The Effect of Early Norepinephrine on Stroke Volume Index, Cardiac Index, Lactate, and Arterial Elastance in Pediatric Septic Shock

NCT06461390 | Completed Phase 2 DMC

• 1 other identifier: 23-12-2106
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The complexity of pediatric septic shock arise from its varied pathophysiology, which includes systemic inflammation, cardiovascular collapse, and multiple organ dysfunction. Current standard treatments, which primarily focusedon fluid resuscitation, had exhibited several problems. Excessive fluid resuscitation has been associated with complications such as fluid overload, which may cause conditions such as pulmonary edema and organ dysfunction, leading to worsened outcomes. This emphasizes the need for alternative therapeutic strategies that can effectively manage hemodynamic instability while minimizing the risks of fluid overload. In adult patients, the early use of vasopressors has been recommended to restore perfusion in patients with septic shock, compared to repeated fluid loading. However, previous research on the use of norepinephrine and the preload status of the pediatric population is still limited. In addition, the use of fluid resuscitation does not always exhibit the desirable response, which is the increase of blood pressure. This is because the blood pressure depends not only on the stroke volume but also the vascular resistance. Consequently, predicting blood pressure elevation after fluid resuscitation remains challenging. Based on previous research, arterial elastance has the potential to predict the increase of blood pressure in response to fluid administration. Thus, this study aimed to investigate the effects of early administration of fluid resuscitation combined with norepinephrine in pediatric septic shock patients and evaluate the useof arterial elastance as a predictor of blood pressure response following fluid resuscitation. Finally, this study will also evaluate the parameters such as stroke volume index, cardiac index, lactate clearance , arterial elastance in pediatric patients with septic shock who were resuscitated using the hemodynamic support guidelines according to the Surviving Sepsis Campaign protocols.

Conditions

Septic Shock; Sepsis

Keywords

pediatric septic shock; pulmonary edema; early norepinephrine; fluid loading

Outcome Measures

Primary Outcomes (3)

• stroke volume index

  Evaluate the changes in stroke volume index using Ultrasonic Cardiac Output Monitor (USCOM), in units ml/m2, between the pediatric septic shock patients receiving fluid loading with early norepinephrine compared to those who only receive fluid loading

  evaluate one hour after intervention

• cardiac index

  Evaluate the changes in cardiac index Ultrasonic Cardiac Output Monitor (USCOM), in units L/m2/minute,between the pediatric septic shock patients receiving fluid loading with early norepinephrine compared to those who only receive fluid loading

  evaluate one hour after intervention

• Lactate

  Lactate clearance is defined as the change in lactate levels between two time points and is expressed as a 10-20% reduction in lactate per hour or a reduction of at least 10% within 6 hours during initial resuscitation

  evaluate one hour after intervention

Secondary Outcomes (2)

• arterial elastance

  evaluate one hour after intervention

• pulmonary edema

  evaluate one hour after intervention

Study Arms (2)

Norepinephrine Group (Fluid loading with early norepinephrine administration group)

EXPERIMENTAL

NE Group will receive ringer lactate bolus 20 ml/kg along with norepinephrine infusion at 0.1 mcg/kg/ minute until MAP\>5 percentile. Additional fluid boluses of 10-20 ml/kg will be administered (up to a total of 60 ml/kg) until shock resolution or signs of fluid overload are observed, with or without continued norepinephrine infusion according to the treatment group

Drug: Norepinephrine

Ringer's lactate Group

ACTIVE COMPARATOR

The Fluid Group will receive only ringer lactate bolus 20 ml/kg. Additional fluid boluses of 10-20 ml/kg will be administered (up to a total of 60 ml/kg) until shock resolution or signs of fluid overload are observed.

Drug: Ringer's Lactate

Interventions

Norepinephrine DRUG

NE Group (Fluid loading with early norepinephrine administration group) NE Group will receive ringer lactate bolus 20 ml/kg along with norepinephrine infusion at 0.1 mcg/kg/minute until MAP\>5 percentile. Additional fluid boluses of 10-20 ml/kg will be administered (up to a total of 60 ml/kg) until shock resolution or signs of fluid overload are observed, with or without continued norepinephrine infusion according to the treatment group

Norepinephrine Group (Fluid loading with early norepinephrine administration group)

Ringer's Lactate DRUG

Fluid Group will receive ringer lactate bolus 20 ml/ kg only. Additional fluid boluses of 10-20 ml/kg will be administered (up to a total of 60 ml/kg) until shock resolution or signs of fluid overload are observed

Ringer's lactate Group

Eligibility Criteria

• Age: 3 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients aged 3 months to 18 years with critical condition
• Suspected or confirmed infection, indicated by fever accompanied by signs of shock:
• Mean arterial pressure 5th percentile, or
• Systolic pressure ≤ 5th percentile, or
• Diastolic pressure ≤ 5th percentile, or
• Wide pulse pressure (diastolic pressure \< half of systolic pressure), or
• Tachycardia accompanied by one or more of the following signs: Altered mental status, capillary refill time \> 2 seconds, temperature difference between extremities and core body, weaker peripheral arterial pulsation compared to the central pulsation, bounding pulse, mottled skin.

You may not qualify if:

• Contraindication of fluid loading (signs of fluid overload)
• Burn injury, massive bleeding, dengue hemorrhagic fever.
• Cardiogenic shock.
• Deep anesthesia.

Sponsors & Collaborators

• Indonesia University: lead

Study Sites (1)

Cipto Mangunkusumo Hospital

Jakarta Pusat, DKI Jakarta, 10440, Indonesia

Location

Related Publications (5)

• Sugimoto M, Manabe H, Nakau K, Furuya A, Okushima K, Fujiyasu H, Kakuya F, Goh K, Fujieda K, Kajino H. The role of N-terminal pro-B-type natriuretic peptide in the diagnosis of congestive heart failure in children. - Correlation with the heart failure score and comparison with B-type natriuretic peptide -. Circ J. 2010 May;74(5):998-1005. doi: 10.1253/circj.cj-09-0535. Epub 2010 Apr 6.

  PMID: 20378998 BACKGROUND

• Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, Nyeko R, Mtove G, Reyburn H, Lang T, Brent B, Evans JA, Tibenderana JK, Crawley J, Russell EC, Levin M, Babiker AG, Gibb DM; FEAST Trial Group. Mortality after fluid bolus in African children with severe infection. N Engl J Med. 2011 Jun 30;364(26):2483-95. doi: 10.1056/NEJMoa1101549. Epub 2011 May 26.

  PMID: 21615299 RESULT

• Macdonald S, Peake SL, Corfield AR, Delaney A. Fluids or vasopressors for the initial resuscitation of septic shock. Front Med (Lausanne). 2022 Nov 24;9:1069782. doi: 10.3389/fmed.2022.1069782. eCollection 2022.

  PMID: 36507525 RESULT

• Garcia MI, Romero MG, Cano AG, Aya HD, Rhodes A, Grounds RM, Cecconi M. Dynamic arterial elastance as a predictor of arterial pressure response to fluid administration: a validation study. Crit Care. 2014 Nov 19;18(6):626. doi: 10.1186/s13054-014-0626-6.

  PMID: 25407570 RESULT

• Choudhary R, Sitaraman S, Choudhary A. Lactate clearance as the predictor of outcome in pediatric septic shock. J Emerg Trauma Shock. 2017 Apr-Jun;10(2):55-59. doi: 10.4103/JETS.JETS_103_16.

  PMID: 28367008 RESULT

MeSH Terms

Conditions

Shock, Septic; Sepsis; Pulmonary Edema

Interventions

Norepinephrine; Ringer's Lactate

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: fluid loading with norepinephrie
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatrician

Model Details: Interventional subject will be received fluid loading with early norepinephrine administration with dose 0.1 mcg/kgBW/minute control subject will be received fluid loading only

Study Record Dates

• First Submitted: June 4, 2024
• First Posted: June 17, 2024
• Study Start: March 25, 2024
• Primary Completion: May 31, 2024
• Study Completion: May 31, 2024
• Last Updated: June 20, 2024

Record last verified: 2024-06

Locations

ID (1)