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.

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.

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.

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).

Sepsis - What's new in 2019?

PURPOSE OF REVIEW: Sepsis-3 guidelines have implications in a deeper understanding of the biopathology of the disease. Further, the review focuses on timely topics and new literature on fluid resuscitation, the value of steroids in sepsis, and new therapeutic options such as angiotensin II, vitamin C, and thiamine as well as the emerging role of procalcitonin (PCT) in managing antibiotics. RECENT FINDINGS: Traditional therapies such as type of crystalloid fluid administration and steroid therapy for sepsis are currently under re-evaluation. Angiotensin II is investigated for reversing vasodilatory shock. The role of capillary endothelium leak and cellular metabolism can be affected by vitamin C and thiamine levels. Biomarker level trends, specifically PCT, can aid clinical suspicion of infection. SUMMARY: Sepsis-3 shifts the focus from a noninfectious inflammatory process and an emphasis on a dysregulated host response to infection. Hyperchloremic crystalloid resuscitation is associated with poor clinical outcomes. Steroid administration can reverse shock physiology; however, mortality benefits remain uncertain. Angiotensin II, vitamin C, and thiamine are novel treatment options that need further validation. PCT assays can help discern between infectious and noninfectious inflammation.

Quality Improvement Project to Decrease Delivery Room Intubations in Preterm Infants.

BACKGROUND AND OBJECTIVES: Avoidance of delivery room intubation (DRI) reduces death or bronchopulmonary dysplasia (BPD) in preterm neonates. Our objective with this quality improvement project was to decrease DRI rates by improving face mask positive pressure ventilation (Fm-PPV) among infants born ≤29 weeks' gestation. METHODS: Key drivers of change were identified from a retrospective review of resuscitation records. A resuscitation bundle to optimize Fm-PPV including the use of a small round mask and end-tidal CO2 detectors, increasing peak inspiratory pressure when indicated, and debriefing after each intubation were implemented in consecutive plan-do-study-act cycles. The DRI rate was tracked by using a control chart. Resuscitation practice and outcomes of pre-quality improvement cohort (QIC) (January 2014-September 2015) were compared with post-QIC (October 2015-December 2016). RESULTS: Of the 314 infants who were resuscitated, 180 belonged to the pre-QIC and 134 to the post-QIC. The antenatal steroid administration rate was higher in the post-QIC (54% vs 88%). More infants in the post-QIC had resolution of bradycardia after Fm-PPV (56% vs 77%, P = .02). Infants in the post-QIC had lower DRI rates (58% vs 37%, P < .01), lower need for mechanical ventilation (85% vs 70%, P < .01), lower rates of BPD (26% vs 13%, P < .01), and severe retinopathy of prematurity (14% vs 5%, P = .01). Rates of DRI, BPD, and severe retinopathy of prematurity remained lower even after controlling for the potential confounders. CONCLUSIONS: Implementation of a resuscitation bundle decreased the DRI rate and improved outcomes of preterm infants.

The impact of prehospital administration of freeze-dried plasma on casualty outcome.

BACKGROUND: Hemorrhage is the most common preventable cause of death in both civilian and military trauma. There is no consensus regarding the appropriate fluid resuscitation protocol. Plasma, as a resuscitative fluid, has substantial benefits as a volume expander, owing to its relatively high oncotic pressure and its positive effect on trauma-induced coagulopathy by replenishing the lost coagulation factors, rather than diluting the casualty's remaining factors. The Israel Defense Force Medical Corps decided to use freeze-dried plasma (FDP) as the fluid of choice for casualties in hemorrhagic shock in the prehospital setting. The aim of our study is to compare the differences of coagulation, perfusion measurements, resource utilization, and outcome between casualties receiving FDP to casualties who did not receive FDP in the prehospital setting. METHODS: This is a retrospective matched cohort study based on two groups of casualties (those treated with FDP vs. those without FDP treatment). The control group was compiled in three steps of precision for age, sex, mechanism of injury and maximum level of severity for each nine injured body regions. Data were collected from the IDF Trauma Registry and The National Israel Trauma Registry. RESULTS: The study group comprised 48 casualties receiving FDP and 48 controls with no differences in demographic, evacuation time, and injury characteristics. The FDP group demonstrated a lower level of hemoglobin (12.7 gr/dzl) (odds ratio [OR], 3.11; 95% confidence interval [CI], 1.10-8.80), lower level of international normalized ratio (1.1) (OR, 3.09; 95% CI, 1.04-9.14), and lower level of platelets (230 × 109/L) (OR, 3.06; 95% CI, 1.16-8.06). No other differences were found between the two groups. CONCLUSION: The use of FDP in the prehospital setting has logistic benefits and a positive effect on coagulation profile, with no other significant effects. Future studies need to be performed on larger groups to verify trends or nullify our hypotheses. LEVEL OF EVIDENCE: Therapeutic, level IV.

Clinical Outcome of Epidural Hematoma Treated Surgically in the Era of Modern Resuscitation and Trauma Care.

OBJECTIVE: Patients from contemporary populations with traumatic brain injury (TBI) resulting from epidural hematoma (EDH) may differ regarding age, comorbidities, and coagulation status. We therefore analyzed predictors for the clinical outcome of patients with EDH treated surgically regarding modern approaches to resuscitation and trauma care. METHODS: A retrospective observational analysis was carried out. All patients included underwent surgery. The indication for surgery followed international guidelines. Retrospective data evaluation considered data reflecting the effectiveness of trauma care, baseline characteristics, and radiologic findings. In this analysis, we divided patients into 2 groups (isolated EDH vs. EDH plus other intracranial traumatic injuries). The neurologic outcome was assessed at discharge using the Glasgow Outcome Scale. RESULTS: Two hundred and sixty-eight patients with epidural hematoma, of whom 131 underwent surgery, were treated between January 1997 and December 2012 in our level-1 trauma center. The overall mortality was 6.8% (mortality for patients with Glasgow Outcome Scale score <9, 15%). As expected, factors with a highly significant (P < 0.01) impact on outcome were concomitant with other intracranial injuries, brain midline shift, and higher Injury Severity Score. Alcohol intoxication was a significant (P < 0.05) predictor of an unfavorable outcome. Anticoagulants and Glasgow Coma Scale score at admission had no significant impact on the outcome. CONCLUSIONS: The outcome for EDH is more favorable than decades ago, most probably reflecting a well-established chain of trauma care. Therefore, EDH is a treatable disease with a high probability of a favorable outcome.

Damage Control Resuscitation.

Damage control surgery is a combination of temporizing surgical interventions to arrest hemorrhage and control infectious source, with goal directed resuscitation to restore normal physiology. The convention of damage control surgery largely arose following the discovery of the lethal triad of hypothermia, acidosis, and coagulopathy, with the goal of Damage Control Surgery (DCS) is to avoid the initiation of this "bloody vicious cycle" or to reverse its progression. While hypothermia and acidosis are generally corrected with resuscitation, coagulopathy remains a challenging aspect of DCS, and is exacerbated by excessive crystalloid administration. This chapter focuses on resuscitative principles in the four settings of trauma care: the prehospital setting, emergency department, operating room, and intensive care unit including historical perspectives, resuscitative methods, controversies, and future directions. Each setting provides unique challenges with specific goals of care.

Abnormal Calcium Levels During Trauma Resuscitation Are Associated With Increased Mortality, Increased Blood Product Use, and Greater Hospital Resource Consumption: A Pilot Investigation.

BACKGROUND: Admission hypocalcemia predicts both massive transfusion and mortality in severely injured patients. However, the effect of calcium derangements during resuscitation remains unexplored. We hypothesize that any hypocalcemia or hypercalcemia (either primary or from overcorrection) in the first 24 hours after severe injury is associated with increased mortality. METHODS: All patients at our institution with massive transfusion protocol activation from January 2013 through December 2014 were identified. Patients transferred from another hospital, those not transfused, those with no ionized calcium (Ca) measured, and those who expired in the trauma bay were excluded. Hypocalcemia and hypercalcemia were defined as any level outside the normal range of Ca at our institution (1-1.25 mmol/L). Receiver operator curve analysis was also used to further examine significant thresholds for both hypocalcemia and hypercalcemia. Hospital mortality was compared between groups. Secondary outcomes included advanced cardiovascular life support, damage control surgery, ventilator days, and intensive care unit days. RESULTS: The massive transfusion protocol was activated for 77 patients of whom 36 were excluded leaving 41 for analysis. Hypocalcemia occurred in 35 (85%) patients and hypercalcemia occurred in 9 (22%). Mortality was no different in hypocalcemia versus no hypocalcemia (29% vs 0%; P = .13) but was greater in hypercalcemia versus no hypercalcemia (78% vs 9%; P < .01). Receiver operator curve analysis identified inflection points in mortality outside a Ca range of 0.84 to 1.30 mmol/L. Using these extreme values, 15 (37%) had hypocalcemia with a 60% mortality (vs 4%; P < .01) and 9 (22%) had hypercalcemia with a 78% mortality (vs 9%; P < .01). Patients with extreme hypocalcemia and hypercalcemia also received more red blood cells, plasma, platelets, and calcium repletion. CONCLUSIONS: Hypocalcemia and hypercalcemia occur commonly during the initial resuscitation of severely injured patients. Mild hypocalcemia may be tolerable, but more extreme hypocalcemia and any hypercalcemia should be avoided. Further assessment to define best practice for calcium management during resuscitation is warranted.

Damage control resuscitation: lessons learned.

BACKGROUND: Damage control resuscitation describes an approach to the early care of very seriously injured patients. The aim is to keep the patient alive whilst avoiding interventions and situations that risk worsening their situation by driving the lethal triad of hypothermia, coagulopathy and acidosis or excessively stimulating the immune-inflammatory system. It is critical that the concepts and practicalities of this approach are understood by all those involved in the early management of trauma patients. This review aims to summarise this and discusses current knowledge on the subject. INTERVENTIONS: Damage control resuscitation forms part of an overall approach to patient care rather than a specific intervention and has evolved from damage control surgery. It is characterised by early blood product administration, haemorrhage arrest and restoration of blood volume aiming to rapidly restore physiologic stability. The infusion of large volumes of crystalloid is no longer appropriate, instead the aim is to replace lost blood and avoid dilution and coagulopathy. In specific situations, permissive hypotension may also be of benefit, particularly in patients with severe haemorrhage from an arterial source. As rapid arrest of haemorrhage is so important, team-based protocols that deliver patients rapidly but safely, via CT scan where appropriate, to operating theatres or interventional radiology suites form a critical part of this process. CONCLUSIONS: Given that interventions are so time dependent in the severely injured, it is likely that by further improving trauma systems and protocols, improvements in outcome can still be made. Further research work in this area will allow us to target these approaches more accurately to those patients who can benefit most.