Treatment Of Hypovolemic Shock Research Articles

Гиповолемический шок у взрослых. Клинические рекомендации Общероссийской общественной организации «Федерация анестезиологов и реаниматологов»

The article presents the main provisions of clinical guidelines for the diagnosis and treatment of hypovolemic shock in adults, approved by the All-Russian public organization "Federation of Anesthesiologists and Resuscitators" in 2024. The relevance of the problem is associated with a significant prevalence and high mortality rates in hypovolemic shock. The recommendations include issues of etiology, pathogenesis, clinical picture, methods of laboratory and instrumental diagnostics of hypovolemic shock. The features of intensive care for hypovolemic shock are presented, including approaches to the administration of vasopressor and inotropic drugs, recommendations for the choice of infusion and adjuvant therapy, including the correction of coagulopathy in hemorrhagic shock. The issues of resuscitation damage control strategy are discussed. The criteria for the quality of medical care for adult patients with hypovolemic shock and algorithms for the doctor's actions in the diagnosis and intensive care of patients with hypovolemic shock are presented.

Levosimendan and Dobutamin Attenuate LPS-Induced Inflammation in Microglia by Inhibiting the NF-κB Pathway and NLRP3 Inflammasome Activation via Nrf2/HO-1 Signalling.

Hypovolemic shock is a circulatory failure, due to a loss in the effective circulating blood volume, that causes tissue hypoperfusion and hypoxia. This condition stimulates reactive oxygen species (ROS) and pro-inflammatory cytokine production in different organs and also in the central nervous system (CNS). Levosimendan, a cardioprotective inodilator, and dobutamine, a β1-adrenergic agonist, are commonly used for the treatment of hypovolemic shock, thanks to their anti-inflammatory and antioxidant effects. For this reason, we aimed at investigating levosimendan and dobutamine's neuroprotective effects in an "in vitro" model of lipopolysaccharide (LPS)-induced neuroinflammation. Human microglial cells (HMC3) were challenged with LPS (0.1 µg/mL) to induce an inflammatory phenotype and then treated with levosimendan (10 µM) or dobutamine (50 µM) for 24 h. Levosimendan and dobutamine significantly reduced the ROS levels and markedly increased Nrf2 and HO-1 protein expression in LPS-challenged cells. Levosimendan and dobutamine also decreased p-NF-κB expression and turned off the NLRP3 inflammasome together with its downstream signals, caspase-1 and IL-1β. Moreover, a reduction in TNF-α and IL-6 expression and an increase in IL-10 levels in LPS-stimulated HMC3 cells was observed following treatment. In conclusion, levosimendan and dobutamine attenuated LPS-induced neuroinflammation through NF-κB pathway inhibition and NLRP3 inflammasome activation via Nrf2/HO-1 signalling, suggesting that these drugs could represent a promising therapeutic approach for the treatment of neuroinflammation consequent to hypovolemic shock.

Alpha-gal syndrome: when treatment of hypovolemic shock can lead to anaphylaxis.

Delayed anaphylaxis after ingestion of red meat because of galactose-alpha-1,3-galactose (alpha-gal) syndrome has increased in recent years. The mechanism involves an immunoglobulin E reaction to alpha-gal, a molecule found in mammalian meat, dairy products, medications and excipients containing mammalian-derived components, and tick salivary glycans. Sensitization occurs due to the bite of a lone star tick and the transmission of alpha-gal molecules into person's bloodstream. We describe a case of alpha-gal syndrome with severe food, drug, and perioperative allergy in which anaphylaxis with hypovolemic shock occurred immediately after an emergency surgical procedure, when a gelatin-containing drug was injected. This case study confirms that the clinical manifestations of alpha-gal syndrome could be different depending on the route of administration, with immediate reactions if an alpha-gal-containing drug is injected and delayed type allergic manifestations occurring several hours after oral intake. The purpose of this report is to highlight the importance of risk communication in case of exposure to medical products and surgical procedures of patients with alpha-gal syndrome and to encourage drug manufacturers to indicate clearly the origin of excipients in product literature.

Alpha-gal syndrome and treatment of hypovolemic shock.

Alpha-gal syndrome and treatment of hypovolemic shock.

Abstract 118: Multicentric, Randomized Controlled Phase III Study of Centhaquine (Lyfaquin®) as an Effective First-in-class Resuscitative Agent in Hypovolemic Shock Patients

Background: Centhaquine (CQ) is a novel, first-in-class resuscitative agent for the treatment of hypovolemic shock. Methods: Efficacy of CQ for the treatment of hypovolemic shock as an adjuvant to standard of care (SOC) was evaluated in a prospective, multi-center, randomized, double-blind, placebo-controlled Phase 3 study. Key inclusion criteria were; systolic blood pressure of <90 mm Hg, blood lactate levels of > 2 mmol/L and patients receiving SOC in a hospital or ICU setting. Patients were randomized in a 2:1 ratio either to the CQ group receiving CQ dose of 0.01 mg/kg by IV infusion along with SOC or to the control group receiving SOC plus saline. Primary endpoints of the study were change in systolic blood pressure (SBP) and diastolic blood pressure (DBP), change in blood lactate levels and change in base deficit. Mortality through day 28 was the key secondary endpoint. Results: A total of 197 patients were screened, of which 105 patients met the eligibility criteria and were included in the study. Out of 105 patients, 71 patients were randomized to CQ group and 34 patients to control group. Demographics and baseline characteristics of patients in both groups was comparable. Hemoglobin level was 9.38 ± 0.71 g/dL and 8.73 ± 0.55 g/dL in control and CQ groups, respectively at the time of inclusion in the study. At 24 hours of resuscitation, SBP of more than 110 mmHg was in 59.38% patients of control and 81.82% patients of CQ group (P=0.00842). Similarly, at 24 hours of resuscitation, DBP of more than 70 mmHg was in 50.00% patients in control group and 78.46% patients in CQ group (P=0.002175). The number of patients with blood lactate levels of 1.5 mmol/L or less were 46.88% in the group with standard treatment compared to 69.35% in CQ group (P=0.0168). The number of patients with base-deficit of less than minus 2 were 46.88% in standard treatment group compared to 68.25% in those receiving CQ (P=0.0217). CQ treatment significantly reduced the mortality rate. In the control group, the mortality rate was 11.76% compared to 2.94% in the CQ group (odds ratio: 4.4; 95% CI 0.9651 to 23.74 and P=0.037). No drug related adverse event was reported. Conclusion: Centhaquine (Lyfaquin®) is a highly efficacious resuscitative agent for the treatment of hypovolemic shock as an adjuvant to SOC.

Activated Factor Seven (aFVII) versus Aminocaproic Acid for Treatment of Traumatic Retro-Peritoneal Hematoma

Introduction: Off-labelled use of activated Factor VII (aFVII) in severe traumatic bleeding has been used as an alternative to aminocaproic. Aim of Work: The aim of this study is to compare the efficacy of aFVII with aminocaproic acid in the medical treatment of retroperitoneal bleeding, treatment of hypovolemic shock and preventing complications of massive blood transfusion. Materials and Methods: 80 patients with traumatic retro-peritoneal hematoma were allocated into two groups of 40 patients each. Patients in Group A received aminocaproic acid, while patients of group B received aFVII. The number of packed RBCs given to achieve the target Hb level and time to get to this target Hb level (>10 gm%) were recorded as indicators of control bleeding. Blood pressure, pulse, arterial blood gasses and urine output were recorded as indicators of successful treatment of hypovolemic shock. Hypoxic index, chest X-ray and coagulation profile were used as indicators for complications. Results: There was a significantly smaller number of packed RBCs given to patients of group B to achieve the target Hb level and this target Hb level was achieved in a shorter time. There was a significantly higher number of patients in group B compared to group A who had normal blood pressure, pulse and urine output, pH and bicarbonate concentration. There was a significantly smaller number of patients who developed DIC and TRALI in group B compared to group A. Conclusion: aFVII was more effective than aminocaproic acid and needed a shorter time to stop retroperitoneal bleeding, treat hypovolemic shock, restore adequate tissue perfusion and protect patients from complications of massive blood transfusion.

The Study on Dorsal Venous Arch of Upper Limb Among Nepalese Medical Students at Tertiary Level Teaching Institute

Introduction: Dorsal venous arch of upper limb is the beginning site for cephalic and basilic veins. The superficial veins are clinically important for venipuncture, blood collection and blood donation as well as for health screening and testing, intravenous transfusion for the emergency treatment of hypovolemic shock. Veins of the upper limb are also used for total parental nutrition, therapeutic invasive procedure and blood samples. The Dorsal Venous Arch is superficially placed and can be easily made prominent by putting a tourniquet at the wrist for any such surgical and therapeutic purposes.
 Methods: It was a cross-sectional observational study conducted in 200 hands among 100 individuals from MBBS first and second year students studying at a Medical College. Body Mass Index (BMI) of individuals was calculated to observe the correlation between length of the dorsal venous arch and BMI.
 Results: The mean±s.d. length of dorsal venous arch in male on right hand (20.7±2.4 cm) was significantly greater than in female on right hand (19.4±2.1 cm).There was no significant difference in length of dorsal venous arch on left side between male (20.1±2.2 cm.) and female (19.3±1.8 cm).
 Conclusions: The length of the dorsal venous arch on right hand was found significantly greater in male than in female. Also the length of dorsal venous arch on right side was found to be more than on left side in both sexes. The male students are significantly older, heavier and taller than females.

OPERATION STRESS AND ITS INFLUENCE ON THE SYSTEM CHANGES IN CASE OF ABDOMINAL COMBINED TRAUMA (EXPERIMENTAL RESEARCH)

The aim of the study was to study the possibility of using a hemostatic biological haemostatic to stop bleeding from the parenchymal organs of the abdominal cavity using the surgical method of Damage control. The experiment was performed on laboratory rats that were divided into three groups: a control group, a group where, after injury, the liver wound was sutured with standard sutures and a group where the wound was plastered with a biological hemostatic agent. In order to determine the operational stress, we studied the enzymatic link of antioxidant protection - the level of catalase and superoxide dismutase. To study the indices in all experimental animals, the following tissues were taken: the lower lobe of the right lung, the proportion of the liver where the wounds were applied, the gastrocnemius muscle below the harness and the right kidney. The control points of the study were 1, 3 and 7 days after injury. During working with experimental animals, they adhered to all ethical norms established by international rules. The effect of operational stress on the enzymatic component of antioxidant protection in the tissues of the kidneys, liver, lungs and muscles was studied in the study of the combined trauma of the abdominal cavity complicated by massive bleeding and ischemic-reperfusion syndrome of the extremity. The changes in the indices of superoxide dismutase and catalase were studied. The following result was obtained: tamponing the liver wound with chitosan was a quick and effective means of temporary bleeding stop. At the same time, the duration of the operation was reduced from 19.8 to 12.5 minutes (by 36.8%) (p <0.05). Also, the level of catalase and superoxide dismutase was significantly lower in the group where the chitosan of the liver injury was used in comparison with the study group where standard stitches were applied. The deviations, which are determined in lung, liver, kidney and muscle tissues in RG-1 are evidence of the depth of their lesion and dysfunction, is a favorable factor for the further development of the triggering mechanisms of the systemic response of the body to inflammation and multiple organ failure. In contrast to the RG-2 rapid development of the systemic response was avoided. We can assume that ischemic-reperfusion syndrome is a stimulating factor in the development of systemic changes, although this statement requires further proof. It is also important to further prospective study of this topic in terms of the following questions: what effect has chitosan on liver tissue with prolonged exposure (more than 2 days) and what effect does additional injection of infusion solutions have as an agent for the treatment of hypovolemic shock.

ABSTRACT 814

Background and aims: WHO based protocol and the Pediatric Advanced Life Support approach have been used for the treatment of hypovolemic shock in Guatemala City. WHO is based in clinical findings and do not has any goal in the treatment. Aims: Identifies if in patients with severe hypovolemia, ischemia, metabolic acidosis and with absence of central pulses the fluid deficit will be higher and underestimated. Methods: Prospective, descriptive, University Hospital, hypovolemic shock related to diarrhea. Rapid cardiopulmonary evaluation of the PALS course was performed, Blood lactate was measured 0 min and 60 min after starting the fluid recovery. The goal directed therapy restore pulses, extremities warmth, capillary refill < 2 seconds, heart rate decrease, and increase in blood pressure. Monitoring for the appearance of congestive rales, hepatomegaly after the hydratation, severe edema or increment of the intrabdominal pressure. Decisions were based in perfusion restoration instead of the WHO protocol. Data processed SPSS 22;a t test for independent samples with a significant value of p < 0.05. Results: 82 children, age of 21.5 ± 34.5 months, 57 survived and 25 died. All decreased mental status. Survivors had lower HR at admission and 1 hour after, (p<0.05), higher MAP, higher pH (p<0.001), lower lactate. higher lactate depuration and base excess correction (p<0.001) All the nutritional indexes were lower in patients who died (p<0.05). Conclusions: Survivors received in the first hour 97.7 ± 42.2 ml/kg, this represents 49% more than the recommendations of the WHO protocol (p<0.001).

Anaerobic metabolism associated with traumatic hemorrhagic shock monitored by microdialysis of muscle tissue is dependent on the levels of hemoglobin and central venous oxygen saturation: a prospective, observational study

BackgroundTraumatic hemorrhagic shock resulting in tissue hypoxia is a significant cause of morbidity and mortality in polytraumatized patients. Early identification of tissue hypoxia is possible with microdialysis. The aim of this study was to determine the correlation between a marker of tissue hypoxia (L/P; lactate to pyruvate ratio) and selected parameters of systemic oxygen delivery (Hb; hemoglobin) and oxygen extraction (ScvO2; central venous oxygen saturation). We also investigated the severity of tissue hypoxia over the course of care.MethodsAdult patients with traumatic hemorrhagic shock were enrolled in this prospective, observational study. Microdialysis of the peripheral muscle tissue was performed. Demographic data and timeline of care were collected. Tissue lactate, pyruvate, glycerol, glucose levels, hemoglobin, serum lactate and oxygen saturation of the central venous blood (ScvO2) levels were also measured.ResultsThe L/P ratio trend may react to changes in systemic hemoglobin levels with a delay of 7 to 10 hours, particularly when systemic hemoglobin levels are increased by transfusion. Decrease in tissue L/P ratio may react to increase in ScvO2 with a delay of up to 10 hours, and such a decrease may signify elimination of tissue hypoxia after transfusion. We also observed changes in the L/P trend in the 13 hours preceding a change in the hemoglobin level. Fluid administration, which is routinely used as a first-line treatment of hypovolemic shock, can cause hemodilution and decreased hemoglobin. When ScvO2 decreases, increase in L/P ratio may precede the ScvO2 trend by 10 or 11 hours. An increase in the L/P ratio is an early warning sign of insufficient tissue oxygenation and should lead to intensive observation of hemoglobin levels, ScvO2 and other hemodynamic parameters. Patients who were treated more rapidly had lower maximal L/P values and a lower degree of tissue ischemia.ConclusionThe L/P ratio is useful to identify tissue ischemia and can estimate the effectiveness of fluid resuscitation. An increase in the L/P ratio is an early warning sign of inadequate tissue oxygenation and should lead to more detailed hemodynamic and laboratory monitoring. This information cannot usually be obtained from global markers.

Pediatric Hypovolemic Shock

Hypovolemic shock is a common yet underappreciated insult which often accompanies illnesses afflicting children. Indeed, it is by far the most common type of shock in the pediatric age group worldwide. Early recognition and treatment of hypovolemic shock is paramount to reversing cellular hypoxia and ischemia before irreparable end-organ

Fluid resuscitation strategy in septic shock following urinary infection with severe pulmonary capillary leakage

To characterize septic shock following urinary infection with severe pulmonary capillary leakage, and to evaluate the fluid therapy on treatment of hypovolemic shock and the role of transpulmonary thermodilution technique with pulse induced continuous cardiac output (PiCCO) monitoring. A retrospective study was conducted. Eight patients surviving septic shock following urinary infection with severe pulmonary capillary leakage were enrolled, and all of them underwent PiCCO monitoring in the intensive care unit (ICU) when the diagnosis was established. The monitoring started at admission, and ended when shock was corrected or transferred from ICU. The clinical data including general end diastolic volume index (GEDVI), extravascular lung water index (EVLWI), input and output volume of fluid, net fluid balance, oxygenation index (PaO2/FiO2), the level of arterial blood lactic acid, and chest X ray were collected and analyzed retrospectively the characteristics of septic shock following urinary infection, and the role of PiCCO monitoring in fluid resuscitation. Septic shock following urinary infection occurred in a median of 4.5 days in 8 patients after renal and ureteric calculi lithotripsy, accompanied with severe pulmonary vessel effusion and hypoxemia in different degrees. The mean value of EVLWI was (22±7) ml/kg, and the PaO2/FiO2 (164±82) mm Hg at the time of admission to ICU. Conservative fluid resuscitation strategy was adopted in management of septic shock with severe pulmonary capillary leakage, the mean fluid input in 8 patients was (2412±1121) ml/d, and the net fluid balance -553 ml/d, and the central venous pressure (CVP) and GEDVI were maintained at levels of (9±3) mm Hg and (749±236) ml/m(2) respectively. Diuretics were administered to 6 patients and the mean dosage of fursemide was (264±133) mg. Norepinephrine and dobutamine infusion were given to 7 patients to maintain blood pressure at normal range for (4±1) days. Seven patients were mechanically ventilated, and the mean length of ventilation was (8±6) days. All of the 8 patients survived from septic shock after fluid resuscitation therapy, with the mean level of EVLWI decreased gradually to (11±3) ml/kg, and the lung effusion was absorbed significantly as shown in chest X ray. The mean length of ICU stay was (17±11) days. Pearson correlate analysis showed EVLWI was significantly correlated with PaO(2)/FiO(2) and the levels of artery blood serum lactate, with r -0.91 and 0.70 respectively (both P<0.05). Successful management of septic shock following urinary infection with severe pulmonary vascular leakage is based on accurate assessment of blood volume status, especially the degree of EVLWI, emphasis on prevention of EVLWI increase, and adoption of conservative fluid resuscitation strategies according to hemodynamic monitoring parameters. PiCCO monitoring is a useful tool in assessment of the blood volume status and management of fluid resuscitation in patients with urinary lithotripsy-associated septic shock complicated with severe pulmonary edema.

1040 Evaluation of Three Resuscitation Protocols in Hypovolemic Shock Using Microcirculation Analysis in an Animal Model

Background and AimsIdeal treatment of hypovolemic shock is not well established yet. Comparison of different treatments usually focuses on global haemodynamics. Our aim was to study if microcirculation analysis shows...

Effect of Hetastarch Bolus in Trauma Patients Requiring Emergency Surgery

If blood products are not available, current military guidelines recommend a hetastarch bolus (HEX, Hextend 6% hetastarch in lactated electrolyte buffer, www. hospira.com) for initial treatment of hypovolemic shock in the field. We previously reported that a HEX bolus plus standard of care (SOC = crystalloid plus blood products) was safe during initial resuscitation in 1714 trauma patients. This study tests the hypothesis that HEX+SOC is more effective than SOC alone for volume expansion in trauma patients requiring urgent operation.From July 2009 to August 2010, the records from all adults who required emergency surgery within 4 hours of admission were screened for a retrospective cohort observational study. Burns, and those with primary neurosurgical or orthopedic indications, were excluded. The study population was comprised of 281 patients with blunt (n = 72) or penetrating (n = 209) trauma; 141 received SOC and 140 received SOC+HEX in the emergency room only (ER, n = 81) or the ER and operating room (OR, n = 59). Each case was reviewed with waiver of consent.After penetrating injury, with SOC, the injury severity score was 17 and mortality was 12%; the corresponding values in the HEX(ER) and HEX(OR) groups were 19?21 and 8%, but these apparent differences did not reach significance. However, in patients receiving HEX, initial heart rate was higher, base deficit was lower, and hematocrit was lower (consistent with relative hypovolemia), even though blood product requirements were reduced, and urine output was greater (all p < 0.05). These effects were absent in patients with blunt trauma. Platelet consumption was higher with HEX after either penetrating (p = 0.004) or blunt trauma (p = 0.045), but coagulation tests were unchanged.HEX is safe for initial resuscitation in young patients who required urgent operation after penetrating trauma, but there was no apparent effect after blunt trauma. A bolus of HEX reduced transfusion requirements without inducing coagulopathy or causing renal dysfunction, but a randomized controlled trial is necessary to eliminate the possibility of selection bias.

Reversal of hemorrhagic shock in rats using the metabolically stable thyrotropin-releasing hormone analog taltirelin hydrate

We investigated the effect of taltirelin hydrate ((−)-N-[(S)-hexahydro-1-methyl- 2,6-dioxo-4-pyrimidinyl-carbonyl]-L-histidyl-L-prolinamide tetrahydrate; taltirelin), a metabolically stable thyrotropin-releasing hormone (TRH) analog, on circulatory function, respiratory function, and viable time after bleeding in urethane-anesthetized rats. Massive volume-controlled bleeding caused marked reductions in mean arterial pressure (MAP) and respiratory rate (RR). The vital signs of control rats were lost within an average of 23 min after bleeding. Intravenous administration of taltirelin (0.03–0.3 mg/kg) and TRH (1 and 3 mg/kg) immediately after bleeding accelerated recovery of MAP and RR, and prolonged viable time in a dose-dependent manner. The potency of taltirelin in accelerating MAP and RR recovery and prolonging viable time was higher when compared with that of TRH. In addition, recovery of MAP and RR and the extension of viable time by taltirelin were inhibited by preintraperitoneal administration of atropine sulfate, which is a centrally acting muscarinic antagonist, but not by that of atropine methylbromide, which is a peripherally acting muscarinic antagonist. Taltirelin also recovered decreased arterial pH, bicarbonate ions, and base excess, and prevented a decrease in arterial oxygen saturation. In conclusion, the anti-shock effect of taltirelin was more potent than that of TRH. Taltirelin activity was mediated by the central muscarinic cholinergic system. In addition, taltirelin also corrected metabolic acidosis. These results suggest that taltirelin could be useful in the treatment of hypovolemic shock.

Hemodynamic support of the trauma patient

The aim of this review is to address and summarize some key issues and recent insights into the hemodynamic support of the trauma patient related to fluid administration. Colloids are not superior to crystalloids in treating hypovolemia in the trauma patient and show no survival benefit. Furthermore, several adverse effects (renal failure, bleeding complications and anaphylaxis) have been reported with the use of artificial colloids. Hypertonic saline is effective and well tolerated in the treatment of hypovolemic shock and traumatic brain injury. Potential benefits are reduced fluid requirements and immune modulation. Resuscitation strategies should depend on the type of injury (penetrating vs. blunt; concomitant brain injury). Excessive fluid resuscitation, which can cause acute respiratory distress syndrome, abdominal compartment syndrome and brain edema, should be avoided. Dynamic parameters to guide volume therapy are probably more reliable than static parameters and minimally invasive techniques to monitor the microcirculation are becoming more important to determine the endpoints of resuscitation. Hemodynamic support is an early goal in the treatment of the trauma patient. The use of crystalloids is currently recommended in trauma resuscitation. The amount of fluid we give should be tailored to the individual trauma patient in which clear endpoints of resuscitation are of vital importance to maximize the chances of survival.

Intravenous Infusion of Keratose‐based Fluid Induces Arteriolar Vasodilation in Cremaster Muscle of Rats

INTRODUCTIONSynthetic plasma expanders have been investigated for treatment of Hypovolemic Shock. None have proven to be more beneficial than another or as effective as whole blood. Hyperosmotic hyperviscous Keratose is proposed as a possible plasma expander. This type of compound potentiates the release of strong vasodilators and induces net intravascular transport of water, increasing circulating volume. This results in peripheral vasodilation and increased cardiac contractility which translates into lower cardiac work and better tissue perfusion. The null hypothesis was tested that a Keratose resuscitation fluid (KRF) would not induce more arteriolar vasodilation than a current plasma expander, Hetastarch (HS).METHODSA topload of KRF, HS, or PBS was infused into euvolemic rats. Changes in arteriolar diameters were measured using intravital microscopy (Fig 1).RESULTSANOVA showed significant differences (p &lt;0.05) between the three treatments. Post‐hoc comparisons showed: KRF induced greater vasodilation than PBS or HS. HS vasodilatilatory effects were not significant compared to PBS (Fig 2).DISCUSSIONKRF induced significant vasodilation in muscle microvasculature compared to HS or PBS. The use of KRF in a hemorrhage model could improve functional capillary density, a reliable index of tissue perfusion highly correlated with survival in severe hemorrhagic shock.

Increased O-linked β-N-acetylglucosamine levels on proteins improves survival, reduces inflammation and organ damage 24 hours after trauma-hemorrhage in rats

To evaluate the effects of O-linked beta-N-acetylglucosamine (O-GlcNAc) levels on survival, inflammation, and organ damage 24 hrs after trauma-hemorrhage. We have previously shown that increasing protein O-GlcNAc levels by different mechanisms reduced inflammatory responses and improved organ function 2 hrs after trauma-hemorrhage. Prospective, randomized, controlled study. Animal research laboratory. Male, adult Sprague-Dawley rats. Overnight fasted animals were subjected to either sham surgery or trauma-hemorrhage and during the resuscitation phase received glucosamine (270 mg/kg) to increase O-GlcNAc synthesis or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc, 7 mg/kg) to inhibit O-GlcNAc removal, or mannitol as control. Survival was followed up for 24 hrs. Surviving rats were euthanized and inflammatory responses, and end organ injuries were assessed. Both glucosamine and PUGNAc increased 24-hr survival compared with controls (control: 53%, GN: 85%, PUGNAc: 86%, log-rank test, p < .05). PUGNAc attenuated the trauma-hemorrhage-induced increase in serum interleukin-6 (sham surgery: 8 +/- 6, control: 181 +/- 36, PUGNAc: 42 +/- 22 pg/mL, p < .05), alanine transaminase (sham surgery: 95 +/- 14, control: 297 +/- 56, PUGNAc: 126 +/- 21 IU, p < .05), aspartate transaminase (sham surgery: 536 +/- 110, control: 1661 +/- 215, PUGNAc: 897 +/- 155 IU, p < .05), and lactate dehydrogenase (sham surgery: 160 +/- 18, control: 1499 +/- 311, PUGNAc: 357 +/- 99 IU, p < .05); however, glucosamine had no effect on these serum parameters. Furthermore, PUGNAc but not glucosamine maintained O-GlcNAc levels in liver and lung and significantly attenuated the NF-kappaB DNA activation in the liver. In the liver and heart, increased inducible nitric oxide synthase expression was also attenuated in the PUGNAc-treated group. These results demonstrate that increasing O-GlcNAc with either glucosamine or PUGNAc improved 24-hr survival after trauma-hemorrhage. However, only PUGNAc treatment attenuated significantly the subsequent tissue injury and inflammatory responses, suggesting that inhibition of O-GlcNAc removal may represent a new therapeutic approach for the treatment of hypovolemic shock.

Symposium 5: Joint BAPEN and Nutrition Society Symposium on ‘Feeding size 0: the science of starvation’ Severe malnutrition: therapeutic challenges and treatment of hypovolaemic shock

The systematic failure to recognise and appropriately treat children with severe malnutrition has been attributed to the elevated case-fatality rates, often as high as 50%, that still prevail in many hospitals in Africa. Children admitted to Kilifi District Hospital, on the coast of Kenya, with severe malnutrition frequently have life-threatening features and complications, many of which are not adequately identified or treated by WHO guidelines. Four main areas have been identified for research: early identification and better supportive care of sepsis; evidence-based fluid management strategies; improved antimicrobial treatment; rational use of nutritional strategies. The present paper focuses on the identification of children with sepsis and on fluid management strategies.

Undiagnosed Thyrotoxicosis in a Pregnant Woman with Spontaneous Renal Artery Aneurysm Rupture

Renal artery aneurysm (RAA) rupture during pregnancy is a rare event which is associated with high mortality rates for both mother and fetus. Hyperthyroidism may be present during pregnancy. Both complications are easily confused with more common conditions. We report an unusual case of a pregnant woman with undiagnosed hyperthyroidism and spontaneous RAA rupture. Thyroid storm may have been precipitated by the RAA rupture; however, the diagnosis was delayed because signs and symptoms were mistaken for those of hypovolemia. The possibility of thyrotoxicosis should be considered when mental status changes and tachycardia persist after the treatment of hypovolemic shock.