The ABCs of Pediatric Sepsis

On January 29, 2007, 14-year-old Andrew John McDonough was brought to the hospital for what his parents thought was appendicitis. Andrew was a healthy teenager who, earlier that week, had attended his high school dance, gone skiing and, less than 48 hours before his illness, helped his team win the Pennsylvania state soccer championship.¹

Andrew did not have appendicitis. In the hospital his parents were told he had been diagnosed with leukemia and, before the day was out, Andrew had gone into cardiac arrest due to septic shock.

While leukemia was a terrible but familiar word, Andrew’s parents did not understand what “septic shock” was and how it could have hit Andrew so fast and so hard.

The Most Common Deadly Disease You’ve Never Heard Of

Globally, 6 million children die every year from sepsis.² In the United States more than 750,000 cases of adult and pediatric sepsis are diagnosed each year.^3–6 Incidence of sepsis in pediatric patients has been rising in the past decades, growing to more than 75,000 hospitalizations for severe sepsis, with a mortality of greater than 10%, at a cost of $4.8 billion dollars.^7–9

So why is pediatric sepsis the most common deadly disease you’ve never heard of? Even among advanced healthcare providers, understanding and documentation of sepsis as a primary disease are poor. Many EMS providers think sepsis is a rarely encountered and slowly progressing disease found in elderly patients. The truth is that sepsis is terribly common, affects all age groups and in pediatric patients, is often subtle, with deterioration occurring suddenly and fatally.¹⁰

EMS Can Make the Difference

While sepsis accounts for approximately one in five ICU admissions, it is not just an “in-hospital” problem.¹¹ Not only does EMS see sepsis often, these patients are some of our sickest.¹² In 2010 the EMS system in King County, WA, found an incidence rate of sepsis of 3.3%, yet the incidence rate for MI was only 2.3% and for stroke only 2.2%.¹³

Studies have shown that when EMS transports sepsis patients, these patients receive IV fluids, antibiotics and in-hospital sepsis treatment much faster.^14,15 Likewise, systems with designated sepsis alerts are shown to reduce overall sepsis mortality along with significant reductions in length of hospital stay, time in ICU and cost per stay.^16,17

Unfortunately the research also shows that many EMS systems have a long way to go when it comes to identifying sepsis. One study showed that despite significant abnormalities in the vital signs of septic patients (25% had systolic BP <90 mmHg), serial vital signs were often not taken or were poorly documented, only 38% had an IV line started with average fluid delivered of 300ml, and cardiac monitoring was performed less than 50% of the time.¹³

Is it that we don’t care, or that we don’t know? A 2013 study evaluated over 200 EMS providers, 83% of whom were paramedics and 73% of whom had been in EMS for over 10 years. They were given four scenarios in which to identify septic shock. Only 10% of them got the scenarios correct.¹⁸

Something that may help EMS providers move forward is the recently released Washington Consensus Conference definition and clinical criteria for sepsis—also known as SEPSIS III— published in JAMA [Singer, M. et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315, 801–810 (2016).] The hope is that this newly revised definition will help put more providers on the same page when it comes to sepsis. For now though, SEPSIS III applies only to adult patients leaving many

EMS providers may wonder where to begin with pediatric patients. Fortunately the answer follows a format that most EMS providers already know. To help victims of sepsis overall and pediatric patients specifically, EMS providers can follow the ABCs:

• Acquire knowledge about sepsis;
• Be ready to give sepsis alerts;
• Children with sepsis need an advocate.

To start acquiring knowledge about sepsis, we can use another set of ABCs to describe the pathology: the patient acquires infection, blood vessel problems develop, leading to circulatory collapse.

Acquire Infection

Sepsis always begins with some kind of infection. Bacterial, viral, parasitic or fungal pathogens get inside the body and begin to reproduce in the area of infection. These pathogens release toxins called exotoxins and endotoxins that damage the local body tissue. Normally the body’s first line of defense—the innate immune response—senses these toxins and begins to act quickly to attack the pathogens producing them.¹⁹

The immune system’s first responders are local macrophages (“eating” white blood cells) that attempt to consume and destroy the pathogens. During this process macrophages release a variety of cytokines (cell signaling proteins) that activate additional immune responses to battle pathogens.

Among other actions, these cytokines trigger inflammation in the area of infection that causes blood vessels to dilate, capillaries to leak and tissue edema, all of which allow greater flow of immune responders into the area to attack pathogens.²⁰ Neutrophils (“fighting” white blood cells) and other immune factors respond to the area of infection to fight pathogens, harming some “good” body tissue along the way.¹⁹ This damage can result in even more blood vessel leakage and release of more cytokine signaling chemicals. Cytokines may now cause a temperature increase in the infected tissues and ultimately cue the hypothalamus to reset the patient’s body temperature, which produces a fever.²⁰

These temperature increases are a good thing as they help to both slow pathogen replication and improve immune system activation. Signaling chemicals also trigger increased clotting and decreased fibrinolysis (anti-clotting), causing the neutrophils, macrophages and other material to clump against blood vessel walls.²⁰

All of these physiological responses have intrinsic limits and antagonistic factors to help the body rapidly restore balance once the danger has passed. When the local infection has been overcome, the body will immediately begin to deactivate the response, repair the damage and clean up the debris to restore normal function to the previously infected area.¹⁹

Blood Vessel Problems

Systemic Inflammatory Response Syndrome (SIRS) and Sepsis

Cytokines sometimes travel beyond the area of initial infection. This can trigger a domino effect of inflammation, immune response and coagulation that may allow the infection to journey throughout the body thanks to the dilated, leaky and damaged vessels that are now present in response to the overwhelming infection.²⁰

As the infection and accompanying inflammatory, immune and coagulation responses spread, a condition known as Systemic Inflammatory Response Syndrome, or SIRS, occurs. While other events such as trauma, pancreatitis, pulmonary embolism and anaphylaxis can also trigger SIRS, when SIRS is caused by an infection it is called sepsis. Sepsis is a result of the cytokines spreading throughout the body triggering vasodilation (causing distributive shock) and leaky blood vessels (causing hypovolemic shock), and causing many smaller blood vessels to be blocked by clots (causing obstructive shock) all at the same time.²¹

The clinical definition of SIRS22 is:

• Body temperature: >100.4 or <96.8
• White cell count: >12,000/mm3 or <4,000/mm3 or >10% band cells
• Tachycardia: HR >90 bpm
• Tachypnea: RR >20 bpm

While these criteria are not specific to pediatric patients (little hearts commonly beat faster than 90 bpm), by using a slightly modified version of this definition, we arrive at criteria that, when used by EMS providers, has been shown to have a sensitivity of 75%, versus providers attempting to identify sepsis without using specific criteria and only finding 12%.²³

Under this pediatric-modified sepsis criteria, a patient is considered septic if any two of the following are met:

• Body temperature: >100.4 or <96.8
• Altered mental status
• Tachycardia: HR >90 bpm or high for age range
• Tachypnea: RR >20 bpm or high for age range
• Serum glucose: <120 mg/dL (some protocols replace this with serum lactate >4 mmol/L)

One may think of an analogy between sepsis and anaphylaxis. If someone has an anaphylactic reaction to a bee sting, it isn’t the dose of honeybee toxin that’s going to kill them, it’s their body’s exaggerated immune response to that toxin. Sepsis is similar. The infection’s toxins will certainly do damage, but sepsis only occurs when the body’s reaction starts to go haywire and causes SIRS.

As if sepsis wasn’t challenging enough to deal with, the disruption of the inflammation, immune and clotting responses can lead to these systems being reversed or even shut down so that the body may not be able to mount an effective immune response or clot properly.^20,21,24 This will often allow the infection to gain even further ground, accelerating the downward spiral.

This complex interaction of inflammation, immune and clotting pathologies can leave providers feeling, Something is wrong with this child, but I don’t know what. It can be helpful to take a step back and remember that, simply, infection + sick = sepsis, as the body is forced to compensate for the shock, but no real dysfunction has yet occurred.

Yet while sepsis is bad, septic shock is far worse.

Circulatory Collapse

Septic Shock and Multiorgan Dysfunction Syndrome (MODS)

As the patient progresses down the sepsis spiral, at some point the body will no longer be able to compensate without assistance. This is when organ dysfunction begins and is the beginning of septic shock. At this point the body may respond well to supportive treatment such as an initial (of possibly many) fluid bolus of 20cc/kg.

When two or more of the body’s organ systems are impacted it is called multiorgan dysfunction syndrome, or MODS.²² The most critical organ systems are, of course, the cardiac and respiratory systems, but many other systems can begin to fail.^25,26 These systems include the kidneys, liver, GI tract and even the nervous system.²⁷ While the exact timing varies from patient to patient, when severe sepsis progresses far enough that it does not respond to fluid administration, multiorgan dysfunction syndrome is likely and we arrive at septic shock.^28,29

The clinical definition of MODS is:

• Systolic BP <90
• Mean arterial pressure (MAP) <65
• Acute Respiratory Distress Syndrome (ARDS)
• EtCO2 <32
• Glucose <120
• Lactate >4 mmol (Note: Many definitions and protocols use lactate, but it is important to remember that pediatric patients may have normal lactate levels despite being in severe sepsis or septic shock).

When the patient doesn’t respond to >60 cc/kg of fluids, septic shock is a very difficult and dire situation in adults. In pediatric patients, it is even worse.²²

Sepsis in Pediatric Patients

Neonatal Sepsis

Between 1995 and 2005, the prevalence of severe sepsis in newborns in the U.S. more than doubled, from 4.52 to 9.7 cases per 1,000 births.⁹  

While definitions vary, sepsis that develops within the first 72 hours of birth is generally considered early-onset neonatal sepsis, while sepsis that develops more than 72 hours, but up to as many as 30 days after birth, is considered late-onset neonatal sepsis.

When you look to identify if your patient may have an acquired infection consider the following neonatal risk factors:

• Premature birth;
• Mother’s water breaks >24 hours early;
• Mother has any of the following common infections untreated at the time of delivery: group B strep, syphilis, herpes, rubella, cytomegalovirus (CMV), toxoplasmosis.³⁰

Keep in mind that any child less than 90 days old is already at particular risk as their immune systems are not yet fully developed and they are incapable of making many of the antibodies necessary to protect themselves.

Sepsis in Infants

Incidence of pediatric severe sepsis is highest among infants (5.16 per 1,000), with the rate falling in older children (0.20 per 1,000 in 10 to 14 year olds). The rate in boys is 15% higher than in girls.⁷ When faced with a sick infant, consider any of the infections listed above when looking to identify possible acquired infection, plus respiratory synctial virus (RSV), E. Coli, listeria monocytogenes and meningitis.

Sepsis in Children

Niranjan “Tex” Kissoon, MD, FRCP(C), FAAP, MCCM, FACPE, vice president of medical affairs at BC Children’s Hospital and Sunny Hill Health Center in Canada, says that prehospital healthcare providers don’t need blood tests or pediatric critical care specialists to begin to identify and treat sepsis in children.

He stresses the importance of looking for signs early on and not waiting until a child is obviously crashing. “Providers have to have the mind-set that if the kid already looks sick, the danger signs are already there,” he says.³¹

He says that this medical truth has been known for so long that he quotes Macchiavelli on the subject: “The physicians say it happens in hectic fever, that in the beginning of the malady it is easy to cure but difficult to detect, but in the course of time, not having been either detected or treated in the beginning, it becomes easy to detect but difficult to cure.”³²

What Can EMS Do On A Call?

To manage pediatric sepsis EMS providers can follow the progression of sepsis pathology to identify, assess and treat sepsis:

• Acquired infection? Ask about infection history;
• Blood vessel problems? Assessment and sepsis alert criteria;
• Circulatory collapse? Aggressively treat severe sepsis and septic shock.

Acquired Infection? Check Their History

Pediatric patients should be assessed using the Pediatric Assessment Triangle (see Figure 1) to identify and begin treatment of immediate life threats.³³

The first step in recognizing sepsis is attempting to identify if the patient has an infection. Sometimes it will be obvious if a child has an infection, but many times the signs of the infection will be subtle.³⁴

Consider the following clues and cues for infection: Is the child either febrile or hypothermic (possible in circulatory collapse: severe sepsis and septic shock)? Does the child have a recent history of vomiting or diarrhea? Burns? Abscesses? Blotches? Have they recently been on antibiotics? Have they had regular childhood immunizations withheld?

Immunocompromised children are at high risk for sepsis. Is the child on immunotherapy, chemotherapy, steroid administration or other therapy that will decrease or disrupt their immune response?

Medical history or comorbidities that put pediatric patients at risk for sepsis include:³⁵

• Acquired Immune Deficiency Syndrome (AIDS)
• Developmental delay
• Sickle cell disease
• Cystic fibrosis
• Cancer
• Premature birth
• Poor respiratory function
• Poor cardiac reserves
• Liver or splenic dysfunction
• Recent surgery
• Indwelling devices
• Transplant organs
• Any B or T cell deficiency.

Remember that not every infection a child gets will lead to sepsis, nor will a definite diagnosis of sepsis mean that the patient cannot have other medical problems that EMS may also need to treat.³⁵

Blood Vessel Problems? Assessment and Sepsis Alert Criteria

If you believe your young patient has an infection, the question you should ask yourself is, “Is this patient hypoperfusing?”

Different assessment tools, techniques and checklists are available to providers in different systems, but signs of pediatric hypoperfusion include the following:^28,36–39

• Altered mental status (GCS <12 or a change >3)
• Significantly increased or decreased pulse rate for age
• Significantly decreased blood pressure for age (late sign)
• Mean arterial pressure (MAP) <65
• Difference between central and peripheral pulses
• SpO2 <94%
• etCO2 <32
• Temperature >100.0 or <96.0
• Glucometry >180 mg/dl
• Lactate >4 mmol/L
• Ultrasound shows IVC decreases in diameter >50% on inspiration
• Urine output <1 ml/kg/hr (dry diapers).

EMS sepsis alerts have been shown to significantly decrease time to treatment for sepsis patients and reduce mortality rates. However, even if you don’t currently work in a system that uses sepsis alerts, knowing the criteria will help you better recognize pediatric victims of sepsis, allowing you to make better clinical decisions and be a better patient advocate.^40,41 While many system-specific adult and pediatric sepsis alert criteria are available—some simple and some complex—it is critical for EMS providers to understand that not having a local alert protocol does not mean there is nothing you can do.

While defined sepsis alerts are helpful, there are ways every EMS provider can make a difference for pediatric sepsis patients even if their system does not currently use specific sepsis alert criteria. If you have identified a pediatric patient with an acquired infection who has blood vessel problems (shock) you can still make a tremendous difference for your patient by simply telling the emergency department staff, “I suspect sepsis.”⁴²

Circulatory Collapse? Rapidly And Aggressively Treat Septic Shock

When evidence (or strong suspicion) of acquired infection is accompanied by findings of cardiovascular dysfunction such as systolic BP <100 after administration of a 20cc/kg fluid bolus, acute respiratory distress syndrome (ARDS), or two or more other organ dysfunctions, it is considered septic shock.²²

If the patient is allowed to move further down the sepsis spiral without intervention, multiorgan dysfunction syndrome (MODS) is likely to begin.

Treatment

The biggest challenge is making sure you recognize your pediatric patient is suffering from sepsis in the first place. Once that has been accomplished, treatment follows the typical ABCD (airway, breathing, circulation, drugs) pathway, along with activation of a sepsis alert and a good patient hand-off with advocacy.

Airway
Pediatric patients experiencing severe sepsis or septic shock may require placement of an advanced airway. While rapid sequence intubation or med-facilitated intubation may be appropriate, it is important that advanced providers do not use etomidate on septic pediatric patients. Etomidate inhibits 11-β-hydroxylase, an enzyme necessary for cortisol production. This can block the body’s normal stress response and increase the severity of septic illness.^43,44

Breathing

The primary goals are to reduce the work of breathing and increase oxygenation for your pediatric patient. A distressed pediatric patient will be working hard to breathe. This, along with the increased metabolism producing fever, will increase oxygen demand even further. An appropriately sized continuous positive airway pressure (CPAP) or bag mask (BVM) can be used to reduce work of breathing or provide ventilations completely.^12,36,45

Circulation

Rapid and large-bore IV or IO access is important not only for initial fluid resuscitation, but also for possible blood product administration. As previously mentioned, recommended fluid administration is the standard 20cc/kg until any of the following occur:⁴³

• Signs/symptoms improve
• Rales
• Hepatomegaly
• MAP >65.

Fluid administration may continue up to 60cc/kg. This does not mean that no more fluid will be administered beyond 60cc/kg, but most offline EMS protocols stop at that point (septic shock). In some cases fluid administration in excess of 200cc/kg may be necessary.^12,36,45

Drugs/Differential
In some cases of severe sepsis or septic shock, pressor medications may be necessary to maintain the patient’s circulatory status. The following pressor agents are recommended for pediatric sepsis:^46,47

• Cold shock (compensating, cool extremities, delayed capillary refill): Epi 0.1–1 mcg/kg/min IV/IO infusion, titrate to effect
• Warm shock (decompensated, warm extremities, flash capillary refill): Norepi 0.1–2 mcg/kg/min IV/IO infusion, titrate to effect

While hyperglycemia is a common finding in pediatric septic patients, EMS providers should be alert for low blood sugar as well:⁴⁴

• Neonates <45 mg/dL: Administer glucose 0.5–1 g/kg IV/IO of D5%;
• Infants/children <60 mg/dL: Administer glucose 0.5–1 g/kg IV/IO of D10%.

Antipyretics such as Tylenol or Motrin may be considered according to local protocol to reduce fever both for patient comfort, as well as to reduce the physical demands the fever is placing on a body in shock.

When we consider that for every hour administration of antibiotics is delayed, patient mortality increases 7%, it seems only reasonable that antibiotics should be administered as early as possible, even outside of the hospital.48–50 Kevin T. Collopy, BA, FP-C, NRP, CMTE, clinical education coordinator for AirLink/VitaLink Critical Care Transport in North Carolina says, “Antibiotic treatment is important especially with patients who will undergo extended transport times. In these patients we can make a real difference in the amount of time it takes to get those antibiotics on board to begin fighting back the infection and its effects.”⁵¹

Not every EMS system can be equipped to provide adult or pediatric sepsis patients with antibiotics. Selection of proper antibiotics to administer before blood cultures can be obtained is only one challenge. The agreement of destination hospitals to continue this antibiotic therapy is another. EMS services seeking this level of service must be working in true “sepsis systems of care.”

EMS providers must also keep in mind other possible concurrent medical or trauma issues with sepsis patients. Especially when dealing with septic shock (refractory to fluids), remember to keep issues such as pneumothorax, pericardial tamponade and endocrine emergencies in your differential diagnosis.

What Is MAP?

Mean arterial pressure (MAP) is a measurement of cardiac output superior to blood pressure, yet is not frequently used by many EMS providers.

Normal MAP is between 70–110 mm/Hg and target MAP (treatment goal) is MAP >65 mm/ Hg. There are advanced ways to calculate map that involve different mathematical formulas depending on the patient’s heart rate, but a simple rule of thumb is [(2x Diastolic BP)+Systolic BP]/3.

Thus, if your patient had a BP of 100/70 it would be 70x2=140, plus the systolic of 100=240. 240 divided by 3 = 80 which is a perfectly normal MAP.

Of course, in many systems there is an even easier way of calculating MAP. On most monitors that take NIBP measurements, the MAP is displayed right next to the blood pressure.

Thermometry

When using a thermometer on a pediatric patient it is important to keep the following items in mind to obtain a clinically relevant and accurate temperature:

• Gold standards for kids is a rectal temperature
• Oral temperature is fine for older children and adults
• Axillary temps are not reliable
• Accuracy of tympanic thermometers is highly technique-dependent
• Accuracy of newer infrared temporal artery (TA) thermometry is also technique-dependent.

Conclusion

After nearly 50 surgical procedures and numerous complications Andrew McDonough passed away on July 14, 2007. The primary cause of death was sepsis triggered by a fungal infection.

Andrew’s story, along with the many others, can be found through the Sepsis Alliance (www.sepsisalliance.org), a charitable organization dedicated to raise awareness of sepsis among healthcare providers and the public.

Sepsis is a complex and deadly mixture of inflammatory, immune and coagulation responses resulting in a combination of distributive, hypovolemic and obstructive shock that often goes unrecognized by healthcare providers until it is too late. EMS providers can do plenty for pediatric victims of sepsis by simply following the ABCs.

For Andrew McDonough and the many children like him, EMS providers need to be heard and spread the word: Unrecognized sepsis kills kids.

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Rommie L. Duckworth, LP, is a dedicated emergency responder and award-winning educator with more than 25 years working in career and volunteer fire departments, hospital healthcare systems, and public and private emergency medical services. Currently a career fire captain and paramedic EMS coordinator, Rom is an emergency services advocate, a frequent speaker at conferences around the world, and a contributor to emergency services research, textbooks, and print and online media.