-3-treated grafts increased recipient survival rates. Pharmacological blockade of soluble guanylyl cyclase activity significantly reversed the protective effects conferred by CORM-3, indicating that CO partially mediates its therapeutic actions via soluble guanylyl cyclase activation. CONCLUSIONS: Our study demonstrates that luminally delivered CORM-3 provides beneficial effects in cold-stored rat small intestinal grafts and could be an attractive therapeutic application of CO in the clinical setting of organ preservation and transplantation.

Adult Scurvy Presenting with Painful Purpura on the Legs.

Prolonged vitamin C deficiency can result in numerous metabolic abnormalities like impaired tissue repair and defective collagen synthesis. This case report describes a middle-age Japanese man presenting painful purpura on his lower limbs, severe anemia, and altered consciousness. The patient had been eating a selective diet lacking in vegetables and fruits since childhood. A serum analysis demonstrated a low level of vitamin C. The patient was treated with vitamin supplementation and psychological intervention. Scurvy is an under-considered illness with a favorable prognosis if diagnosed early while it is still sporadically encountered in some patients with malabsorption or malnutrition even in modern times.

Short or Irregular Sleep Duration in Early Childhood Increases Risk of Injury for Primary School-Age Children: A Nationwide Longitudinal Birth Cohort in Japan.

The aim of this study was to investigate the longitudinal relationship between shorter or irregular sleep duration (SD) in early childhood and increased risk of injury at primary school age using data from a nationwide survey in Japan. We categorized SD into seven groups: 6 h, 7 h, 8 h, 9 hrs, 10 or 11 h, >12 h, and irregular, based on questionnaire responses collected at 5.5 years old. The relationship between SD and incidence of injury at 5.5-nine years of age is shown. In addition, we completed a stratified analysis on children with or without problematic behavior at eight years old. We included 32,044 children, of which 6369 were classified as having an injury and 25,675 as not having an injury. Logistic regression model showed that shorter or irregular SD categories were associated with an increased adjusted odds ratio (aOR) for injuries (6 h: aOR 1.40, 95% confidence interval (CI) 1.19-1.66, 7 h: aOR 1.10, 95% CI, 0.98-1.23, 8 h: aOR 1.13, 95% CI, 1.02-1.26, irregular: aOR 1.26, 95% CI 1.10-1.43). The same tendency was observed with shorter or irregular SD in subgroups with or without behavioral problems. Shorter or irregular sleep habits during early childhood are associated with injury during primary school age.