Plasma Exchange in Children With Severe Sepsis and Septic Shock

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).

• Plasma exchange (PE) (Procedure): Therapeutic plasma exchange to the intervention Group (plasma exchange Arm) that will receive also the standard sepsis management.

Primary outcomes

• Primary Outcome Measure [28 days]: All-cause mortality within 28 days after randomization, defined as the proportion of participants who die from any cause within 28 days of enrollment.

Secondary outcomes

• Change in pediatric Sequential Organ Failure Assessment (pSOFA) score [Baseline, Day 1, Day 3, and Day 7]: Change in pSOFA score from baseline measured on days 1, 3, and 7 after randomization.
• Duration of vasopressor support [Up to 28 days]: Number of days participants require vasopressor support after randomization.
• Length of pediatric intensive care unit (PICU) stay [Up to 28 days]: Number of days participants remain admitted to the PICU.
• Time to shock resolution [Up to 28 days]: Time from randomization until resolution of septic shock
• Change in C-reactive protein (CRP) [Baseline, Day 3, and Day 7]: Change in serum CRP concentration from baseline.
• Change in procalcitonin concentration [Baseline, Day 3, and Day 7]: Change in serum procalcitonin concentration from baseline.
• Platelet count [Baseline, Day 3, and Day 7]: Change in platelet count from baseline.
• International normalized ratio (INR) [Baseline, Day 3, and Day 7]: Change in INR from baseline.
• Fibrinogen concentration [Baseline, Day 3, and Day 7]: Change in plasma fibrinogen concentration from baseline.
• Incidence of therapeutic plasma exchange-related adverse events [Up to 28 days]: Number of participants experiencing adverse events related to therapeutic plasma exchange.

Sex: All, ages: 1 Month to 18 Years

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.

• Hani Hamed Saad, MD, pediatrics, Principal investigator, Faculty of medicine, Menoufia University