Plasma Exchange in Children With Severe Sepsis and Septic Shock

Therapeutic Plasma Exchange in Children With Severe Sepsis and Septic Shock: A Randomized Controlled Clinical Trial

The aim of the study will be to to evaluate whether therapeutic plasma exchange (TPE) reduces mortality in critically ill children with severe sepsis or septic shock compared to the standard care of sepsis alone.

The study population will be divided into two groups, the first group will receive standard sepsis management plus therapeutic plasma exchange and the second one will receive the standard sepsis management alone . Then we will assess the effect of TPE on : Severity of organ dysfunction (pSOFA score) , duration of vasopressor support , length of PICU stay, time to hemodynamic stabilization , and on inflammatory and coagulation biomarkers

This will be a Prospective, randomized, controlled, open- label, parallel-group, center clinical trial, which will be conducted on critically ill children with severe sepsis and septic shock, admitted into the Pediatric Intensive Care Unit (PICU) of Menoufia University Hospital from August 2026 to February 2027.

Eligible patients will be randomized using a computer-generated random sequence into:

1. - Intervention Group (plasma exchange Arm): Standard sepsis management plus therapeutic plasma exchange.
2. - Control Group (Standard care Arm): Standard sepsis management alone. Interventions

Standard Care (Both Groups):

1. - Early antimicrobial therapy

2. - Fluid resuscitation.

3. - Vasopressor and inotropic support

4. - Mechanical ventilation as indicated

5. - Organ support according to PICU protocols Therapeutic Plasma Exchange (TPE) Protocol

   • Initiation: Within 24 hours of diagnosis.
   • Frequency: Once daily for 1-5 sessions (Connelly et al.,2023)
   • Plasma Volume: 1-1.5 plasma volumes per session.
   • Replacement Fluid: Fresh frozen plasma (FFP).
   • Anticoagulation: Citrate or heparin according to institutional protocol.
   • Monitoring: Continuous hemodynamic and laboratory monitoring (All adverse events related to TPE (hypotension, bleeding, electrolyte disturbances, allergic reactions) will be recorded and managed according to PICU protocols.

All patients will be subjected to:

1. Demographic data will be collected from each participant, including age, sex, and weight, height, and body mass index.

2. Clinical Assessment:

   • Detailed history and physical examination.
   • Scoring of the severity of the disease using pSOFA (Pediatric Sequential Organ Failure Assessment) and PELOD-2 (Pediatric Logistic Organ Dysfunction 2) scores.

3. Laboratory investigations:

1) - Complete blood count (CBC). 2) - C-reactive protein (CRP). 3) - Procalcitonin (PCT). 4) - Coagulation profile (PT, aPTT and INR). 5) - Liver functions (ALT and AST). 6) - Kidney functions (Urea and creatinine). 7) - Electrolytes: Sodium (Na), potassium (K) and Calcium (Ca) levels. 8) - Serum lactate level and LDH. 9) - Blood cultures for all cases, urine and CSF culture (if indicated).

Inclusion Criteria:

1. From one month to 18 years.
2. With an established diagnosis of severe sepsis or septic shock according to international pediatric sepsis definitions.

Exclusion Criteria:

1. Known congenital bleeding disorders and severe uncontrolled hemorrhage.
2. End-stage chronic illness with expected survival < 3 months.
3. Previous plasma exchange during the same admission.
4. Contraindications to central venous catheterization.