Fluids and Antimicrobials and Pressors…. Oh My! Updates on the Management of Pediatric Sepsis
Myron Yaster, MD and Justin L. Lockman, MD, MSEd
In the Society for Pediatric Anesthesia’s Question of the week (12/10/2021), Osama Elazzouny, MD and Heather Byrd, MD of the Children’s Hospital of Georgia, Augusta, GA provided a neonatal sepsis/shock question and answer that I (MY) disagreed with. In the question, a 1-week old in the OR develops signs and symptoms of shock that didn’t respond to 60 mL of isotonic saline. The question of the week: What’s the next step? The authors’ answer (presuming septic shock): dopamine infusion of 5 MICROgrams/kg/min. While dopamine is a reasonable answer many of you may have chosen, my answer was to start a prostaglandin infusion (in case this was a duct-dependent lesion) and epinephrine as the first line vasopressor, not dopamine. To get a better sense of who was right, I checked SPA’s “source of truth” the PediCrisis App “Hypotension” checklist and emailed several of the PAAD’s editorial council as well. There was little support for my prostaglandin answer (although I still think that’s the right thing to do!) and there was a split on dopamine vs. epinephrine (or norepinephrine) as the first line agent. As a “tie breaker,” Justin Lockman (our PAAD critical care guru) provided the 2020 Pediatric Sepsis Guidelines by Weiss et al. This is a long article (70 + pages) that few of you have likely read, but it’s worth understanding what’s in it. So Justin and I will summarize some of the highlights today and encourage you to review the whole thing when you have time. Incidentally, Justin also agrees that it’s never wrong to start prostaglandins in a neonate less than a week of age in shock of unclear etiology. Myron Yaster, MD
Weiss SL, Peters MJ, Alhazzani W, Agus MSD, et al. Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. Pediatr Crit Care Med. 2020 Feb;21(2):e52-e106. PMID: 32032273
From the article: “Sepsis is a leading cause of morbidity, mortality, and healthcare utilization for children worldwide. Globally, an estimated 22 cases of childhood sepsis per 100,000 person-years and 2,202 cases of neonatal sepsis per 100,000 live births occur, translating into 1.2 million cases of childhood sepsis per year.” The majority of children who die of sepsis suffer from refractory shock and/or multiple organ dysfunction syndrome, with many deaths occurring within the initial 48 to 72 hours of treatment. Early identification and appropriate resuscitation and management are therefore critical to optimizing outcomes for children with sepsis.” Many of our perioperative patients will present with sepsis (as in the patient with an infected infusion port being removed for source control) or develop sepsis during surgery (as in those with a bowel perforation) – so it’s critical that anesthesiologists know how to handle these patients. Importantly, these guidelines are intended to apply to all children from the (full term) neonatal period through the teenage years, excluding preterm neonates.
Key findings/recommendations (with our commentary)
1. Blood lactate levels provide a valuable indirect marker of tissue hypoperfusion. Although increased lactate levels are not specific, they provide a quantifiable surrogate for tissue hypoxia and can be rapidly obtained by point-of-care tests available in many settings. In adults, blood lactate greater than 2 mmol/L is now included within the operational definition of septic shock. Even if lactate testing is not quickly available, unexplained metabolic acidosis in patients at risk for sepsis and without volume depletion should be assumed to be related to septic shock.
2. Obtain blood cultures before initiating antimicrobial therapy in situations where this does not substantially delay antimicrobial administration. While peripheral stick is ideal, blood cultures can be drawn from existing central lines or even arterial lines in some settings (follow your hospital’s local guidelines) and can help with narrowing therapy later.
3. In children with septic shock, start empiric broad-spectrum therapy (with one or more antimicrobials to cover all likely pathogens) within 1 hour of recognition.
a. Please see the article for specific antibiotic and antifungal recommendations; local custom/resistance patterns are also relevant, so consult hospital resources if you need help with choosing medications.
4. Remove sources of ongoing infection such as I&D of abscess, infected central lines, empyema drainage etc. Particularly in children, this often means they will require general anesthesia while in septic shock.
5. Fluid therapy
a. Rapid administration of balanced, buffered crystalloids solutions such as PlasmaLyte or Ringers Lactate (not albumin or synthetic colloids [e.g. Hetastarch] or normal saline), 40-60 mL/kg in 10-20 mL/kg boluses. Fluids should be given rapidly via IV or IO. If no IV after 90 seconds, do not hesitate to place IO access. Consider normal saline in patients with increased intracranial pressure or with hyponatremia.
b. The guidelines suggest against transfusion of RBCs if the blood hemoglobin concentration is greater than or equal to 7 g/dL in hemodynamically stabilized children with septic shock or other sepsis-associated organ dysfunction. Note that this recommendation is based on non-bleeding patients; as with all trauma patients, our surgical patients may require blood with higher hemoglobin values.
c. The guidelines suggest against prophylactic platelet transfusion based solely on platelet levels in nonbleeding children with septic shock or other sepsis-associated organ dysfunction and thrombocytopenia.r sepsis-associated organ dysfunction and thrombocytopenia.
6. Guidelines about the use of vasoactive medications
First, the elephant in the room: many neonatologists love dopamine and convincing them to stop using it, is, or will be, nearly impossible. They have decades of experience showing it is safe in neonates with transitional hypotension. That said, a few things to consider as you review these guidelines. First, neonatologists were on the panel that developed the guidelines. Second we must acknowledge that transitional hypotension and (later) sepsis are two different entities with different pathophysiologies. Finally, the primary reason for dopamine in neonates is based on a perception of lower risk of intraventricular hemorrhage compared to epinephrine. However, this is based on preemie concerns/IVH risk, and in fact a small study (1) in neonates comparing dopa to epi showed improved hemodynamic stability among preemies in the epi group with no difference in adverse events. For a separate review article on neonatal sepsis, see this article.(2) Ok, so here are the recommendations:
a. Use epinephrine, rather than dopamine
b. Use norepinephrine, rather than dopamine
c. Vasoactive drugs can be given through a peripheral IV or IO until central access is obtained. This is not a safe long-term plan so if vasoactives are started, consider placement of a central venous line so that peripheral administration can stop as soon as possible (hours not days).
d. If high dose catecholamines are ineffective, consider adding vasopressin
e. There is little evidence to support inodilators (including milrinone, dobutamine, and levosimendan) even though most people will use them in the PICU for children with refractory poor perfusion.
a. As anesthesiologists, we are often consulted to help with both intubation and ventilation. Do not use etomidate to facilitate intubation in septic patients because it depresses adrenal function (FDA black box warning).
b. Use PEEP to prevent alveolar collapse, restore end-expiratory lung volume, and improve mean airway pressures, all of which help to improve adequate oxygenation in PARDS patients and minimize unnecessary use of high FiO2.
c. Consider a trial of prone positioning in children with sepsis and severe pediatric ARDS (particularly with significant hypoxemia). Despite the complexity involved in proning critically-ill patients, this has been shown to recruit areas of collapsed, de-recruited lung with resultant improved elastance, decreased lung stress and strain, and improved functional residual capacity.
d. Consider neuromuscular blockade. This is mostly relevant in the ICU, as many surgical patients receive neuromuscular blocking agents anyway, but for those who are not, remember that neuromuscular blockade can improve ventilator synchrony, oxygenation, and ventilation.
One final recommendation about ventilation (from our experience): children with severe metabolic acidosis will often hyperventilate themselves to a PCO2 of 20 or even lower in order to keep their pH above 7. When we intubate them, if we ventilate “normally” to a PCO2 of 40, this causes a profound drop in pH and sometimes cardiac arrest. So be sure to match what they are doing and follow blood gases.
In summary, give balanced crystalloid, give antimicrobials (after drawing blood cultures if there is time), and start vasopressors (epinephrine or norepinephrine). And of course, recognizing that you need help and calling your PICU colleagues to help with management of critically-ill children is a sign of strength, not of weakness.
Happy Holidays, all! We will be going on Christmas- New Year’s break so we’ll see you in the New Year!
Myron Yaster, MD and Justin L. Lockman, MD, MSEd
Baske, K., Saini, S. S., Dutta, S. & Sundaram, V. Epinephrine versus dopamine in neonatal septic shock: a double-blind randomized controlled trial. Eur. J. Pediatr.177, 1335–1342 (2018). PMID: 29936590
Kharrat A., Jain A. Hemodynamic dysfunction in neonatal sepsis. Pediatric Research (online ahead of print). November 2021. PMID: 34819654