Tissue Hypoperfusion Research Articles

A retrospective study from a single center of 252 patients who underwent elective pancreaticoduodenectomy to compare perioperative hemodynamic optimization therapy and usual protocols in terms of perioperative cardiac function.

Perioperative hemodynamic optimization therapy is used to improve cardiac function to meet the increased demand during the perioperative period and to reduce hypervolemia or hypovolemia, tissue hypoperfusion and other postoperative complications. The present single center retrospective study aimed to compare perioperative hemodynamic optimization therapy and usual protocols in terms of perioperative cardiac function in 252 patients who underwent elective pancreaticoduodenectomy. Patients underwent elective pancreaticoduodenectomy under usual protocols of enhanced recovery after surgery procedures without intraoperative fluid optimization (UC; n=142) or with intraoperative fluid optimization (FO; n=110). For intraoperative fluid and vasoactive medication optimization, the patients of the UG cohort underwent usual cardiovascular monitoring and in the FO cohort, fluid interventions were given if stroke volume variations were >20% during and at the end of surgeries. The length of the hospital stay (discharge from operation theater to discharge from the ward) of the FO cohort was shorter than that of the UC cohort (11.02±2.07 days vs. 14.95±3.97 days; P<0.0001). The fluid balance (total input fluid-total output fluid) was higher in the UC cohort than that in the FO cohort (6,101±695 ml vs. 4,623±358 ml; P<0.0001). The number of patients that required intraoperatively metaraminol was greater in the UC cohort than in the FO cohort (P<0.0001). The number of patients that required intraoperatively noradrenaline (P<0.0001) and dopamine/dobutamine (P<0.0001) administration was greater in the FO cohort than those in the UC cohort. A greater number of patients in the UC cohort suffered from pancreatic fistula, arrhythmia, postoperative delirium, electrolyte disturbances, hyponatremia, refractory analgesia and required intraoperative blood products (P<0.05 vs. FO cohort). Pancreaticoduodenectomy under usual protocol with intraoperative fluid optimization may have perioperative and postoperative benefits (level of evidence, 3; technical efficacy stage, 1).

Echocardiographic indicators of fluid responsiveness in hospitalized dogs with compromised hemodynamics and tissue hypoperfusion.

To evaluate the accuracy of selected echocardiographic variables used to predict fluid responsiveness in hospitalized dogs with compromised hemodynamics and tissue hypoperfusion. Diagnostic test study in a prospective cohort of hospitalized dogs. Veterinary referral clinics. Forty-four hospitalized dogs with compromised hemodynamics and tissue hypoperfusion were utilized in this study. Echocardiographic examination before and after fluid replacement with 30ml/kg of lactated Ringer's solution. Pre-fluid replacement measurements of velocity of transmitral E wave (E-peak), the left ventricular end-diastolic internal diameter normalized to body weight (LVIDdN), and the left ventricular end-systolic internal diameter normalized to body weight (LVIDsN) were significantly lower in fluid-responsive patients compared with nonresponders (P<0.001). The area under the receiver operating characteristic curve (AUROC) with its 95% confidence interval (CI) for each significant predictor was as follows: E-peak 0.907 (0.776-1.000, P<0.001) and LVIDdN 0.919 (0.801-1.000, P<0.001). The predictive capacity of LVIDsN was not significantly better than chance (AUROC, 0.753; 95% CI, 0.472-1.000, P=0.078). A significant negative linear correlation was observed between the percentage of increase in velocity-time integral after expansion and the echocardiographic variables LVIDdN (rs =-0.452, P =0.023) and E-peak (rs =-0.396, P=0.008) pre-fluid replacement. The intraobserver and interobserver variability was very low(<5 %) for all measurements. In this study using critically ill dogs with compromised hemodynamics and tissue hypoperfusion, pre-fluid replacement measurements of LVIDdN and E-peak adequately predict fluid responsiveness. Because a small number of fluid nonresponders were involved in the present study (11.4%), further studies that include larger numbers of fluid-nonresponsive animals are required.

Effects of norepinephrine infusion during cardiopulmonary bypass on perioperative changes in lactic acid level (Norcal).

Hyperlactatemia, a problem reported in up to 30% of cardiac surgery patients, results from excessive production of or decreased clearance of lactate. It is typically a symptom of tissue hypoperfusion and may be associated with the prevalence of postoperative acute mesenteric ischemia and renal failure, or prolonged intensive care unit (ICU) and hospital stay, and increased 30-day mortality. Eighty cardiac surgery patients using cardiopulmonary bypass (CPB) were randomly assigned into either a placebo (n = 39) or norepinephrine 0.05-0.2 µg/kg/min (n = 41) as well as norepinephrine boluses during CPB to maintain mean arterial blood pressure (MAP) at 65 to 80 mm Hg. Patient assignments were done after receiving ethical approval to proceed. The primary result was the perioperative changes in lactic acid level. Secondary findings were also recorded, including hemodynamic variables, the incidence of vasoplegia, intraoperative hypotension, myocardial ischemia, the need for vasopressor support, postoperative complications, and mortality. The peak levels and perioperative changes in blood lactate during the first 24 postoperative hours, the number of patients who experienced early hyperlactatemia on admission to the ICU (Placebo: 46.2%, Norepinephrine: 51.2%, p = .650), vasoplegia, hemodynamic changes, incidences of intraoperative hypotension, myocardial ischemia, postoperative complications, and mortality rates were similar in the two groups. Patients in the norepinephrine group received lower intraoperative rescue norepinephrine boluses to maintain the target MAP (p = .039) and had higher MAP values during the CPB and intraoperative blood loss [mean difference [95% confidence interval]; 177 [20.9-334.3] ml, p = .027]. norepinephrine and placebo infusions during the CPB with the maintenance of MAP from 65 to 80 mmHg had comparative effects on the changes in blood lactate and incidence of vasoplegia after cardiac surgery. Norepinephrine infusion maintained higher MAP values during the CPB.

Renin as a Marker of Tissue Perfusion, Septic Shock and Mortality in Septic Patients: A Prospective Observational Study.

Sepsis is a life-threatening organ dysfunction caused by the dysregulation of the host’s response to an infection, where the dominant mechanism is tissue hypoperfusion. Currently, the marker used to define tissue disorders is lactate levels, which may be elevated in other disease states as well. Renin is an essential hormone for the proper functioning of the renin-angiotensin-aldosterone (RASS) system. It is secreted in the glomerular apparatus in response to hypoperfusion. This study aimed to assess the usefulness of renin as a marker of tissue hypoperfusion in patients with sepsis and septic shock. A final group of 48 patients treated for sepsis and septic shock in the intensive care unit was included. Blood samples for renin quantification were collected in the morning as a part of routine blood analysis on the first, third, and fifth days. Sepsis was diagnosed in 19 patients (39.6%), and septic shock was diagnosed in 29 patients (60.4%). There was no significant difference in renin concentration between patients who received and did not receive continuous renal replacement therapy (CRRT) on any study day. Therefore, all samples were analyzed together in subsequent analyses. There was a significant difference in renin concentration between sepsis survivors and non-survivors on the third (31.5 and 119.9 pg/mL, respectively) and fifth (18.2 and 106.7 pg/mL, respectively) days. As a survival marker, renin was characterized by 69% and 71% overall accuracy if determined on the third and fifth days, respectively. There was a significant difference in renin concentration between sepsis and septic shock patients on the first (45.8 and 103.4 pg/mL, respectively) and third (24.7 and 102.1 pg/mL, respectively) days. At an optimal cut-off of 87 pg/mL, renin had very good specificity and a positive likelihood ratio. Renin was a strong predictor of mortality in patients with sepsis and septic shock. Further, the level of renin in patients with septic shock was significantly higher than in patients with sepsis. In combination with the assessment of lactate concentration, renin seems to be the optimal parameter for monitoring tissue hypoperfusion and could be helpful for septic shock diagnosis, as well as for identifying candidate patients for CRRT.

How can assessing hemodynamics help to assess volume status?

In critically ill patients, fluid infusion is aimed at increasing cardiac output and tissue perfusion. However, it may contribute to fluid overload which may be harmful. Thus, volume status, risks and potential efficacy of fluid administration and/or removal should be carefully evaluated, and monitoring techniques help for this purpose. Central venous pressure is a marker of right ventricular preload. Very low values indicate hypovolemia, while extremely high values suggest fluid harmfulness. The pulmonary artery catheter enables a comprehensive assessment of the hemodynamic profile and is particularly useful for indicating the risk of pulmonary oedema through the pulmonary artery occlusion pressure. Besides cardiac output and preload, transpulmonary thermodilution measures extravascular lung water, which reflects the extent of lung flooding and assesses the risk of fluid infusion. Echocardiography estimates the volume status through intravascular volumes and pressures. Finally, lung ultrasound estimates lung edema. Guided by these variables, the decision to infuse fluid should first consider specific triggers, such as signs of tissue hypoperfusion. Second, benefits and risks of fluid infusion should be weighted. Thereafter, fluid responsiveness should be assessed. Monitoring techniques help for this purpose, especially by providing real time and precise measurements of cardiac output. When decided, fluid resuscitation should be performed through fluid challenges, the effects of which should be assessed through critical endpoints including cardiac output. This comprehensive evaluation of the risk, benefits and efficacy of fluid infusion helps to individualize fluid management, which should be preferred over a fixed restrictive or liberal strategy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00134-022-06808-9.

Intestinal Injury in Ugandan Children Hospitalized With Malaria.

Severe malaria is associated with multiple organ dysfunction syndrome (MODS), which may involve the gastrointestinal tract. In a prospective cohort study in Uganda, we measured markers of intestinal injury (intestinal fatty-acid binding protein [I-FABP] and zonula occludens-1 [ZO-1]) and microbial translocation (lipopolysaccharide binding protein [LBP] and soluble complement of differentiation 14 [sCD14]) among children admitted with malaria. We examined their association with biomarkers of inflammation, endothelial activation, clinical signs of hypoperfusion, organ injury, and mortality. We enrolled 523 children (median age 1.5 years, 46% female, 7.5% mortality). Intestinal FABP was above the normal range (≥400 pg/mL) in 415 of 523 patients (79%). Intestinal FABP correlated with ZO-1 (ρ = 0.11, P = .014), sCD14 (ρ = 0.12, P = .0046) as well as markers of inflammation and endothelial activation. Higher I-FABP levels were associated with lower systolic blood pressure (ρ = -0.14, P = .0015), delayed capillary refill time (ρ = 0.17, P = .00011), higher lactate level (ρ = 0.40, P < .0001), increasing stage of acute kidney injury (ρ = 0.20, P = .0034), and coma (P < .0001). Admission I-FABP levels ≥5.6 ng/mL were associated with a 7.4-fold higher relative risk of in-hospital death (95% confidence interval, 1.4-11, P = .0016). Intestinal injury occurs commonly in children hospitalized with malaria and is associated with microbial translocation, systemic inflammation, tissue hypoperfusion, MODS, and fatal outcome.

Turn Up the HETE on Septic Shock.

Septic shock is life-threatening organ dysfunction due to a dysregulated response to infection. It is a leading cause of death caused by the excessive release of cytokines and inflammatory mediators in response to bacterial endotoxins. It produces hypotension refractory to vasoconstrictors leading to tissue hypoperfusion and multiple organ failure. Despite intensive investigation, there still are no specific pharmacologic treatments. Current therapy relies on supportive care, including antibiotics, fluid resuscitation, corticosteroids, and pressor agents. This commentary summarizes little-known previous observations that inhibition of vascular 20-hydroxyeicosatetraenoic acid (20-HETE) by nitric oxide plays a key role in sepsis. It also highlights the new and exciting current report by Tunctan et al (2022) in this issue of Journal of Cardiovascular Pharmacology that administration of a 20-HETE mimetic can prevent lipopolysaccharide-induced vascular hyporeactivity, hypotension, and tachycardia in rats by activating the recently discovered GPR75/20-HETE receptor. Overall, these results provide a compelling case for initiating 20-HETE clinical trials to prevent hypotension, multiple organ failure, and death in septic shock.

Fluid overload as a predictor of morbidity and mortality in pediatric patients following congenital heart surgery.

Patients undergoing congenital heart surgery with cardiopulmonary bypass frequently require the administration of intravenous fluids and blood products due to hemodynamic instability. Correctly performed fluid resuscitation can revert the state of tissue hypoperfusion in the different organs. However, excessive fluid administration and acute kidney injury may promote fluid overload (FO) and increase the risk of complications, hospital stay, and mortality. We conducted a prospective longitudinal study of pediatric patients with congenital heart surgery and cardiopulmonary bypass in the Pediatric Cardiac Intensive Care Unit (PCICU), Instituto Nacional de Pediatría, from July 2018 to December 2019. Fluid overload was quantified every 24 hours during the first 3 days of stay at the PCICU and expressed as a percentage. We recorded PCICU stay, days of mechanical ventilation, and mortality as outcome variables. We included 130 patients. The main factors associated with fluid overload were age < 1 year (p < 0.001), weight < 5 kg (p < 0.001), and longer cardiopulmonary bypass time (p = 0.003). Patients with fluid overload ≥ 5% had higher inotropic score (p < 0.001), higher oxygenation index (p < 0.001), and longer mechanical ventilation time (p < 0.001). Fluid overload ≥ 5% was associated with higher postoperative mortality (odds ratio 89, p = 0.004). Fluid overload can be used as a prognostic factor in the evolution of pediatric patients undergoing congenital heart surgery since it is associated with increased morbidity and mortality.

Peripheral tissue hypoperfusion predicts post intubation hemodynamic instability

BackgroundTracheal intubation and invasive mechanical ventilation initiation is a procedure at high risk for arterial hypotension in intensive care unit. However, little is known about the relationship between pre-existing peripheral microvascular alteration and post-intubation hemodynamic instability (PIHI).MethodsProspective observational monocenter study conducted in an 18-bed medical ICU. Consecutive patients requiring tracheal intubation were eligible for the study. Global hemodynamic parameters (blood pressure, heart rate, cardiac function) and tissue perfusion parameters (arterial lactate, mottling score, capillary refill time [CRT], toe-to-room gradient temperature) were recorded before, 5 min and 2 h after tracheal intubation (TI). Post intubation hemodynamic instability (PIHI) was defined as any hemodynamic event requiring therapeutic intervention.ResultsDuring 1 year, 120 patients were included, mainly male (59%) with a median age of 68 [57–77]. The median SOFA score and SAPS II were 6 [4–9] and 47 [37–63], respectively. The main indications for tracheal intubation were hypoxemia (51%), hypercapnia (13%), and coma (29%). In addition, 48% of patients had sepsis and 16% septic shock. Fifty-one (42%) patients develop PIHI. Univariate analysis identified several baseline factors associated with PIHI, including norepinephrine prior to TI, sepsis, tachycardia, fever, higher SOFA and high SAPSII score, mottling score ≥ 3, high lactate level and prolonged knee CRT. By contrast, mean arterial pressure, baseline cardiac index, and ejection fraction were not different between PIHI and No-PIHI groups. After adjustment on potential confounders, the mottling score was associated with a higher risk for PIHI (adjusted OR: 1.84 [1.21–2.82] per 1 point increased; p = 0.005). Among both global haemodynamics and tissue perfusion parameters, baseline mottling score was the best predictor of PIHI (AUC: 0.72 (CI 95% [0.62–0.81]).ConclusionsIn non-selected critically ill patients requiring invasive mechanical ventilation, tissue hypoperfusion parameters, especially the mottling score, could be helpful to predict PIHI.

Update on vitamin C administration in critical illness.

Several studies have recently explored the effects of intravenous vitamin C in sepsis. We aimed to summarize their findings to provide perspectives for future research. Sepsis trials examined 6 g/day of intravenous vitamin C with or without the thiamine and/or hydrocortisone compared with placebo or hydrocortisone. Network meta-analysis reported that intravenous vitamin C, thiamine, hydrocortisone, or combinations of these drugs was not proven to reduce long-term mortality. However, the component network meta-analysis suggested an association of high-dose (>6 g/day) and very-high dose vitamin C (>12 g/day) and decreased mortality but with low certainty. The preclinical investigations have, however, advanced to much higher doses of intravenous vitamin C therapy since a scoping review on harm reported that mega-doses of intravenous vitamin C (50-100 g/day) had been administered without any conclusive adverse effects. In a Gram-negative sheep model, renal tissue hypoperfusion was reversed, followed by improvements in kidney function when a mega-dose of vitamin C (150 g/day equivalent) was administered. The effect of intravenous vitamin C in critically ill patients has yet to be determined and might be dose-dependent. Clinical studies of very high or mega doses of vitamin C are justified by preclinical data.

54-Year-Old Woman With Altered Mental Status and Abdominal Pain

54-Year-Old Woman With Altered Mental Status and Abdominal Pain

The use of inotropes and not hyperchloremia is an independent risk factor for acute kidney injury during the postoperative period of cardiac surgery. A prospective cohort-study

IntroductionAcute kidney injury (AKI) is a marker of poor prognostic after cardiac surgery. Recent studies suggest that hyperchloraemia may be significantly associated with the development of this complication. However, there is little information regarding the prevalence of abnormal chloride concentrations after cardiac surgery and its relationship to postoperative AKI. On the other hand, the use of inotropes in postoperative cardiac surgery patients has been associated with several types of adverse outcomes. AimsDetermine the relationship between hyperchloraemia and AKI in patients following cardiac surgery and to evaluate whether variables associated with tissue hypoperfusion or the use of inotropes are related to the development of this complication. MethodsAn observational cohort study was performed at a hospital with a focus on high-complexity cardiovascular patients. We included 464 adult patients who had undergone heart surgery. ResultsAKI was found in 12.7% of the patients. Additionally, 76% had had hyperchloraemia at least once during the first 48 h after surgery. The highest serum chloride level recorded postoperatively was significantly higher in the patients with AKI. However, when the results were adjusted for covariables, the association was not significant. In the assessment of secondary outcomes, the analysis identified a significant association between AKI and arterial lactate levels on admission to the intensive care unit, but the most notable association was between AKI and the use of inotropes. ConclusionsPostoperative hyperchloraemia is common but is not independently associated with AKI. This complication is mainly related to tissue hypoperfusion or the need for postoperative inotrope use.

Expression of interleukin 1, interleukin 27, and TNF α genes in patients with ischemic cardiomyopathy versus idiopathic dilated cardiomyopathy: A case-control study.

Background and AimsCongestive heart failure is a complex multifactorial syndrome due to tissue hypoperfusion that is affected by some factors like inflammatory cytokines. In our study, we investigated the exact gene expression of three inflammatory cytokines in ischemic and idiopathic cardiomyopathy patients.MethodsFrom 49 studied recipients in the ischemic group, 23 (46.9%) were male and from 40 studied recipients in the idiopathic dilated cardiomyopathy group, 19 (47.5%) were male. For the quantitative analysis of interleukin (IL)‐1, IL‐27, and tumor necrosis factor (TNF)‐α messenger RNAs expression level, the SYBR Green real‐time polymerase chain reaction method was performed using SYBRPremix Ex TaqTM II (Tli RNaseH Plus; Takara) and designed primers specific for each gene in an iQ5 thermocycler (BioRad Laboratories) according to the manufacturer's instructions.ResultsOur results showed that the expression level of IL‐1 and TNF‐α were significantly higher in the ischemic patients compared to healthy controls (p < 0.001, p < 0.01, respectively); also, we found higher levels of IL‐1 and IL‐27 gene expressions in idiopathic patients compared to healthy controls (p < 0.001, p < 0.001, respectively). There were not any significant differences in IL‐1, IL‐27, and TNF‐α expression levels between ischemic patients and idiopathic ones.ConclusionAlthough we would introduce IL‐1, IL‐27, and TNF‐α as effective inflammatory cytokines on myocardial functions in ischemic and idiopathic cardiomyopathy patients, there is not any difference between these two groups in gene expression of three main inflammatory cytokines.

Treatment of Hyperlactatemia in Acute Circulatory Failure Based on CO2-O2-Derived Indices: Study Protocol for a Prospective, Multicentric, Single, Blind, Randomized, Superiority Study (The LACTEL Study).

BackgroundHyperlactatemia is a biological marker of tissue hypoperfusion with well-known diagnostic, prognostic, and therapeutic implications in shock states. In daily clinical practice, it is difficult to find out the exact mechanism underlying hyperlactatemia. Central venous to arterial CO2 difference (pCO2 gap) is a better parameter of tissue hypoperfusion than the usual ones (clinical examination and mixed venous saturation). Furthermore, the ratio between the pCO2 gap and p(v–a)CO2/C(a–v)O2 may be a promising indicator of anaerobic metabolism, allowing for the identification of different causes of tissue hypoxia and hyperlactatemia. The main aim of the study is to demonstrate that initial hemodynamic resuscitation based on an algorithm integrating the pCO2 gap and p(v–a)CO2/C(a–v)O2 ratio vs. usual clinical practice in acute circulatory failure improves lactate clearance.MethodsLACTEL is a randomized, prospective, multicentric, controlled study. It compares the treatment of hyperlactatemia using an algorithm based on the pCO2 gap and P(v–a)CO2/C(a–v)O2 ratio vs. usual clinical practice in acute circulatory failure. A total of 90 patients were enrolled in each treatment group. The primary endpoint is the number of patients with a lactate clearance of more than 10% 2 h after inclusion. Lactate levels were monitored during the first 48 h of treatment as hemodynamic parameters, biological markers of organ failure, and 28-day mortality.DiscussionpCO2 derivate indices may be of better interest than routine clinical indices to differentiate causes of hyperlactatemia and diagnose anaerobiosis. LACTEL results will provide clinical insights into the role of these indices in the early hemodynamic management of acute circulatory failure in the ICU.Clinical Trial Registrationwww.clinicaltrials.gov; identifier: NCT05032521.

Effects of ischemic conditioning on head and neck free flap oxygenation: a randomized controlled trial

Flap failure after microvascular reconstructive surgery is a rare but devastating complication caused by reperfusion injury and tissue hypoperfusion. Remote ischemic conditioning (RIC) provides protection against ischemia/reperfusion injury and reduces tissue infarction. We hypothesized that RIC would enhance flap oxygenation and exert organ-protective effects during head and neck free flap reconstructive surgery. Adult patients undergoing free flap transfer surgery for head and neck cancer were randomized to receive either RIC or sham-RIC during surgery. RIC consisted of four cycles of 5-min ischemia and 5-min reperfusion applied to the upper or lower extremity. The primary endpoint, tissue oxygen saturation of the flap, was measured by near-infrared spectroscopy on the first postoperative day. Organ-protective effects of RIC were evaluated with infarct size of rat hearts perfused with plasma dialysate from patients received RIC or sham-RIC. Between April 2018 and July 2019, 50 patients were randomized (each n = 25) and 46 were analyzed in the RIC (n = 23) or sham-RIC (n = 23) groups. Tissue oxygen saturation of the flap was similar between the groups (85 ± 12% vs 83 ± 9% in the RIC vs sham-RIC groups; P = 0.471). Myocardial infarct size after treatment of plasma dialysate was significantly reduced in the RIC group (44 ± 7% to 26 ± 6%; P = 0.018) compared to the sham-RIC group (42 ± 6% to 37 ± 7%; P = 0.388). RIC did not improve tissue oxygenation of the transferred free flap in head and neck cancer reconstructive surgery. However, there was evidence of organ-protective effects of RIC in experimental models.Trial registration: Registry number of ClinicalTrials.gov: NCT03474952.

Septic Shock

Patients who present to the emergency department demonstrating clinical signs of circulatory shock constitute a medical emergency, often associated with significant mortality. Severe sepsis, characterized as infection with systemic manifestations and accompanying organ dysfunction or tissue hypoperfusion, can lead to septic shock. Septic shock is defined as severe sepsis plus sepsis-induced hypotension not reversed with adequate fluid resuscitation. Hypotension may be defined by a drop in systolic blood pressure (SBP) to &lt; 90 mm Hg or by at least a 40-mm Hg from baseline. The inadequate perfusion of critical organs (heart, liver, and kidneys) may lead to significant morbidity and mortality.

Esophageal perforation due to acute esophageal necrosis: A case report and a comprehensive literature review

Background. Acute esophageal necrosis is a rare and potentially lethal entity. The pathogenesis is multifactorial, generally presenting with symptoms of upper gastrointestinal bleeding. We present a case that presents atypically with initial esophageal perforation. Case presentation. A 46-year-old man with a history of alcoholism and cocaine use, an active smoker, and a ruptured celiac trunk aneurysm treated by embolization, who, after acute chest and epigastric pain, is diagnosed with a Stanford B thoracoabdominal aortic dissection, being repaired endovascularly by placing an aortic endoprosthesis. Due to clinical suspicion of mesenteric ischemia complicated with esophageal/gastric perforation, a postoperative tomography was performed, revealing perforation of the esophagus distal to the left pleura and ischemic cholecystitis. Transhiatal esophagectomy, cervical esophagostomy, Witzel-type decompressive gastrostomy, Witzel-type feeding jejunostomy, classic cholecystectomy, and mediastinum drainage were performed. During the postoperative period, the patient remained in critical condition, dying as a result of hypoxic encephalopathy. The histopathological study reported acute transmural esophageal ischemia. Discussion. Tissue hypoperfusion plays a dominant role in the pathogenesis of acute esophageal necrosis. Esophageal perforation is a serious complication and can occur in the early stages, with esophagectomy and deferred digestive reconstruction being the appropriate treatment. Conclusion. Ischemia is a fundamental mechanism of acute esophageal necrosis; its diagnosis must always be established in the various complications that may occur in patients with hemodynamic compromise, in order to obtain a timely treatment.

Advances in Neuroimaging and Monitoring to Defend Cerebral Perfusion in Noncardiac Surgery.

Noncardiac surgery conveys a substantial risk of secondary organ dysfunction and injury. Neurocognitive dysfunction and covert stroke are emerging as major forms of perioperative organ dysfunction, but a better understanding of perioperative neurobiology is required to identify effective treatment strategies. The likelihood and severity of perioperative brain injury may be increased by intraoperative hemodynamic dysfunction, tissue hypoperfusion, and a failure to recognize complications early in their development. Advances in neuroimaging and monitoring techniques, including optical, sonographic, and magnetic resonance, have progressed beyond structural imaging and now enable noninvasive assessment of cerebral perfusion, vascular reserve, metabolism, and neurologic function at the bedside. Translation of these imaging methods into the perioperative setting has highlighted several potential avenues to optimize tissue perfusion and deliver neuroprotection. This review introduces the methods, metrics, and evidence underlying emerging optical and magnetic resonance neuroimaging methods and discusses their potential experimental and clinical utility in the setting of noncardiac surgery.

MO281: Development of an Experimental Model of Haemodynamic Frailty Predisposing to Acute Kidney Injury

Abstract BACKGROUND AND AIMS Frailty is a pre-morbid condition characterized by physiological decline and reduced physiological reserve leading to increased vulnerability to disease, especially common among older adults. Tissue and organ function is underpinned by effective haemodynamic regulation coping with everyday acute challenges and stressors. Impairment of the haemodynamic response may lead to tissue hypoperfusion and subsequent adverse events, such as acute kidney injury (AKI) and others. ‘Haemodynamic frailty’ defines a clinically silent condition characterized by a compromised haemodynamic reserve and impaired adaptive response to supervening circumstances (i.e. stressors such as drugs). Yet, frailty also offers a window of opportunity for disease prevention and health maintenance. Dehydration, hypertension and some drugs are important causes of haemodynamic frailty [1]. In this work, we aimed to develop a pre-clinical model of haemodynamic frailty, based on dehydration and hypertension, predisposing to AKI. METHOD Three-month old male spontaneously hypertensive (SHR) rats were divided into four groups: (1) Control (CT): rats with ad libitum access to drinking water, receiving saline solution (0.9% NaCl, i.p.). (2) Cisplatin (CDDP): rats with ad libitum access to drinking water, receiving a sub nephrotoxic dose of cisplatin (2.5 mg/kg, i.p.). (3) Water deprivation (WD): rats with no access to drinking water during 48 h, receiving saline solution (0.9% NaCl, i.p.). (4) Water deprivation + cisplatin (WD + CDDP): rats with no access to drinking water during the 48 h previous to the cisplatin administration (2.5 mg/kg, i.p.). The dose of cisplatin had proved to be sub-nephrotoxic for normal rats in our previous studies [2]. 24-hour urine and tail vein blood samples were collected at basal state (B), 2 days after water deprivation (D0), and 4 days after cisplatin administration (D4, day of maximum kidney damage). Urine samples were analysed for volume (urinary flow), specific gravity, osmolality, and proteinuria (Bradford method). Haematocrit was calculated from blood samples and plasma was used to determine osmolality, concentration of creatinine (Jaffe reaction) and urea (Jung method). RESULTS SHR rats with 48 hours of water deprivation showed a 10% weight loss, increases in haematocrit and plasma osmolality and a highly concentrated urine (with elevated levels of urine specific gravity and osmolality), which indicates a moderate to severe state of dehydration. No alterations in renal function were observed after water deprivation. Administration of cisplatin triggered significant increases in plasma creatinine, plasma urea and proteinuria, indicative of AKI, only in rats previously deprived of water for 48 h. All the parameters studied remained normal in cisplatin-treated rats without water restriction. Our results suggest that our experimental animal model, based on a combination of hypertension and dehydration, reproduces a state of haemodynamic frailty in which rats become predisposed to undergoing renal failure following exposure to stressors (e.g. a sub-nephrotoxic dose of cisplatin) that are harmless to haemodynamically competent rats. CONCLUSION To our knowledge, this is the first experimental model of haemodynamic frailty predisposing to AKI. This model will allow us to further study mechanisms and biomarkers useful for diagnosis and stratification of haemodynamic frailty in order to develop strategies to prevent undesired health outcomes, including renal damage.

Exacerbated Vascular Inflammation Following Traumatic Hemorrhage in Obese Rats

IntroductionObesity increases the risk for morbidity and mortality in trauma patients. These complications are associated with prolonged tissue hypoperfusion, hypercoagulability, and edema that reflect profound vascular damage. Traumatic hemorrhage acutely attenuates vascular responsiveness, but the degree of this dysfunction during the obese state is not known. Traumatic hemorrhage also increases circulating inflammatory cytokines; however, the local inflammatory response in vascular cells is unknown. We hypothesized that obesity potentiates trauma‐induced vascular inflammation and dysfunction.MethodsMale Sprague‐Dawley rats (~250g) fed either normal chow (NC; 13.5% kcal fat, n=20), moderate‐fat (MF; 33% kcal fat, n=20), or high‐fat (HF; 60% kcal fat, n=20) diet for 6‐8 weeks were assigned to a traumatic hemorrhage protocol or sham control. Under anesthesia, hemorrhage was induced by the laceration of a mesenteric artery and a Grade V splenic injury. Hypotension (mean arterial pressure = 30–40 mm Hg) was maintained for 30 minutes. Vasoconstrictor and vasodilator properties were assessed ex vivo in isolated mesenteric arteries pre‐ and post‐ hemorrhage. Carotid arteries collected after hemorrhage or sham control were flushed with trizol to collect endothelial cells (ECs). Gene expression was assessed in ECs and the remaining carotid artery (media + adventitia) cells for pro‐inflammatory interleukin (IL)‐1β, and IL‐6, pro‐oxidant NADPH oxidase 2 (NOX2), and α‐adrenergic receptor.ResultsIn NC rats, hemorrhage attenuated norepinephrine‐induced vasoconstriction and endothelium‐dependent dilation. This was accompanied by elevated IL‐1β expression in carotid artery ECs and elevated IL‐1β, IL‐6, NOX2, and α‐adrenergic receptor expression in the carotid artery media + adventitia post‐hemorrhage versus sham control. In MF and HF rats, norepinephrine‐induced vasoconstriction and endothelium‐dependent dilation did not change pre‐ to post‐hemorrhage. In sham animals, endothelial cell IL‐1β and NOX2 expression were higher in HF compared with NC rats. Similar to NC rats, the MF and HF rats had higher IL‐1β expression in carotid artery ECs, and IL‐1β, IL‐6, NOX2, and α‐adrenergic receptor expression in the carotid artery media + adventitia post‐hemorrhage compared with sham. The hemorrhage‐induced elevation of IL‐1β in carotid artery ECs and media + adventitia was greater in HF rats compared with NC and MF rats.ConclusionOur clinically‐relevant model of traumatic hemorrhage attenuates vascular responsiveness and induces vascular inflammation. The attenuated vascular responsiveness following hemorrhage is absent in MF and HF rats, while the elevated vascular inflammation persists. HF rats have an amplified arterial inflammatory response to hemorrhage, both in ECs and in cells of the media + adventitia. The augmented vascular inflammatory response to hemorrhage in HF rats may explain the worse outcomes in obese trauma patients.