Phosphoinositide-3-Kinase/Akt-Endothelial Nitric Oxide Synthase Signaling Pathway Mediates the Neuroprotective Effect of Sevoflurane Postconditioning in a Rat Model of Hemorrhagic Shock and Resuscitation.

BACKGROUND: Although extensive reports have demonstrated the neuroprotection of sevoflurane postconditioning in cases of focal and global cerebral ischemia/reperfusion, the underlying mechanisms are not completely elucidated. This study investigated whether this effect is related to endothelial nitric oxide synthase (eNOS) and mediated by the phosphoinositide-3-kinase pathway in a rat model of hemorrhagic shock and resuscitation. METHODS: Adult male Sprague Dawley rats were subjected to hemorrhagic shock for 60 minutes and then resuscitation for 30 minutes in experimental groups. Sevoflurane postconditioning was performed at the beginning of resuscitation to completion. At 24 hours after resuscitation, the brain infarct volume was evaluated by 2,3,5-triphenyltetrazolium chloride staining. The neuronal morphological changes and apoptosis were determined by hematoxylin and eosin staining and immunohistochemistry analysis, respectively. The activity of phosphorylated Akt and eNOS was evaluated by Western blot analysis. RESULTS: Brain injuries such as the cerebral infarct volume and pathological neuronal changes as well as cell apoptosis were observed in the hippocampus after hemorrhagic shock and resuscitation. Postconditioning with 2.4% sevoflurane significantly attenuated brain injuries. Wortmannin prevented the improvements of neuronal characteristics elicited by sevoflurane postconditioning as well as the hyperactivity of eNOS and phosphorylated Akt. CONCLUSIONS: Sevoflurane postconditioning could attenuate brain injury induced by hemorrhagic shock and resuscitation, and this neuroprotective effect may be partly by upregulation of eNOS through the phosphoinositide-3-kinase/Akt signaling pathway.

Resuscitative endovascular balloon occlusion of the aorta in combat casualties: The past, present, and future.

BACKGROUND: Noncompressible torso hemorrhage is a leading cause of preventable death on the battlefield. Intra-aortic balloon occlusion was first used in combat in the 1950s, but military use was rare before Operation Iraqi Freedom and Operation Enduring Freedom. During these wars, the combination of an increasing number of deployed vascular surgeons and a significant rise in deaths from hemorrhage resulted in novel adaptations of resuscitative endovascular balloon occlusion of the aorta (REBOA) technology, increasing its potential application in combat. We describe the background of REBOA development in response to a need for minimally invasive intervention for hemorrhage control and provide a detailed review of all published cases (n = 47) of REBOA use for combat casualties. The current limitations of REBOA are described, including distal ischemia and reperfusion injury, as well as ongoing research efforts to adapt REBOA for prolonged use in the austere setting. LEVEL OF EVIDENCE: Level V.

Management of sepsis and septic shock in the emergency department.

Early management of sepsis and septic shock is crucial for patients' prognosis. As the Emergency Department (ED) is the place where the first medical contact for septic patients is likely to occur, emergency physicians play an essential role in the early phases of patient management, which consists of accurate initial diagnosis, resuscitation, and early antibiotic treatment. Since the issuing of the Surviving Sepsis Campaign guidelines in 2016, several studies have been published on different aspects of sepsis management, adding a substantial amount of new information on the pathophysiology and treatment of sepsis and septic shock. In light of this emerging evidence, the present narrative review provides a comprehensive account of the recent advances in septic patient management in the ED.

Variation in acute fluid resuscitation among pediatric burn centers.

BACKGROUND: Accurate resuscitation of pediatric patients with large thermal injury is critical to achieving optimal outcomes. The goal of this project was to describe the degree of variability in resuscitation guidelines among pediatric burn centers and the impact on fluid estimates. METHODS: Five pediatric burn centers in the Pediatric Injury Quality Improvement Collaborative (PIQIC) contributed data from patients with ≥15% total body surface area (TBSA) burns treated from 2014 to 2018. Each center's resuscitation guidelines and guidelines from the American Burn Association were used to calculate estimated 24-h fluid requirements and compare these values to the actual fluid received. RESULTS: Differences in the TBSA burn at which fluid resuscitation was initiated, coefficients related to the Parkland formula, criteria to initiate dextrose containing fluids, and urine output goals were observed. Three of the five centers' resuscitation guidelines produced statistically significant lower mean fluid estimates when compared with the actual mean fluid received for all patients across centers (4.53 versus 6.35ml/kg/% TBSA, p<0.001), (4.90 versus 6.35ml/kg/TBSA, p=0.002) and (3.38 versus 6.35ml/kg/TBSA, p<0.0001). CONCLUSIONS: This variation in practice patterns led to statistically significant differences in fluid estimates. One center chose to modify its resuscitation guidelines at the conclusion of this study.

A Decade of Damage Control Resuscitation: New Transfusion Practice, New Survivors, New Directions.

OBJECTIVE: The aim of this study was to identify the effects of recent innovations in trauma major hemorrhage management on outcome and transfusion practice, and to determine the contemporary timings and patterns of death. BACKGROUND: The last 10 years have seen a research-led change in hemorrhage management to damage control resuscitation (DCR), focused on the prevention and treatment of trauma-induced coagulopathy. METHODS: A 10-year retrospective analysis of prospectively collected data of trauma patients who activated the Major Trauma Centre's major hemorrhage protocol (MHP) and received at least 1 unit of red blood cell transfusions (RBC). RESULTS: A total of 1169 trauma patients activated the MHP and received at least 1 unit of RBC, with similar injury and admission physiology characteristics over the decade. Overall mortality declined from 45% in 2008 to 27% in 2017, whereas median RBC transfusion rates dropped from 12 to 4 units (massive transfusion rates from 68% to 24%). The proportion of deaths within 24 hours halved (33%-16%), principally with a fall in mortality between 3 and 24 hours (30%-6%). Survivors are now more likely to be discharged to their own home (57%-73%). Exsanguination is still the principal cause of early deaths, and the mortality associated with massive transfusion remains high (48%). Late deaths are now split between those due to traumatic brain injury (52%) and multiple organ dysfunction (45%). CONCLUSIONS: There have been remarkable reductions in mortality after major trauma hemorrhage in recent years. Mortality rates continue to be high and there remain important opportunities for further improvements in these patients.

The management of the poisoned patient using a novel emergency department-based resuscitation and critical care unit (ResCCU).

OBJECTIVES: The Resuscitation & Critical Care Unit (ResCCU) is a novel ED-based ICU designed to provide early critical care services. This study sought to identify characteristics of poisoned patients treated in the ResCCU. METHODS: We conducted a retrospective, single-center case study of poisoned patients over the age of 18 years old over a 16-month period. Patient demographics, drug concentrations, and severity of illness scores were extracted from electronic medical records. Patients were divided into two groups, those who required short term ICU level care (< 24 h) and prolonged ICU care (> 24 h). RESULTS: A total of 58 ED visits with a tox-related illness were analyzed. There were 24 women (41%) and 34 men (59%). There were 42 patients (72%) who required short term ICU level care and 16 patients (28%) who required prolonged ICU care. In the short-term ICU group, 13 patients (31%) were discharged home directly from the ResCCU, 29 patients (69%) were sent to the inpatient floor, and 1 of the admitted floor patients expired. There were no patients admitted to the floor that required a step-up to the inpatient ICU. 56 patients (97%) were alive at post-admit day 7 and 28, and only 8 (14%) were re-admitted within 30 days. CONCLUSIONS: Patients who were treated in the ED-based ICU for toxicology-related illnesses were frequently able to be either discharged home or admitted to a regular floor after their initial stabilization and treatment, and none that were sent to the floor required an ICU step-up.

Administration of inhaled noble and other gases after cardiopulmonary resuscitation: A systematic review.

OBJECTIVE: Inhalation of noble and other gases after cardiac arrest (CA) might improve neurological and cardiac outcomes. This article discusses up-to-date information on this novel therapeutic intervention. DATA SOURCES: CENTRAL, MEDLINE, online published abstracts from conference proceedings, clinical trial registry clinicaltrials.gov, and reference lists of relevant papers were systematically searched from January 1960 till March 2019. STUDY SELECTION: Preclinical and clinical studies, irrespective of their types or described outcomes, were included. DATA EXTRACTION: Abstract screening, study selection, and data extraction were performed by two independent authors. Due to the paucity of human trials, risk of bias assessment was not performed DATA SYNTHESIS: After screening 281 interventional studies, we included an overall of 27. Only, xenon, helium, hydrogen, and nitric oxide have been or are being studied on humans. Xenon, nitric oxide, and hydrogen show both neuroprotective and cardiotonic features, while argon and hydrogen sulfide seem neuroprotective, but not cardiotonic. Most gases have elicited neurohistological protection in preclinical studies; however, only hydrogen and hydrogen sulfide appeared to preserve CA1 sector of hippocampus, the most vulnerable area in the brain for hypoxia. CONCLUSION: Inhalation of certain gases after CPR appears promising in mitigating neurological and cardiac damage and may become the next successful neuroprotective and cardiotonic interventions.

Contemporary resuscitation of hemorrhagic shock: What will the future hold?

Resuscitation of the critically ill patient with fluid and blood products is one of the most widespread interventions in medicine. This is especially relevant for trauma patients, as hemorrhagic shock remains the most common cause of preventable death after injury. Consequently, the study of the ideal resuscitative product for patients in shock has become an area of great scientific interest and investigation. Recently, the pendulum has swung towards increased utilization of blood products for resuscitation. However, pathogens, immune reactions and the limited availability of this resource remain a challenge for clinicians. Technologic advances in pathogen reduction and innovations in blood product processing will allow us to increase the safety profile and efficacy of blood products, ultimately to the benefit of patients. The purpose of this article is to review the current state of blood product based resuscitative strategies as well as technologic advancements that may lead to safer resuscitation.

Not Crying After Birth as a Predictor of Not Breathing.

BACKGROUND: Worldwide, every year, 6 to 10 million infants require resuscitation at birth according to estimates based on limited data regarding "nonbreathing" infants. In this article, we aim to describe the incidence of "noncrying" and nonbreathing infants after birth, the need for basic resuscitation with bag-and-mask ventilation, and death before discharge. METHODS: We conducted an observational study of 19 977 infants in 4 hospitals in Nepal. We analyzed the incidence of noncrying or nonbreathing infants after birth. The sensitivity of noncrying infants with nonbreathing after birth was analyzed, and the risk of predischarge mortality between the 2 groups was calculated. RESULTS: The incidence of noncrying infants immediately after birth was 11.1%, and the incidence of noncrying and nonbreathing infants was 5.2%. Noncrying after birth had 100% sensitivity for nonbreathing infants after birth. Among the "noncrying but breathing" infants, 9.5% of infants did not breathe at 1 minute and 2% did not to breathe at 5 minutes. Noncrying but breathing infants after birth had almost 12-fold odds of predischarge mortality (adjusted odds ratio 12.3; 95% confidence interval, 5.8-26.1). CONCLUSIONS: All nonbreathing infants after birth do not cry at birth. A proportion of noncrying but breathing infants at birth are not breathing by 1 and 5 minutes and have a risk for predischarge mortality. With this study, we provide evidence of an association between noncrying and nonbreathing. This study revealed that noncrying but breathing infants require additional care. We suggest noncrying as a clinical sign for initiating resuscitation and a possible denominator for measuring coverage of resuscitation.

Neonatal Resuscitation and Postresuscitation Care of Infants Born to Mothers with Suspected or Confirmed SARS-CoV-2 Infection.

The first case of novel coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was reported in November2019. The rapid progression to a global pandemic of COVID-19 has had profound medical, social, and economic consequences. Pregnant women and newborns represent a vulnerable population. However, the precise impact of this novel virus on the fetus and neonate remains uncertain. Appropriate protection of health care workers and newly born infants during and after delivery by a COVID-19 mother is essential. There is some disagreement among expert organizations on an optimal approach based on resource availability, surge volume, and potential risk of transmission. The manuscript outlines the precautions and steps to be taken before, during, and after resuscitation of a newborn born to a COVID-19 mother, including three optional variations of current standards involving shared-decision making with parents for perinatal management, resuscitation of the newborn, disposition, nutrition, and postdischarge care. The availability of resources may also drive the application of these guidelines. More evidence and research are needed to assess the risk of vertical and horizontal transmission of SARS-CoV-2 and its impact on fetal and neonatal outcomes. KEY POINTS: · The risk of vertical transmission is unclear; transmission from family members/providers to neonates is possible.. · Optimal personal-protective-equipment (airborne vs. droplet/contact precautions) for providers is crucial to prevent transmission.. · Parents should be engaged in shared decision-making with options for rooming in, skin-to-skin contact, and breastfeeding..

Heterogeneity of Cardiovascular Response to Standardized Sepsis Resuscitation.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2020. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.

Impact of the Revised NRP Meconium Aspiration Guidelines on Term Infant Outcomes.

OBJECTIVES: To evaluate the association of the Neonatal Resuscitation Program, Seventh Edition changes on term infants born with meconium-stained amniotic fluid (MSAF). STUDY DESIGN: We evaluated the effect of no longer routinely intubating nonvigorous term infants born with MSAF in 14 322 infants seen by the resuscitation team from January 1, 2014 to June 30, 2017 in a large, urban, academic hospital. RESULTS: Delivery room intubations of term infants with MSAF fell from 19% to 3% after the change in guidelines (P = <.0001). The rate of all other delivery room intubations also decreased by 3%. After the implementation of the Seventh Edition guidelines, 1-minute Apgar scores were significantly more likely to be >3 (P = .009) and significantly less likely to be <7 (P = .011). The need for continued respiratory support after the first day of life also decreased. Admission rates to the NICU, length of stay, and the need for respiratory support on admission were unchanged. CONCLUSIONS: Implementation of the Neonatal Resuscitation Program, Seventh Edition recommendations against routine suctioning nonvigorous infants born with MSAF was temporally associated with an improvement in 1-minute Apgar scores and decreased the need for respiratory support after the first day of life. There was also a significant decrease in total intubations performed in the delivery room. This has long-term implications on intubation experience among frontline providers.

Adequacy of Preoperative Resuscitation in Laparoscopic Pyloromyotomy and Anesthetic Emergence.

BACKGROUND: Pyloromyotomy is one of the most common surgical procedures performed on otherwise healthy infants. Pyloric stenosis results in a hypochloremic, hypokalemic metabolic alkalosis that is considered a medical emergency. This alkalotic state is believed to be associated with an increased incidence of apneic episodes. Because apnea tends to occur during anesthetic emergence, we sought to examine the association between the preoperative serum bicarbonate level and anesthetic emergence time after laparoscopic pyloromyotomy. METHODS: Data were collected from patients who underwent laparoscopic pyloromyotomies from April 2014 to October 2018. To estimate the correlation between preoperative bicarbonate level and emergence time while accounting for the positive skew of emergence time and potential confounding variables, a weighted quantile mixed regression was used. Due to a nonlinear association with emergence time, preoperative serum bicarbonate was split into 2 continuous intervals (<24 and ≥24 mEq/L) and the slope versus outcome was fit for each interval. RESULTS: A total of 529 patients who underwent laparoscopic pyloromyotomy were analyzed in this study. After controlling for confounders, the preoperative serum bicarbonate interval of ≥24 mEq/L was linearly associated with median emergence time (median increase of 0.81 minutes per 1 mEq/L increase of bicarbonate; 95% confidence interval [CI], 0.42-1.20; P < .001). Only 3 patients (0.6%) had apneic episodes after pyloromyotomy despite all having preoperative serum bicarbonate levels <29 mEq/L. CONCLUSIONS: Preoperative serum bicarbonate was positively associated with median anesthetic emergence time in a linear manner for values ≥24 mEq/L, although this correlation may not appear to be clinically substantial per 1 mEq/L unit. However, when preoperative serum bicarbonate levels were dichotomized at a commonly used presurgical threshold, the difference in median emergence time between ≥30 and <30 mEq/L was an estimated 5.4 minutes (95% CI, 3.1-7.8 minutes; P < .001).

Fluid volumes infused during burn resuscitation 1980-2015: A quantitative review.

INTRODUCTION: 'Fluid creep' or excessive fluid delivered to burn patients during early resuscitation has been suggested by several studies from individual burn centers. METHODS: We performed a Medline search from 1980 to 2015 in order to identify studies of burn patients predominantly resuscitated with lactated Ringers with infusion adjusted per urinary output. Data was abstracted for 48 publications (3196 patients) that met entry criteria. RESULTS: Higher resuscitation volumes compared to Parkland estimates were reported, but the trend of increasing resuscitation volumes over the last 30 years is not supported by regression of total fluid infused versus year of study. Mean 24h fluid infused for all studies was 5.2±1.1mL/kg per %TBSA. The mean 24h urinary output reported in 30 studies was 1.2±0.5mL/kg per hr. Burns with inhalation injuries (5 studies) received significantly more fluid than non-inhalation injured burn patients (5.0±1.3 versus 3.9±0.9mL/kg per %TBSA). Fluid infused and urinary outputs were similar for adults and pediatric patients. The most striking finding of our analyses was the great ranges of the means and high standard deviations of volumes infused compared to the original Baxter publication that introduced the Parkland formula CONCLUSIONS: These analyses suggest that burn units currently administer volumes larger than Parkland formula with great patient variability. Individual patient hourly data is needed to better understand the record of burn resuscitation and Fluid Creep.

Chemokine (C-X-C motif) receptor 4 regulates lung endothelial barrier permeability during resuscitation from hemorrhagic shock.

Chemokine (C-X-C motif) receptor 4 (CXCR4) agonists have been shown to protect lung endothelial barrier function in vitro. In vivo effects of CXCR4 modulation on lung endothelial permeability are unknown. Here we tested the effects of the CXCR4 agonist ubiquitin and the antagonist AMD3100 on lung vascular permeability and cytokine concentrations in a rat hemorrhage model. Animals were hemorrhaged (mean arterial blood pressure 30 mmHg for 30 min), treated with vehicle, ubiquitin (0.7 and 3.5 µmol/kg) or AMD3100 (3.5 µmol/kg), and resuscitated with crystalloids. Evans blue extravasation was employed to quantify lung vascular permeability. Ubiquitin dose-dependently reduced Evans blue extravasation into the lung. AMD3100 increased Evans blue extravasation. With AMD3100, TNFalpha levels in lung homogenates were increased; while TNFalpha levels were lower with ubiquitin, these differences did not reach statistical significance. Our findings suggest that CXCR4 regulates lung vascular permeability and further point towards CXCR4 as a drug target to confer lung protection during resuscitation from traumatic-hemorrhagic shock.