Surviving Sepsis: Pediatric Style

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The Pre-brief

A simple, practical case to start: 

An 18-month-old infant with a 4 day history of vomiting and fever is brought to the ER by his mother. He is lethargic and poorly responsive. Temp 101F, HR 200bpm, BP 70/30mmHg, RR 50rpm with clear breath sounds and SaO2 94%, cool extremities, capillary refill time 5 seconds.

A few notes here…

It’s important to remember that kids have an enhanced ability to compensate in shock – thus, hypotension is a LATE and serious sign. Septic shock more often presents with low cardiac output and high systemic vascular resistance (often referred to as “cold shock”).

Neonates, in particular, cannot increase stroke volume very much. Therefore, to maintain their cardiac output (CO = HR x SV), they are very HR dependent.

This year the Surviving Sepsis Campaign published guidelines custom-made for pediatrics!

The Down and Dirty

For a child in septic shock the following must be done quickly:

  1. Obtain IV/IO access.
  2. Collect blood culture – if difficult to obtain, move quickly to step 3.
  3. Start empiric broad-spectrum antibiotics (table 1).
  4. Measure lactate.
  5. Administer fluid boluses 10-20ml/kg IF shock present and the patient doesn’t otherwise have evidence of fluid. *Repeat this step and consider additional boluses of 10-20ml/kg until shock resolves or signs of fluid overload develop.
  6. Start vasoactive medications if shock persists after step 5.

Table 1: Empiric Drug Dosing Tailored to Pediatric Sepsis

Infants (<=28 days) 
<7 days, no meningitisAmpicillin + Gentamicin (dosing varies)
<7 days, meningitisAmpicillin + Cefepime (dosing varies)
8 – 28 daysAmpicillin (dosing varies) + Ceftriaxone (75mg/kg IV qDay)
Concern for HSV infectionADD Acyclovir (dosing varies)
Children (>28 days) 
No meningitisCeftriaxone (75mg/kg IV qDay, max 2g/day) 
MeningitisCeftriaxone (50mg/kg IV q12h, max 4g/day) + Vancomycin (15-20mg/kg q8h-q6h depending on age and indication) 
Concern for GI source

CHANGE Ceftriaxone to Piperacillin-Tazobactam (200-400mg/kg/day IV divided q8h-q6h) or extended infusion

OR

ADD Metronidazole 10mg/kg IV q8h-q6h, max 500mg/dose) OR Clindamycin (10mg/kg q8h, max 600mg/dose)

Renal dysfunctionConsider dose adjustment for: Acyclovir, Cefepime, Vancomycin, and Piperacillin-Tazobactam

Always confirm dosing and frequency with your hospital pharmacist.

Timeless or trend-driven?

The consensus recommendations for pediatric sepsis are summarized in 77 statements. Of these, only SIX recommendations were STRONG. There is clearly LOTS to learn in pediatric sepsis, which is one reason that as a pediatric intensivist, I appreciate the adult literature on this topic. However, it’s important for adult and pediatric intensivists alike – to know the nuances about treating sepsis in children.

For the most part the pediatric guidelines are classic, conservative, and similar to adult guidelines. The differences, along with overall highlights from the pediatric guidelines, can be found in table 2.

Table 2: Refined guidelines in pediatrics as compared to adults.1,2
  Highlights Pediatric Guidelines Differing From Adults
SCREENING, DIAGNOSIS, AND SYSTEMATIC MANAGEMENT Systematic screening and protocol implementation for identifying sepsis are recommended. No guidelines to use blood lactate levels to stratify children into risk groups. Smaller fluid boluses recommended, not driven by lactate.
ANTIMICROBIAL THERAPY Obtain blood cultures before initiating antibiotics, but do not delay starting empiric broad-spectrum antibiotics (within 1 hour of recognition of shock, or within 3 hours of sepsis without shock), narrow when pathogen identified.  
FLUID THERAPY 40-60ml/kg (10-20ml/kg aliquots) over the 1st hour.  Balanced crystalloids recommended over 0.9% saline. Discontinue if signs of fluid overload develop.  Albumin not recommended. Guidelines for healthcare systems without PICU availability fluid boluses not recommended in the absence of hypotension. Balanced/buffered crystalloids recommended over 0.9% saline or albumin for fluid resuscitation.
HEMODYNAMIC MONITORING Use trends in lactate levels and clinical assessment to guide resuscitation. It’s not a direct measure of tissue perfusion, but increased lactate is associated with worse outcomes in kids. No clear guidance on blood pressure target.  
VASOACTIVE MEDICATIONS 1st line – epinephrine or norepinephrine. Next – vasopressin. No preference for 1st line agent between epinephrine and norepinephrine. Consider epinephrine for myocardial dysfunction. Norepinephrine and epinephrine preferred over dopamineb. No mention of dobutamine.
VENTILATION Consider trial of NIV with CPAP/BiPAP.  If intubated for sepsis + pediatric acute respiratory distress syndrome, use high PEEP, trial prone positioning, use iNO as rescue therapy, and use paralysis. Consider noninvasive ventilation if clinically appropriate. No recommendation against HFOV.
CORTICOSTEROIDS You can try IV hydrocortisone but definitely recommended if fluids and vasopressors don’t restore hemodynamics.  
ENDOCRINE AND METABOLIC No specific recommendation for glucose calcium levels. Adult guidelines recommend keeping blood glucose <180mg/dL.
NUTRITION No recommendation, but preference to start gastric enteral nutrition (not post-pyloric) within 48 hours if no contraindications. Parenteral nutrition (TPN) may be withheld for 7 days. Against prokinetic agents for feeding intolerance. Against vitamin C and thiamine (not mentioned in the adult guidelines either but there’s a lot of adult literature on the subject).
BLOOD PRODUCTS Don’t transfuse if hemoglobin is >=7g/dL in hemodynamically stable kids. No recommendation for unstable shock.  
RRT, ECMO Recommend RRT to prevent fluid overload.  VV ECMO for sepsis-induced PARDS and refractory hypoxia.  VA ECMO for refractory shock.  
IMMUNOGLOBULINS Against routine use of IVIG.  
PROPHYLAXIS Against ROUTINE use of stress ulcer and DVT prophylaxis. Gastric prophylaxis only in HIGH risk populations. DVT prophylaxis not recommended.
Dopamine has been associated with an increased risk of death and healthcare-associated infection.3

The Debrief

Let’s get the case polished off:

The child is determined to be in septic shock. 40ml/kg of lactated ringers is administered in 20ml/kg aliquots. The first bolus of fluid briefly improved the blood pressure, but it subsequently fell and the 2nd aliquot was not beneficial. While fluids were being administered, zosyn was initiated and labs were sent including a comprehensive metabolic panel, complete blood count, blood gas, coagulation studies, type and screen, and blood culture. Central venous access was established and epinephrine was started at 0.05mcg/kg/min and titrated to an appropriate blood pressure for age. The child was then transferred to the PICU for continued management.

Check out: the Surviving Sepsis Campaign’s Pediatric Sepsis Guidelines for more about these modern recommendations on how to treat sepsis – pediatric style!

References

  1. Weiss SL, Peters MJ, Alhazzani W, et al. Executive Summary: Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children, Pediatric Critical Care Medicine: February 2020 – Volume 21 – Issue 2 – p 186-195 doi: 10.1097/PCC.0000000000002197. PMID: 32032264.
  2. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016, Critical Care Medicine: March 2017 – Volume 45 – Issue 3 – p 486-552 doi: 10.1097/CCM.0000000000002255. PMID: 28101605.
  3. Ventura AM, Shieh HH, Bousso A, et al. Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock. Crit Care Med. 2015 Nov;43(11):2292-302. doi: 10.1097/CCM.0000000000001260. PMID: 26323041.
  4.  

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