Blood volume and hemodynamics during treatment of major hemorrhage with Ringer solution, 5% albumin, and 20% albumin: a single-center randomized controlled trial.

BACKGROUND: Volume replacement with crystalloid fluid is the conventional treatment of hemorrhage. We challenged whether a standardized amount of 5% or 20% albumin could be a viable option to maintain the blood volume during surgery associated with major hemorrhage. Therefore, the aim of this study was to quantify and compare the plasma volume expansion properties of 5% albumin, 20% albumin, and Ringer-lactate, when infused during major surgery. METHODS: In this single-center randomized controlled trial, fluid replacement therapy to combat hypovolemia during the hemorrhagic phase of cystectomy was randomly allocated in 42 patients to receive either 5% albumin (12 mL/kg) or 20% albumin (3 mL/kg) over 30 min at the beginning of the hemorrhagic phase, both completed by a Ringer-lactate replacing blood loss in a 1:1 ratio, or Ringer-lactate alone to replace blood loss in a 3:1 ratio. Measurements of blood hemoglobin over 5 h were used to estimate the effectiveness of each fluid to expand the blood volume using the following regression equation: blood loss plus blood volume expansion = factor + volume of infused albumin + volume of infused Ringer-lactate. RESULTS: The median hemorrhage was 848 mL [IQR: 615-1145]. The regression equation showed that the Ringer-lactate solution expanded the plasma volume by 0.18 times the infused volume while the corresponding power of 5% and 20% albumin was 0.74 and 2.09, respectively. The Ringer-lactate only fluid program resulted in slight hypovolemia (mean, - 313 mL). The 5% and 20% albumin programs were more effective in filling the vascular system; this was evidenced by blood volume changes of only + 63 mL and - 44 mL, respectively, by long-lasting plasma volume expansion with median half time of 5.5 h and 4.8 h, respectively, and by an increase in the central venous pressure. CONCLUSION: The power to expand the plasma volume was 4 and almost 12 times greater for 5% albumin and 20% albumin than for Ringer-lactate, and the effect was sustained over 5 h. The clinical efficacy of albumin during major hemorrhage was quite similar to previous studies with no hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov NCT05391607, date of registration May 26, 2022.

A case of septic shock due to delayed diagnosis of Cryptosporidium infection after liver transplantation.

BACKGROUND: Cryptosporidium is recognized as a significant pathogen of diarrhea disease in immunocompromised hosts, and studies have shown that Cryptosporidium infection is high in solid organ transplantation (SOT) patients and often has serious consequences. Because of the lack of specificity of diarrheasymptoms cased by Cryptosporidium infection, it is rarely reported in patients undergoing liver transplantation (LT). It frequently delays diagnosis, coming with severe consequences. In clinical work, diagnosing Cryptosporidium infection in LT patients is also complex but single, and the corresponding anti-infective treatment regimen has not yet been standardized. A rare case of septic shock due to a delayed diagnosis of Cryptosporidium infection after LT and relevant literature are discussed in the passage. CASE PRESENTATION: A patient who had received LT for two years was admitted to the hospital with diarrhea more than 20 days after eating an unclean diet. After failing treatment at a local hospital, he was admitted to Intensive Care Unit after going into septic shock. The patient presented hypovolemia due to diarrhea, which progressed to septic shock. The patient's sepsis shock was controlled after receiving multiple antibiotic combinations and fluid resuscitation. However, the persistent diarrhea, as the culprit of the patient's electrolyte disturbance, hypovolemia, and malnutrition, was unsolved. The causative agent of diarrhea, Cryptosporidium infection, was identified by colonoscopy, faecal antacid staining, and blood high-throughput sequencing (NGS). The patient was treated by reducing immunosuppression and Nitazoxanide (NTZ), which proved effective in this case. CONCLUSION: When LT patients present with diarrhea, clinicians should consider the possibility of Cryptosporidium infection, in addition to screening for conventional pathogens. Tests such as colonoscopy, stool antacid staining and blood NGS sequencing can help diagnose and treat of Cryptosporidium infection early and avoid serious consequences of delayed diagnosis. In treating Cryptosporidium infection in LT patients, the focus should be on the patient's immunosuppressive therapy, striking a balance between anti-immunorejection and anti-infection should be sought. Based on practical experience, NTZ therapy in combination with controlled CD4 + T cells at 100-300/mm3 was highly effective against Cryptosporidium without inducing immunorejection.

Management of Hyperosmolar Hyperglycaemic State (HHS) in Adults: An updated guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care Group.

Hyperosmolar Hyperglycaemic State (HHS) is a medical emergency associated with high mortality. It occurs less frequently than diabetic ketoacidosis (DKA), affects those with pre-existing/new type 2 diabetes mellitus and increasingly affecting children/younger adults. Mixed DKA/HHS may occur. The JBDS HHS care pathway consists of 3 themes (clinical assessment and monitoring, interventions, assessments and prevention of harm) and 5 phases of therapy (0-60 min, 1-6, 6-12, 12-24 and 24-72 h). Clinical features of HHS include marked hypovolaemia, osmolality ≥320 mOsm/kg using [(2×Na+ ) + glucose+urea], marked hyperglycaemia ≥30 mmol/L, without significant ketonaemia (≤3.0 mmol/L), without significant acidosis (pH >7.3) and bicarbonate ≥15 mmol/L. Aims of the therapy are to improve clinical status/replace fluid losses by 24 h, gradual decline in osmolality (3.0-8.0 mOsm/kg/h to minimise the risk of neurological complications), blood glucose 10-15 mmol/L in the first 24 h, prevent hypoglycaemia/hypokalaemia and prevent harm (VTE, osmotic demyelination, fluid overload, foot ulceration). Underlying precipitants must be identified and treated. Interventions include: (1) intravenous (IV) 0.9% sodium chloride to restore circulating volume (fluid losses 100-220 ml/kg, caution in elderly), (2) fixed rate intravenous insulin infusion (FRIII) should be commenced once osmolality stops falling with fluid replacement unless there is ketonaemia (FRIII should be commenced at the same time as IV fluids). (3) glucose infusion (5% or 10%) should be started once glucose <14 mmol/L and (4) potassium replacement according to potassium levels. HHS resolution criteria are: osmolality <300 mOsm/kg, hypovolaemia corrected (urine output ≥0.5 ml/kg/h), cognitive status returned to pre-morbid state and blood glucose <15 mmol/L.

PragmaTic, prospEctive, randomized, controlled, double-blind, mulTi-centre, multinational study on the safety and efficacy of a 6% HydroxYethyl Starch (HES) solution versus an electrolyte solution in trauma patients: study protocol for the TETHYS study.

BACKGROUND: Trauma may be associated with significant to life-threatening blood loss, which in turn may increase the risk of complications and death, particularly in the absence of adequate treatment. Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss to maintain or re-establish hemodynamic stability with the ultimate goal to avoid organ hypoperfusion and cardiovascular collapse. The current study compares a 6% HES 130 solution (Volulyte 6%) versus an electrolyte solution (Ionolyte) for volume replacement therapy in adult patients with traumatic injuries, as requested by the European Medicines Agency to gain more insights into the safety and efficacy of HES in the setting of trauma care. METHODS: TETHYS is a pragmatic, prospective, randomized, controlled, double-blind, multicenter, multinational trial performed in two parallel groups. Eligible consenting adults ≥ 18 years, with an estimated blood loss of ≥ 500 ml, and in whom initial surgery is deemed necessary within 24 h after blunt or penetrating trauma, will be randomized to receive intravenous treatment at an individualized dose with either a 6% HES 130, or an electrolyte solution, for a maximum of 24 h or until reaching the maximum daily dose of 30 ml/kg body weight, whatever occurs first. Sample size is estimated as 175 patients per group, 350 patients total (α = 0.025 one-tailed, power 1-ß = 0.8). Composite primary endpoint evaluated in an exploratory manner will be 90-day mortality and 90-day renal failure, defined as AKIN stage ≥ 2, RIFLE injury/failure stage, or use of renal replacement therapy (RRT) during the first 3 months. Secondary efficacy and safety endpoints are fluid administration and balance, changes in vital signs and hemodynamic status, changes in laboratory parameters including renal function, coagulation, and inflammation biomarkers, incidence of adverse events during treatment period, hospital, and intensive care unit (ICU) length of stay, fitness for ICU or hospital discharge, and duration of mechanical ventilation and/or RRT. DISCUSSION: This pragmatic study will increase the evidence on safety and efficacy of 6% HES 130 for treatment of hypovolemia secondary to acute blood loss in trauma patients. TRIAL REGISTRATION: Registered in EudraCT, No.: 2016-002176-27 (21 April 2017) and ClinicalTrials.gov, ID: NCT03338218 (09 November 2017).

Humerus Intraosseous and Intravenous Administration of Epinephrine in Normovolemic and Hypovolemic Cardiac Arrest Porcine Models.

OBJECTIVE: The aim of this study was to compare area under the curve (AUC), frequency, and odds of return of spontaneous circulation (ROSC) when epinephrine was administered in hypovolemic and normovolemic cardiac arrest models. METHODS: Twenty-eight adult swine were randomly assigned to 4 groups: HIO Normovolemia Group (HIONG); HIO Hypovolemia Group (HIOHG); IV Normovolemia (IVNG); and IV Hypovolemia Group (IVHG). Swine were anesthetized. The HIOH and IVH subjects were exsanguinated 35% of their blood volume. Each was placed into arrest. After 2 minutes, cardiopulmonary resuscitation was initiated. After another 2 minutes, 1 mg of epinephrine was given by IV or HIO routes; blood samples were collected over 5 minutes and analyzed by high-performance liquid chromatography. Subjects were defibrillated every 2 minutes. RESULTS: The AUC in the HIOHG was significantly less than both the HIONG (p = 0.047) and IVHG (p = 0.021). There were no other significant differences in the groups relative to AUC (p > 0.05). HIONG had a significantly higher occurrence of ROSC compared to HIOHG (p = 0.018) and IVH (p =0.018) but no other significant differences (p > 0.05). The odds of ROSC were 19.2 times greater for HIONG compared to the HIOHG. CONCLUSION: The study strongly supports the effectiveness of HIO administration of epinephrine and should be considered as a first-line intervention for patients in cardiac arrest related to normovolemic causes. However, our findings do not support using HIO access for epinephrine administration for patients in cardiac arrest related to hypovolemic reasons.

Tibial Intraosseous Administration of Epinephrine Is Effective in Restoring Return of Spontaneous Circulation in a Pediatric Normovolemic But Not Hypovolemic Cardiac Arrest Model.

OBJECTIVE: We compared the efficacy of tibial intraosseous (TIO) administration of epinephrine in a pediatric normovolemic versus hypovolemic cardiac arrest model to determine the incidence of return of spontaneous circulation (ROSC) and plasma epinephrine concentrations over time. METHODS: This experimental study evaluated the pharmacokinetics of epinephrine and/or incidence of ROSC after TIO administration in either a normovolemic or hypovolemic pediatric swine model. RESULTS: All subjects in the TIO normovolemia cardiac arrest group experienced ROSC after TIO administration of epinephrine. In contrast, subjects experiencing hypovolemia and cardiac arrest were significantly less likely to experience ROSC when epinephrine was administered TIO versus intravenous (TIO hypovolemia: 14% [1/7] vs IV hypovolemia: 71% [5/7]; P = 0.031). The TIO hypovolemia group exhibited significantly lower plasma epinephrine concentrations versus IV hypovolemia at 60, 90, 120, and 150 seconds (P < 0.05). Although the maximum concentration of plasma epinephrine was similar, the TIO hypovolemia group exhibited significantly slower time to maximum concentration times versus TIO normovolemia subjects (P = 0.004). CONCLUSIONS: Tibial intraosseous administration of epinephrine reliably facilitated ROSC among normovolemic cardiac arrest pediatric patients, which is consistent with published reports. However, TIO administration of epinephrine was ineffective in restoring ROSC among subjects experiencing hypovolemia and cardiac arrest. Tibial intraosseous-administered epinephrine during hypovolemia and cardiac arrest may have resulted in a potential sequestration of epinephrine in the tibia. Central or peripheral intravascular access attempts should not be abandoned after successful TIO placement in the resuscitation of patients experiencing concurrent hypovolemia and cardiac arrest.

Similar hemostatic responses to hypovolemia induced by hemorrhage and lower body negative pressure reveal a hyperfibrinolytic subset of non-human primates.

BACKGROUND: To study central hypovolemia in humans, lower body negative pressure (LBNP) is a recognized alternative to blood removal (HEM). While LBNP mimics the cardiovascular responses of HEM in baboons, similarities in hemostatic responses to LBNP and HEM remain unknown in this species. METHODS: Thirteen anesthetized baboons were exposed to progressive hypovolemia by HEM and, four weeks later, by LBNP. Hemostatic activity was evaluated by plasma markers, thromboelastography (TEG), flow cytometry, and platelet aggregometry at baseline (BL), during and after hypovolemia. RESULTS: BL values were indistinguishable for most parameters although platelet count, maximal clot strength (MA), protein C, thrombin anti-thrombin complex (TAT), thrombin activatable fibrinolysis inhibitor (TAFI) activity significantly differed between HEM and LBNP. Central hypovolemia induced by either method activated coagulation; TEG R-time decreased and MA increased during and after hypovolemia compared to BL. Platelets displayed activation by flow cytometry; platelet count and functional aggregometry were unchanged. TAFI activity and protein, Factors V and VIII, vWF, Proteins C and S all demonstrated hemodilution during HEM and hemoconcentration during LBNP, whereas tissue plasminogen activator (tPA), plasmin/anti-plasmin complex, and plasminogen activator inhibitor-1 did not. Fibrinolysis (TEG LY30) was unchanged by either method; however, at BL, fibrinolysis varied greatly. Post-hoc analysis separated baboons into low-lysis (LY30 <2%) or high-lysis (LY30 >2%) whose fibrinolytic state matched at both HEM and LBNP BL. In high-lysis, BL tPA and LY30 correlated strongly (r = 0.95; P<0.001), but this was absent in low-lysis. In low-lysis, BL TAFI activity and tPA correlated (r = 0.88; P<0.050), but this was absent in high-lysis. CONCLUSIONS: Central hypovolemia induced by either LBNP or HEM resulted in activation of coagulation; thus, LBNP is an adjunct to study hemorrhage-induced pro-coagulation in baboons. Furthermore, this study revealed a subset of baboons with baseline hyperfibrinolysis, which was strongly coupled to tPA and uncoupled from TAFI activity.

Altered Cerebral Blood Flow and Potential Neuroprotective Effect of Human Relaxin-2 (Serelaxin) During Hypoxia or Severe Hypovolemia in a Sheep Model.

Specific neuroprotective strategies to minimize cerebral damage caused by severe hypoxia or hypovolemia are lacking. Based on previous studies showing that relaxin-2/serelaxin increases cortical cerebral blood flow, we postulated that serelaxin might provide a neuroprotective effect. Therefore, we tested serelaxin in two emergency models: hypoxia was induced via inhalation of 5% oxygen and 95% nitrogen for 12 min; thereafter, the animals were reoxygenated. Hypovolemia was induced and maintained for 20 min by removal of 50% of the total blood volume; thereafter, the animals were retransfused. In each damage model, the serelaxin group received an intravenous injection of 30 µg/kg of serelaxin in saline, while control animals received saline only. Blood gases, shock index values, heart frequency, blood pressure, and renal blood flow showed almost no significant differences between control and treatment groups in both settings. However, serelaxin significantly blunted the increase of lactate during hypovolemia. Serelaxin treatment resulted in significantly elevated cortical cerebral blood flow (CBF) in both damage models, compared with the respective control groups. Measurements of the neuroproteins S100B and neuron-specific enolase in cerebrospinal fluid revealed a neuroprotective effect of serelaxin treatment in both hypoxic and hypovolemic animals, whereas in control animals, neuroproteins increased during the experiment. Western blotting showed the expression of relaxin receptors and indicated region-specific differences in relaxin receptor-mediated signaling in cortical and subcortical brain arterioles, respectively. Our findings support the hypothesis that serelaxin is a potential neuroprotectant during hypoxia and hypovolemia. Due to its preferential improvement of cortical CBF, serelaxin might reduce cognitive impairments associated with these emergencies.

Respuesta de los autores: Acerca del papel del ácido tranexámico en pacientes con traumatismo en urgencias y emergencias / Authors' reply: On the role of tranexamic acid in emergency department patients with trauma

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Clinical Practice Guideline: Maintenance Intravenous Fluids in Children.

Maintenance intravenous fluids (IVFs) are used to provide critical supportive care for children who are acutely ill. IVFs are required if sufficient fluids cannot be provided by using enteral administration for reasons such as gastrointestinal illness, respiratory compromise, neurologic impairment, a perioperative state, or being moribund from an acute or chronic illness. Despite the common use of maintenance IVFs, there is high variability in fluid prescribing practices and a lack of guidelines for fluid composition administration and electrolyte monitoring. The administration of hypotonic IVFs has been the standard in pediatrics. Concerns have been raised that this approach results in a high incidence of hyponatremia and that isotonic IVFs could prevent the development of hyponatremia. Our goal in this guideline is to provide an evidence-based approach for choosing the tonicity of maintenance IVFs in most patients from 28 days to 18 years of age who require maintenance IVFs. This guideline applies to children in surgical (postoperative) and medical acute-care settings, including critical care and the general inpatient ward. Patients with neurosurgical disorders, congenital or acquired cardiac disease, hepatic disease, cancer, renal dysfunction, diabetes insipidus, voluminous watery diarrhea, or severe burns; neonates who are younger than 28 days old or in the NICU; and adolescents older than 18 years old are excluded. We specifically address the tonicity of maintenance IVFs in children.The Key Action Statement of the subcommittee is as follows:1A: The American Academy of Pediatrics recommends that patients 28 days to 18 years of age requiring maintenance IVFs should receive isotonic solutions with appropriate potassium chloride and dextrose because they significantly decrease the risk of developing hyponatremia (evidence quality: A; recommendation strength: strong).

Assessing adherence to current national guidelines for appropriate albumin use at an academic medical center

Objective: To assess adherence to current national guidelines for appropriate albumin use at an academic medical center. Methods: This retrospective chart review of 150 randomly selected patients prescribed and administered at least one dose of albumin was conducted in an urban academic medical center to evaluate the adherence of albumin orders to current national guidelines. Inclusion criteria consisted of discharged patients at least 18-years-old admitted to the intensive care unit or medical/surgical unit from September 1, 2015 to August 31, 2016. The primary outcome was the number of patients who inappropriately received albumin based on national guidelines and FDA approved indications. Secondary outcomes included the number of patients who received the incorrect concentration or dose of albumin based on indication, as well as the cost associated with inappropriate albumin prescribing. Descriptive statistics were used to report outcomes. Results: There were 68 instances (45%) where albumin was prescribed inappropriately according to guideline recommendations. Of the 82 instances where albumin was used appropriately, 18 patients received an incorrect dose (22%), and 6 received the inappropriate concentration of albumin (7%). The cost for the 150 patients included in the study associated with inappropriate albumin prescribing was approximately $13,000. Conclusions: This study identified areas for pharmacist intervention to ensure appropriate albumin utilization, as well as proper dosing for the most frequently incorrectly dosed indications, including hepato-renal syndrome, spontaneous bacterial peritonitis, and paracentesis. This study also identified an unexpected indication with significant inappropriate albumin utilization, perioperative hypotension, which is an area for further intervention to monitor and decrease use

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Pulmonary hemodynamic effects and pulmonary arterial compliance during hypovolemic shock and reinfusion with human relaxin-2 (serelaxin) treatment in a sheep model.

BACKGROUND: Previous studies on the recombinant form of human relaxin-2 (serelaxin) have shown a decrease of pulmonary hemodynamics after serelaxin injection. Currently, the effect of serelaxin treatment during hypovolemia in a large animal model remains mostly unknown. METHODS: 12 sheep were randomly assigned to a sham or serelaxin (30µg/kg serelaxin) group and underwent right heart catheterization. 50% of the estimated total blood volume were removed to induce hypovolemia, and subsequently retransfused 20 min later (reinfusion). Blood gases, heart rate, peripheral and pulmonary arterial oxygen saturation, systolic, diastolic and mean values of both pulmonary artery pressure (PAP) and pulmonary capillary wedge pressure (PCW) were measured. Cardiac output (CO), pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAcompl) and systemic vascular resistance (SVR) were calculated. RESULTS: Hypovolemia and shock led to a similar decrease of PAP and PCW in both groups (p≤0.001). CO, SV and PAcompl decreased only in the control group (p≤0.05) and remained higher in the serelaxin-treated group. The results of this study suggest that serelaxin treatment did not negatively influence hemodynamic parameters during hypovolemic shock. CONCLUSION: The main conclusion of this study is that cardiopulmonary adaption mechanisms are not critically altered by serelaxin administration during severe hypovolemia and retransfusion.

6% Hydroxyethyl starch (HES 130/0.4) diminishes glycocalyx degradation and decreases vascular permeability during systemic and pulmonary inflammation in mice.

BACKGROUND: Increased vascular permeability is a pathophysiological hallmark of sepsis and results in increased transcapillary leakage of plasma fluid, hypovolemia, and interstitial edema formation. 6% hydroxyethyl starch (HES 130/0.4) is commonly used to treat hypovolemia to maintain adequate organ perfusion and oxygen delivery. The present study was designed to investigate the effects of 6% HES 130/0.4 on glycocalyx integrity and vascular permeability in lipopolysaccharide (LPS)-induced pulmonary inflammation and systemic inflammation in mice. METHODS: 6% HES 130/0.4 or a balanced electrolyte solution (20 ml/kg) was administered intravenously 1 h after cecal ligation and puncture (CLP) or LPS inhalation. Sham-treated animals receiving 6% HES 130/0.4 or the electrolyte solution served as controls. The thickness of the endovascular glycocalyx was visualized by intravital microscopy in lung (LPS inhalation model) or cremaster muscle (CLP model). Syndecan-1, hyaluronic acid, and heparanase levels were measured in blood samples. Vascular permeability in the lungs, liver, kidney, and brain was measured by Evans blue extravasation. RESULTS: Both CLP induction and LPS inhalation resulted in increased vascular permeability in the lung, liver, kidney, and brain. 6% HES 130/0.4 infusion led to significantly reduced plasma levels of syndecan-1, heparanase, and hyaluronic acid, which was accompanied by a preservation of the glycocalyx thickness in postcapillary venules of the cremaster (0.78 ± 0.09 µm vs. 1.39 ± 0.10 µm) and lung capillaries (0.81 ± 0.09 µm vs. 1.49 ± 0.12 µm). CONCLUSIONS: These data suggest that 6% HES 130/0.4 exerts protective effects on glycocalyx integrity and attenuates the increase of vascular permeability during systemic inflammation.

Colloids and the Microcirculation.

Colloid solutions have been advocated for use in treating hypovolemia due to their expected effect on improving intravascular retention compared with crystalloid solutions. Because the ultimate desired effect of fluid resuscitation is the improvement of microcirculatory perfusion and tissue oxygenation, it is of interest to study the effects of colloids and crystalloids at the level of microcirculation under conditions of shock and fluid resuscitation, and to explore the potential benefits of using colloids in terms of recruiting the microcirculation under conditions of hypovolemia. This article reviews the physiochemical properties of the various types of colloid solutions (eg, gelatin, dextrans, hydroxyethyl starches, and albumin) and the effects that they have under various conditions of hypovolemia in experimental and clinical scenarios.

Are we close to the ideal intravenous fluid?

The approach to i.v. fluid therapy for hypovolaemia may significantly influence outcomes for patients who experience a systemic inflammatory response after sepsis, trauma, or major surgery. Currently, there is no single i.v. fluid agent that meets all the criteria for the ideal treatment for hypovolaemia. The physician must choose the best available agent(s) for each patient, and then decide when and how much to administer. Findings from large randomized trials suggest that some colloid-based fluids, particularly starch-based colloids, may be harmful in some situations, but it is unclear whether they should be withdrawn from use completely. Meanwhile, crystalloid fluids, such as saline 0.9% and Ringer's lactate, are more frequently used, but debate continues over which preparation is preferable. Perhaps most importantly, it remains unclear how to select the optimal dose of fluid in different patients and different clinical scenarios. There is good reason to believe that both inadequate and excessive i.v. fluid administration may lead to poor outcomes, including increased risk of infection and organ dysfunction, for hypovolaemic patients. In this review, we summarize the current knowledge on this topic and identify some key pitfalls and some areas of agreed best practice.

Myocardial and haemodynamic responses to two fluid regimens in African children with severe malnutrition and hypovolaemic shock (AFRIM study).

BACKGROUND: Fluid therapy in severely malnourished children is hypothesized to be deleterious owing to compromised cardiac function. We evaluated World Health Organization (WHO) fluid resuscitation guidelines for hypovolaemic shock using myocardial and haemodynamic function and safety endpoints. METHODS: A prospective observational study of two sequential fluid management strategies was conducted at two East African hospitals. Eligible participants were severely malnourished children, aged 6-60 months, with hypovolaemic shock secondary to gastroenteritis. Group 1 received up to two boluses of 15 ml/kg/h of Ringer's lactate (RL) prior to rehydration as per WHO guidelines. Group 2 received rehydration only (10 ml/kg/h of RL) up to a maximum of 5 h. Comprehensive clinical, haemodynamic and echocardiographic data were collected from admission to day 28. RESULTS: Twenty children were enrolled (11 in group 1 and 9 in group 2), including 15 children (75%) with kwashiorkor, 8 (40%) with elevated brain natriuretic peptide >300 pg/ml, and 9 (45%) with markedly elevated median systemic vascular resistance index (SVRI) >1600 dscm-5/m2 indicative of severe hypovolaemia. Echocardiographic evidence of fluid-responsiveness (FR) was heterogeneous in group 1, with both increased and decreased stroke volume and myocardial fractional shortening. In group 2, these variables were more homogenous and typical of FR. Median SVRI marginally decreased post fluid administration (both groups) but remained high at 24 h. Mortality at 48 h and to day 28, respectively, was 36% (4 deaths) and 81.8% (9 deaths) in group 1 and 44% (4 deaths) and 55.6% (5 deaths) in group 2. We observed no pulmonary oedema or congestive cardiac failure on or during admission; most deaths were unrelated to fluid interventions or echocardiographic findings of response to fluids. CONCLUSION: Baseline and cardiac response to fluid resuscitation do not indicate an effect of compromised cardiac function on response to fluid loading or that fluid overload is common in severely malnourished children with hypovolaemic shock. Endocrine response to shock and persistently high SVRI post fluid-therapy resuscitation may indicate a need for further research investigating enhanced fluid volumes to adequately correct volume deficit. The adverse outcomes are concerning, but appear to be unrelated to immediate fluid management.