One-liner…
What’s the rationale for continuous renal replacement therapy (CRRT) in paediatric sepsis, and what’s the evidence-based expert consensus guidance?
A previously fit and well 5-year-old, Maya, presents to your DGH A&E with fever and cough. Mum tells you she isn’t herself, and the triage nurse calls you in to assess her urgently.
You walk in, see that she looks very unwell and perform an A to E assessment as below:
A: Patent
B: SpO2 85% in air; 98% in 15L; tachypnoeic, recessing, grunting, reduced AE on R side
C: Tachycardic, CRT 3-4s centrally, 5s peripherally, unable to get a BP, lactate 6 on cap gas
D: GCS 14/15, she looks tired and mum says she seems agitated at times
E: T39.4, no rashes, abdomen soft
F: Na 130 on gas, has PU only once today
You ask the nursing team to start 2L/kg/min HFNC oxygen while you cannulate her and take bloods and cultures, asking the ED SHO to update your consultant and prescribe IV Ceftriaxone in the meantime.
You administer 10ml/kg fluid boluses, reassessing as you go, and give a total of 30ml/kg while waiting for your consultant to arrive, noting that her HR and lactate improve slightly but the response is short-lasting.
Background
Sepsis and septic shock are common presentations to Paediatric A&E. A recent post-pandemic surge in invasive Group A strep (iGAS) infections led to many critically unwell children requiring admission to PICU for multiorgan support.
CRRT is a useful adjuvant in the management of paediatric sepsis and is thought to be especially useful when a known toxin is released, such as the bacterial exotoxins of iGAS.
Maya’s CRP comes back >300, and the urgent CXR you requested shows a complete white-out on the right side. Your consultant arrives and asks you to call the retrieval team, while she liaises with the Anaesthetic team for review, as she’s worried about septic shock and potential decompensation.
Maya is accepted for transfer to PICU, and the Anaesthetic team prepares to intubate. She becomes hypotensive, requiring a 4th fluid bolus, and you commence peripheral noradrenaline whilst waiting for the retrieval team. When they arrive, they take handover, insert a central line and start infusions of noradrenaline and adrenaline before leaving with Maya.
How do you define sepsis and septic shock?
The Phoenix Sepsis criteria are an updated international paediatric sepsis scoring system that replaces the previous SIRS-based scoring system. The Phoenix Sepsis Score uses criteria assessing cardiovascular, respiratory, neurological, and coagulation functions to provide a composite score.
The Phoenix Sepsis Score can be used in term neonates (37/40 onwards) up until their 18th birthday. A score of ≥2 points, along with suspected infection, is defined as sepsis; sepsis plus ≥1 cardiovascular point meets the threshold for septic shock.
The next morning, your lab calls you saying that the blood culture you took has grown Group A Strep. You phone this through to the receiving PICU and ask for an update on Maya, and discover that she has deteriorated further.
She is ventilated with a right-sided chest drain draining frank pus, and requires multiple vasoactive medications to maintain target MAPs.
Her CRP has improved slightly, but her WCC has doubled, and she has been started on Clindamycin. IVIG is also being considered for the treatment of Streptococcal Toxic Shock Syndrome. She also has an AKI and has been started on CRRT.
The PICU fellow mentions iGAS was one of their top differentials and thanks you for confirming the results.
When does GAS become invasive?
Group A Strep is defined as iGAS when Streptococcus pyogenes is cultured from a normally sterile site.
In ~10% of iGAS cases, virulence factors lead to superantigen toxin production, causing T-cell overstimulation and toxic shock syndrome. Reported cases may have a mortality rate similar to, or even higher than, that seen in invasive meningococcal disease. The most severe and life-threatening presentations of iGAS include STSS and necrotising fasciitis.
How do you define Paediatric AKI?
Paediatric AKI is an abrupt rise in serum creatinine and a decrease in urine output, reflecting injury to the kidney tubular epithelium.
Serum creatinine alone is not a reliable marker of AKI severity. Its concentration is influenced by factors such as age, sex, muscle mass, and volume status, and it may not peak until up to 72 hours after the initial insult.
Several paediatric scoring systems are used to stage the severity of AKI, including pRIFLE, AKIN, and KDIGO.
Greater AKI severity is associated with increased morbidity and mortality. Prognosis is closely linked to the underlying aetiology, with sepsis-induced AKI and fluid overload both identified as independent risk factors for death.
Previous research has shown higher mortality in children with fluid overload in PICU, with some studies reporting a 3% increase in mortality for every 1% rise in fluid overload.
Renal replacement therapy is increasingly used to manage fluid status. It can also help correct metabolic and electrolyte disturbances and may have additional immunomodulatory effects.
What is CRRT?
It is a form of continuous haemofiltration that uses an extracorporeal circuit to mimic kidney function. It may be initiated for both renal and non-renal indications and has been used to treat refractory hyperkalaemia, metabolic acidosis, fluid overload, poisoning, and symptomatic uraemia.
Because it is a continuous process, CRRT is better tolerated than intermittent haemodialysis, thereby enabling its use in haemodynamically unstable patients, such as those with sepsis.
How does CRRT work?
CRRT is thought to work through several mechanisms. It targets key aspects of the disease process, including post-resuscitation fluid overload, AKI, and electrolyte imbalances, while also correcting coagulopathy and buffering metabolic acidosis.
The process of ultrafiltration may also assist in sepsis by continually removing proinflammatory mediators and toxins, such as those released during iGAS, that lead to subsequent cytokine storm, thereby potentiating multiorgan dysfunction.
It also enables the delivery of optimal critical care by managing fluid balance, thereby permitting adequate nutrition and the administration of fluid volumes associated with treatments such as IVIG, antimicrobials, and blood products.
Are there any risks to CRRT?
In short, yes! It’s easiest to think of these in relation to each component of CRRT.
VasCath-related complications, e.g. bleeding, thrombosis, infection, failure of insertion, dislodgement
Circuit-related complications, e.g. fluid shifts on commencement, haemodynamic instability, DIC, thrombocytopenia, hypothermia, electrolyte disturbances, air emboli, circuit clotting, inadequate flow rates, altered drug pharmacokinetics and the need for drug dose adjustment
Anticoagulation-related complications, e.g. bleeding, potential for citrate accumulation and further derangement of electrolytes, including calcium
The evidence
There is currently minimal high-quality evidence favouring the use of CRRT in paediatric sepsis. The rationale for its use has been extrapolated from limited studies within adult populations.
There is currently no clear evidence to define the optimal timing for initiating CRRT. However, earlier initiation is thought to be associated with more favourable outcomes, which is consistent with the established link between fluid overload and increased mortality.
Ultimately, expert consensus guidance from the Surviving Sepsis Campaign acknowledges the potential benefits of CRRT in sepsis and septic shock. However, it recommends its use only after an inadequate response to conservative strategies such as fluid restriction and/or diuresis. Notably, the 49 international experts involved in the guideline emphasise that using CRRT to prevent or treat fluid overload is a weak recommendation based on very low-quality evidence.
A few weeks later, you receive an email from your consultant informing you that Maya has been discharged from PICU to the general ward.
She asks if you would like to see Maya with her in the AKI clinic next month and thanks the team for their hard work and rapid recognition of septic shock the night she presented.
Take-homes
CRRT is traditionally used to treat fluid overload causing respiratory compromise, hyperkalaemia, symptomatic uraemia and metabolic acidosis
In sepsis, it can help prevent and treat fluid overload from initial resuscitation and then AKI, as well as allowing volume-rich treatments on PICU, e.g. nutrition, IVIG, blood products, etc
Ultrafiltration of proinflammatory mediators and toxins might help prevent some of the cytokine storm that causes multiorgan dysfunction in sepsis (though it might also filter out beneficial mediators!).
There’s no consensus on exactly when to start CRRT in sepsis, but early initiation may be better to reduce fluid overload, which is associated with increased mortality on the PICU
About PICSTAR
PICSTAR is a trainee-led research network open to all doctors, nurses and allied health trainees within Paediatric Intensive Care. We are the trainee arm of the Paediatric Critical Care Society – Study Group (PCCS-SG) and work with them on research, audit and service evaluation.
If you would like to join PICSTAR and get involved in projects, have ideas you would like to propose or get advice/mentorship via PCCS-SG, don’t hesitate to contact us at picstar.network@gmail.com. See their website for more: https://pccsociety.uk/research/picstar/
References
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