Venous Congestion Assessed by Venous Excess Ultrasound (VExUS) and Acute Kidney Injury in Children with Right Ventricular Dysfunction.

Background: Right ventricular dysfunction (RVD) is a complication following congenital cardiac surgery in children and can lead to systemic venous congestion, low cardiac output, and organ dysfunction. Venous congestion can be transmitted backwards and adversely affect encapsulated organs such as the kidneys. Primary objective: To investigate the association between systemic venous congestion, as estimated by Venous Excess Ultrasound (VExUS), and the occurrence of acute kidney injury (AKI) in children with RVD following congenital heart surgery. Secondary objectives included comparing changes in VExUS scores after initiating treatment for RVD and venous congestion. Methods and results: This was a prospective observational study in children with RVD. The VExUS study was performed on day 1, day 2, and day 3 and categorized as VExUS-1, VExUS-2, and VExUS-3. Among 43 patients with RVD and dilated inferior vena cava, 19/43 (44%), 10/43 (23%), and 12/43 (28%) were VExUS-2 and VExUS-3, respectively. There was an association between severe RVD and elevated pulmonary artery systolic pressures and a VExUS score >2. A significant association was observed between central venous pressure (CVP) measurements and VExUS. Among 31 patients with a high VExUS score >2, 18 (58%) had AKI. Additionally, improvement in CVP and fluid balance was associated with improving VExUS scores following targeted treatment for RVD. Conclusion: VExUS serves as a valuable bedside tool for diagnosing and grading venous congestion through ultrasound Doppler. An elevated VExUS score was associated with the occurrence of AKI, and among the components of VExUS, portal vein pulsatility may be useful as a predictor of AKI. How to cite this article: Natraj R, Bhaskaran AK, Rola P, Haycock K, Siuba MTT, Ranjit S. Venous Congestion Assessed by Venous Excess Ultrasound (VExUS) and Acute Kidney Injury in Children with Right Ventricular Dysfunction. Indian J Crit Care Med 2024;28(5):447-452.

Hemodynamic Management Strategies in Pediatric Septic Shock: Ten Concepts for the Bedside Practitioner.

The three pathophysiologic contributors to septic shock include varying combinations of hypovolemia (relative > absolute), decreased vascular tone or vasoplegia, and myocardial dysfunction. The three pillars of hemodynamic support include fluid boluses, vasopressors with or without inotrope infusions. The three end-points of hemodynamic resuscitation include an adequate cardiac output (CO), adequate mean arterial pressure (MAP) and diastolic blood pressure (DBP) for organ perfusion, and avoiding congestion (worse filling) parameters. Only 33-50% of septic patients show post-fluid bolus CO improvements; this may be sustained in ≥10% on account of sepsis-mediated glycocalyx injury. A pragmatic approach is to administer a small bolus (10 mL/kg over 20-30 min) and judge the response based on clinical perfusion markers, pressure elements, and congestive features. Vasoplegia marked by low DBP is a major contributor to hypotension in septic shock. Hence, a strategy of restricted fluid bolus with early low-dose norepinephrine (NE) (0.05-0.1 µg/kg/min) can be helpful. NE may also be useful in septic myocardial dysfunction (SMD) as an initial agent to maintain adequate coronary perfusion and DBP while minimizing tachycardia and providing inotropy. Severe SMD may benefit from additional inotropy (epinephrine/dobutamine). Except vasopressin, most vasoactive drugs may safely be administered via a peripheral route. The lowest MAP (5th centile for age) may be an acceptable target, provided end-organ perfusion is satisfactory. A clinical individualized approach combining the history, serial physical examination, laboratory analyses, available monitoring tools, and repeated assessment to individualize circulatory support may to lead to better outcomes than one-size-fits-all algorithms.

Haemodynamic support for paediatric septic shock: a global perspective.

Septic shock is a leading cause of hospitalisation, morbidity, and mortality for children worldwide. In 2020, the paediatric Surviving Sepsis Campaign (SSC) issued evidence-based recommendations for clinicians caring for children with septic shock and sepsis-associated organ dysfunction based on the evidence available at the time. There are now more trials from multiple settings, including low-income and middle-income countries (LMICs), addressing optimal fluid choice and amount, selection and timing of vasoactive infusions, and optimal monitoring and therapeutic endpoints. In response to developments in adult critical care to trial personalised haemodynamic management algorithms, it is timely to critically reassess the current state of applying SSC guidelines in LMIC settings. In this Viewpoint, we briefly outline the challenges to improve sepsis care in LMICs and then discuss three key concepts that are relevant to management of children with septic shock around the world, especially in LMICs. These concepts include uncertainties surrounding the early recognition of paediatric septic shock, choices for initial haemodynamic support, and titration of ongoing resuscitation to therapeutic endpoints. Specifically, given the evolving understanding of clinical phenotypes, we focus on the controversies surrounding the concepts of early fluid resuscitation and vasoactive agent use, including insights gained from experience in LMICs and high-income countries. We outline the key components of sepsis management that are both globally relevant and translatable to low-resource settings, with a view to open the conversation to the large variety of treatment pathways, especially in LMICs. We emphasise the role of simple and easily available monitoring tools to apply the SSC guidelines and to tailor individualised support to the patient's cardiovascular physiology.

Hyperferritinemia in Severe Dengue Infection: Single-Center Retrospective Cohort Study.

OBJECTIVES: Hyperferritinemia in the critical phase of dengue infections may correlate with severe dengue ( sd ) disease, and our primary objective was to examine the association between ferritin level on day 1 of PICU admission and 2009 World Health Organization (WHO) criteria for sd . Our secondary objective was outcome in relation to care. It is unclear whether immunomodulatory therapy during the critical phase may restore immune homeostasis and mitigate disease severity. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of children with dengue 1 month to 16 years old with admission ferritin greater than or equal to 500 ng/mL requiring PICU admission. Demographics, clinical, and laboratory parameters, presence of the 2009 WHO sd criteria and outcomes were analyzed. Immunomodulatory therapy was used when there was persistent hyperinflammation beyond the critical phase of plasma leakage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty-five patients were admitted in the critical phase of dengue with median (interquartile range) ferritin levels of 8,105 ng/mL (2,350-15,765 ng/mL). Patients with at least one WHO sd category had higher ferritin levels compared to those without any sd criteria, with the highest levels in eight patients with all three sd categories. In our cohort of 55, 52 patients (94%) recovered with standard supportive therapy. Recovery was associated with decreased ferritin levels that occurred in parallel with improved circulation and platelet counts; this included 22 of 24 patients with admission ferritin levels greater than or equal to 10,000 ng/mL and two with ferritin greater than 1,00,000 ng/mL. Immunomodulation was used in three patients with unremitting fever, persistent hyperferritinemia, and progressive multiple organ dysfunction beyond the critical phase, of whom two died. CONCLUSIONS: Hyperferritinemia in the critical phase of sd is associated with the number of 2009 WHO sd criteria present. Our data also indicate that many patients with sd recover well with supportive care.

BESTFIT-T3: A Tiered Monitoring Approach to Persistent/Recurrent Paediatric Septic Shock - A Pilot Conceptual Report.

Objective: Persistent shock (PS) or recurrent shock (RS) after initial fluids and vasoactives can be secondary to myriad complex mechanisms, and these patients can have a high mortality. We developed a noninvasive tiered hemodynamic monitoring approach which included, in addition to basic echocardiography, cardiac output monitoring and advanced Doppler studies to determine the etiology and provide targeted therapy of PS/RS. Design: Prospective observational study. Setting: Tertiary Care Pediatric Intensive Care Unit, India. Methods: A pilot conceptual report describing the clinical presentation of 10 children with PS/RS using advanced ultrasound and noninvasive cardiac output monitoring. Children with PS/RS after initial fluids and vasoactive agents despite basic echocardiography underwent BESTFIT + T3 (Basic Echocardiography in Shock Therapy for Fluid and Inotrope Titration) with lung ultrasound and advanced 3-tiered monitoring (T1-3). Results: Among 10/53 children with septic shock and PS/RS over a 24-month study period, BESTFIT + T3 revealed combinations of right ventricular dysfunction, diastolic dysfunction (DD), altered vascular tone, and venous congestion (VC). By integrating information obtained by BESTFIT + T1-3 and the clinical context, we were able to modify the therapeutic regimen and successfully reverse shock in 8/10 patients. Conclusion: We present our pilot results with BESTFIT + T3, a novel approach that can noninvasively interrogate major cardiac, arterial, and venous systems that may be particularly useful in regions where expensive rescue therapies are out of reach. We suggest that, with practice, intensivists already experienced in bedside POCUS can use the information obtained by BESTFIT + T3 to direct time-sensitive precision cardiovascular therapy in persistent/recurrent pediatric septic shock. How to cite this article: Natraj R, Ranjit S. BESTFIT-T3: A Tiered Monitoring Approach to Persistent/Recurrent Paediatric Septic Shock - A Pilot Conceptual Report. Indian J Crit Care Med 2022;26(7):863-870.

Variability in the Hemodynamic Response to Fluid Bolus in Pediatric Septic Shock.

OBJECTIVES: Fluid boluses are commonly administered to improve the cardiac output and tissue oxygen delivery in pediatric septic shock. The objective of this study is to evaluate the effect of an early fluid bolus administered to children with septic shock on the cardiac index and mean arterial pressure, as well as on the hemodynamic response and its relationship with outcome. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: We prospectively collected hemodynamic data from children with septic shock presenting to the emergency department or the PICU who received a fluid bolus (10 mL/kg of Ringers Lactate over 30 min). A clinically significant response in cardiac index-responder and mean arterial pressure-responder was both defined as an increase of greater than or equal to 10% 10 minutes after fluid bolus. MEASUREMENTS AND MAIN RESULTS: Forty-two children with septic shock, 1 month to 16 years old, median Pediatric Risk of Mortality-III of 13 (interquartile range, 9-19), of whom 66% were hypotensive and received fluid bolus within the first hour of shock recognition. Cardiac index- and mean arterial pressure-responsiveness rates were 31% and 38%, respectively. We failed to identify any association between cardiac index and mean arterial pressure changes (r = 0.203; p = 0.196). Cardiac function was similar in mean arterial pressure- and cardiac index-responders and nonresponders. Mean arterial pressure-responders increased systolic, diastolic, and perfusion pressures (mean arterial pressure - central venous pressure) after fluid bolus due to higher indexed systemic vascular resistance and arterial elastance index. Mean arterial pressure-nonresponders required greater vasoactive-inotrope support and had higher mortality. CONCLUSIONS: The hemodynamic response to fluid bolus in pediatric septic shock was variable and unpredictable. We failed to find a relationship between mean arterial pressure and cardiac index changes. The adverse effects of fluid bolus extended beyond fluid overload and, in some cases, was associated with reduced mean arterial pressure, perfusion pressures and higher vasoactive support. Mean arterial pressure-nonresponders had increased mortality. The response to the initial fluid bolus may be helpful to understand each patient's individualized physiologic response and guide continued hemodynamic management.

Variability in the Physiologic Response to Fluid Bolus in Pediatric Patients Following Cardiac Surgery.

BACKGROUND: Fluid boluses aiming to improve the cardiac output and oxygen delivery are commonly administered in children with shock. An increased mean arterial pressure in addition to resolution of tachycardia and improved peripheral perfusion are often monitored as clinical surrogates for improvement in cardiac output. The objective of our study is to describe changes in cardiac index, mean arterial pressure, and their relationship to other indices of cardiovascular performance. OBJECTIVE: The objective of our study is to describe changes in cardiac index, mean arterial pressure, and their relationship to other indices of cardiovascular performance. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: We prospectively analyzed hemodynamic data from children in the cardiac ICU who received fluid bolus (10mL/kg of Ringers-Lactate over 30 min) for management of shock and/or hypoperfusion within 12h of cardiac surgery. Cardiac index responders and mean arterial pressure-responders were defined as CI ≥10% and mean arterial pressure ≥10%, respectively. We evaluated the gradient for venous-return (mean systemic filling pressure-central venous pressure), arterial load properties (systemic vascular resistance index and elastance index) and changes in vasopressor support after fluid bolus. MEASUREMENTS AND MAIN RESULTS: Fifty-seven children between 1 month and 16 years (median Risk adjustment after congenital heart surgery Model for Outcome Surveillance in Australia and New Zealand score of 3.8 (interquartile range 3.7-4.6) received fluid bolus. Cardiac index-responsiveness and mean arterial pressure-responsiveness rates were 33% and 56%, respectively. No significant correlation was observed between changes in mean arterial pressure and cardiac index (r = 0.035, p = 0.79). Although the mean systemic filling pressure - central venous pressure and the number of cardiac index-responders after fluid bolus were similar, the arterial load parameters did not change in mean arterial pressure-nonresponders. Forty-three patients (75%) had a change in Vasoactive-Inotrope Score after the fluid bolus, of whom 60% received higher level of vasoactive support. CONCLUSIONS: The mean arterial pressure response to fluid bolus in cardiac ICU patients was unpredictable with a poor relationship between cardiac index-responsiveness and mean arterial pressure-responsiveness. Because arterial hypotension is frequently a trigger for administering fluids and changes in blood pressure are commonly used for tracking changes in cardiac output, we suggest a cautious and individualized approach to repeat fluid bolus based solely on lack of mean arterial pressure response to the initial fluid, since the implications include decreased arterial tone even if the cardiac index increases.

Thrombotic thrombocytopenic purpura in a 2.5-year-old boy with dengue infection: a rare complication.

Acute kidney injury (AKI) is a neglected and least studied complication of dengue. AKI secondary to thrombotic thrombocytopenic purpura (TTP) in dengue is extremely rare and there are few case reports. A 2.5-year-old boy with dengue who developed TTP in the critical phase of illness is described. He presented with microangiopathic haemolysis, thrombocytopenia and AKI. Haemolytic uraemic syndrome (HUS)/TTP was suspected and he underwent seven cycles of plasma exchange along with renal replacement therapy, following which he made a complete recovery. Prompt recognition of renal complications in dengue fever and early initiation of appropriate renal replacement therapy along with plasma exchange are essential for a good outcome.Abbreviations: AKI, acute kidney injury; GCS, Glasgow coma scale; HUS, haemolytic uraemic syndrome; LDH, lactate dehydrogenase; NS1, non-structural protein 1; pRIFLE, paediatric risk, injury, failure, loss, end-stage renal disease; SLED, sustained low-efficiency dialysis; TMA, thrombotic microangiopathy; TTP, thrombotic thrombocytopenic purpura.

Early norepinephrine decreases fluid and ventilatory requirements in pediatric vasodilatory septic shock.

AIMS: We previously reported that vasodilatation was common in pediatric septic shock, regardless of whether they were warm or cold, providing a rationale for early norepinephrine (NE) to increase venous return (VR) and arterial tone. Our primary aim was to evaluate the effect of smaller fluid bolus plus early-NE versus the American College of Critical Care Medicine (ACCM) approach to more liberal fluid boluses and vasoactive-inotropic agents on fluid balance, shock resolution, ventilator support and mortality in children with septic shock. Secondly, the impact of early NE on hemodynamic parameters, urine output and lactate levels was assessed using multimodality-monitoring. METHODS: In keeping with the primary aim, the early NE group (N-27) received NE after 30ml/kg fluid, while the ACCM group (N-41) were a historical cohort managed as per the ACCM Guidelines, where after 40-60ml/kg fluid, patients received first line vasoactive-inotropic agents. The effect of early-NE was characterized by measuring stroke volume variation(SVV), systemic vascular resistance index (SVRI) and cardiac function before and after NE, which were monitored using ECHO + Ultrasound-Cardiac-Output-Monitor (USCOM) and lactates. RESULTS: The 6-hr fluid requirement in the early-NE group (88.9+31.3 to 37.4+15.1ml/kg), and ventilated days [median 4 days (IQR 2.5-5.25) to 1day (IQR 1-1.7)] were significantly less as compared to the ACCM group. However, shock resolution and mortality rates were similar. In the early NE group, the overall SVRI was low (mean 679.7dynes/sec/cm5/m2, SD 204.5), and SVV decreased from 23.8±8.2 to 18.5±9.7, p=0.005 with NE infusion suggesting improved preload even without further fluid loading. Furthermore, lactate levels decreased and urine-output improved. CONCLUSION: Early-NE and fluid restriction may be of benefit in resolving shock with less fluid and ventilator support as compared to the ACCM approach.