Septic shock is a relatively rare but life-threatening condition in pediatric patients that can often be difficult to recognize in the emergency department. Once recognized, the emphasis of therapy is to reverse deficits in cellular respiration by increasing oxygen and other substrate delivery to tissue beds. Providing oxygen, improving tissue perfusion through augmentation of cardiac output, and administering antibiotics in a timely manner have all been shown to significantly improve outcomes in children with septic shock. Goal-directed therapy is relatively straightforward, emphasizes the need for effective surveillance and timely recognition of this disease process, and has the potential to significantly reduce morbidity and mortality. This review discusses how to identify specific populations at the greatest risk for septic shock, lays out the essential components of goal-directed therapy, examines potential pitfalls in management, and distinguishes additional ways that emergency clinicians can avoid the devastating consequences of septic shock in pediatric patients.
During a busy shift in the ED, an adolescent girl is wheeled back from triage. Her right arm is resting on the arm of the wheel chair, and she is holding her head. Her eyes are downcast, and she appears weak. She saw her doctor the day before with complaints of fever, nausea without vomiting, and generalized muscle aches. Her pediatrician diagnosed her with a flu-like illness and recommended plenty of fluids and ibuprofen as an antipyretic and analgesic. Earlier that morning when her parents went in to check on her, she was weak and could barely get out of bed. Her vital signs in the ED are temperature 39.4°C, heart rate of 141 beats/min, and blood pressure of 80/30 mm Hg. You begin examining the patient as a nurse inspects her upper extremities for a site to place a peripheral IV. She has a generalized erythematous nonpalpable rash, a slightly red posterior oropharynx, supple neck, clear lung fields, tachycardia with an otherwise normal cardiac examination, lower abdominal tenderness without peritoneal signs, and extremities noticeable for 1+ peripheral pulses, 2+ central pulses, and a capillary refill time of 4 to 5 seconds. You ask the respiratory therapist to provide her oxygen by facemask, and now that the nurse has established an IV line, you ask for a rapid bolus of fluid and start to consider antibiotics. The nurse asks, “What type of fluid and how fast?” You think to yourself, “Which antibiotic should I use, and what will I do if her condition continues to decline?” Then you recall that you didn’t ask when her last menstrual period occurred.
Just then, a nurse rushes back from triage with a 7-month-old boy who is minimally responsive, limp, mottled, and pale. The child’s breathing is not labored, and his airway seems patent. The nurse quickly hooks up the monitors and then starts working to obtain IV access. The child has a pulse, and the monitor shows a heart rate of 190 beats/min, which matches what you feel on examination. The blood pressure cuff inflates, deflates, and re-cycles without giving a reading. The pulse oximeter shows a poor waveform and also seems unable to yield a reading. After several minutes of failed attempts, the nurse looks up and says, “I don’t think I’m going to be able to get this IV in.” You reach for an intraosseous needle driver and needle, and you drill into the infant’s anterior tibia. You ask the nurse to check glucose on the aspirate from the intraosseous needle and start pushing normal saline into it. Realizing just how sick this infant is now, you ask the clerk to call the tertiary children’s hospital to arrange transfer. You obtain a basic history from the mother, and she tells you that her baby is usually healthy, but he has had a fever and a couple of episodes of vomiting overnight. While standing over this child, a number of thoughts come to mind at once: “This kid is obviously in shock. Vomiting can be seen with hypovolemic shock, but his history doesn’t suggest substantial volume loss. Why is this kid in shock? If not hypovolemic shock, what kind of shock is this? Should I go ahead and intubate this baby? Should I start antibiotics even if I don’t know what is causing the infection? When is that transport team from the children’s hospital going to call me back?”
A 3-year-old boy undergoing induction therapy for acute lymphoblastic leukemia presents to the ED, and initially, he looked pretty good. His mother brought him in because he had a fever of 39.1°C at home, and she had been instructed to bring him to the hospital for any fevers. He had been in reasonably good spirits when the nurse accessed his central line to obtain blood for laboratory work and cultures. Only a few minutes have passed when the nurse comes to you saying that she is worried about him because he is still febrile but is now tachycardic and sallow in appearance. You go back to his room and agree with the nurse’s assessment. You ask for 20 mL/kg of normal saline to be rapidly pushed as you confirm that antibiotics have been given. After 2 more 20-mL/kg boluses of normal saline, there is little improvement in his tachycardia or pulses, and his blood pressure is starting to decline. He has developed “flash” cap refill, and he is less interactive. You ask the nurses to prepare a dopamine infusion and start it at 10 mcg/kg/min. You ask yourself, “What else will help with his tachycardia and hypotension? I’ve given him fluids and antibiotics, and I’m starting inotropes. Are there other things that have been shown to help in this situation?
For an emergency clinician, there may be nothing more anxiety-provoking than caring for an infant or young child who presents in septic shock. Signs and symptoms concerning for septic shock include fever, tachycardia, evidence of decreased perfusion (such as poor pulses, mottled skin, or delayed capillary refill), decreased urine output, and altered mental status. Conditions that place a child at increased risk for shock include younger age, immunocompromised state, chronic medical conditions, or surgically placed hardware or devices.
Once a child’s condition has progressed to this point, it can be very difficult to determine the exact cause. Shock is a common pathway for a multitude of life-threatening illnesses and injuries, and septic shock is one of the most common forms of shock in developed countries. Fortunately, the fundamental principles of early goal-directed therapy for children in septic shock have been shown to reduce the mortality of this condition. These include: (1) providing oxygen, (2) aggressive fluid resuscitation, (3) early antibiotic administration, (4) inotropic support for fluid-resistant shock, and (5) stress-dose steroids for inotropic-resistant shock.
Now more than ever, septic shock is best approached as a “team sport” in which the emergency medicine physician coordinates the initial care with a team of practitioners in the emergency department (ED). Additionally, children whose shock state does not improve with initial interventions, there must be effective coordination with transport teams and colleagues in pediatric tertiary care centers’ intensive care unit (ICU) to ensure that, when indicated, further therapies are initiated and appropriate monitoring is performed while this transition of care proceeds.
Studies of septic shock in pediatric patients in the ED are somewhat limited. Most research on children with septic shock are usually studies of “pediatric shock,” which is a heterogeneous clinical entity of which septic shock is only one cause. Individual cases of pediatric shock are not common, and a single institution would have to study data spanning many years to have a reasonably sized study.
The cause of shock is often not immediately apparent on presentation to the ED or the ICU. Therefore, studies tend to be retrospective and rely on information that is only available as the case unfolds over time, which leads to studies that have limited applicability to ED care.
Children in shock are often critically ill, and some clinicians consider interventional or experimental studies to be unethical.1-3 Performing a study that substantially increases a child's risk for death is unappealing (to say the least) to many researchers, patients, and families.3 This leads to a paucity of relevant studies. Given the severity of illness, exceptions from informed consent may be needed to allow the performance of a study. Obtaining an exception from informed consent is an arduous process that few researchers have the resources or willingness to endure.3-5
It is impossible to compare treatments, for example, since many of the study populations assessing the treatment of shock in children include not just septic shock but also hemorrhagic shock from trauma, hypovolemic shock from a diarrheal illness, cardiogenic shock in children with congenital heart disease, and distributive shock from anaphylaxis. Any discussion of the literature on the treatment of septic shock in children must include the Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012.6 These guidelines were initially published in 2004, revised in 2008, and then revised again most recently in 2012. They contain the most updated evidencebased recommendations on the approach to managing septic shock and include specific considerations for treating children based on information available through early 2012, but it must be noted that these are consensus expert recommendations based on somewhat limited studies, which has lead to continued use of ineffective or even harmful therapies, simply because evidence is not available to refute their use.7,8 Some reasons cited for using these ineffective therapies include: a “love of the pathophysiological model (that is wrong),” “a need to do something,” and “clinical experience.”8
Another problem arises when the results of studies involving adults only are applied to the care of children. An example that illustrates this point nicely are the studies demonstrating that activated protein C is an effective therapy for adults in septic shock.9-11 However, a multicenter study of activated protein C for the treatment of children in septic shock was suspended due to excessive complications and a lack of demonstrated benefit over placebo.12 In this case, there was an increase in intracranial bleeding, particularly in children aged < 2 months. Reliance on adult data to guide the care of children in this instance would have been harmful.
Finally, some of the most fundamental concepts in the management of shock are supported by very small studies. For example, critically ill children are often found to be hypoglycemic on presentation. Studies that directly address this, however, are rare. One of the best known studies is by Losek, who reported on 49 children undergoing resuscitation, 9 of whom were discovered to be hypoglycemic.13 Another example involves fluid resuscitation. Although nearly universally recommended, few studies have directly explored whether or not fluid resuscitation is beneficial in management of shock. An early and widely cited study by Carcillo et al addresses fluid resuscitation, but it only included 34 children.14 Systematic reviews regarding fluid resuscitation seldom evaluate the unproven “facts” and instead compare 2 similar therapies.15,16
1. “He wasn’t hypotensive, so I didn't think he was in shock.”
In children, sometimes the only signs of compensated shock may be tachycardia and irritability, which are common findings. Although formal definitions of shock stress the presence of hypotension, it is important to note that it is not required to be present in children for the diagnosis of septic shock to be made.
2. “The pulse oximetry reading was normal, so I didn't give oxygen.”
The primary deficiency in shock is insufficient substrate for cellular respiration. The most essential substrate is oxygen. In all cases of presumed shock, supplemental oxygen should be provided at the onset of therapy.
3. “I waited to give a second bolus because I didn’t want to fluid overload this child.”
Children with symptoms of shock can have fluid deficits that are far greater than may initially be estimated. An initial fluid bolus of 20 mL/kg of isotonic crystalloid over 5 to 10 minutes is only the start of resuscitation. Continuous reassessment is essential. Except for children in cardiogenic shock, those with underlying congenital cardiac disorders, and possibly those with diabetic ketoacidosis, most children in shock benefit from the administration of relatively large fluid volumes.
4. “I gave the girl 60 mL/kg of normal saline, but it didn't seem to help. How could that not be enough?”
Especially in cases of ongoing fluid losses due to vomiting and diarrhea, both the fluid deficit and the ongoing losses need to be replaced.
5. “I don’t understand how she decompensated in the CT scanner. She looked fine 2 hours ago.”
Resuscitation of a child in shock requires that a therapy is not only implemented, but also that the results of that therapy are evaluated. Ongoing reevaluation of the child allows for additional appropriate therapy, as children who have been in shock can quickly decompensate.
6. “I didn’t give antibiotics for this child who was in shock because I couldn’t find a source of infection.”
Although it can be difficult to make a definitive diagnosis of shock caused by a bacterial infection, if other causes cannot be excluded with some confidence, timely administration of antibiotics may be lifesaving.
7. “The chest x-ray was normal, and there weren’t any infiltrates or effusions indicating a problem with the boy's heart. But I guess now that I take another look, the heart does seem big.”
Although dilated cardiomyopathy is not a common cause of shock, an enlarged heart can be seen on chest radiographs. Therefore, it should be considered in the differential, as the treatment for dilated cardiomyopathy is different from treatment for other causes of shock.
8. “I’ve never given dopamine to a child, so I just kept giving fluids.”
If, after the administration of 60 to 100 mL/kg of fluid, there is insufficient improvement in tissue perfusion, inotropic support should be initiated. Ideally, this is provided through a central venous line, but in some situations, it must be provided through whatever venous access is available, including a peripheral venous line or an intraosseous line.
9. “I thought fluids would be enough to treat the shock. Why should I have given hydrocortisone to this child?”
Children who are on chronic steroids or who are steroid-dependent have increased steroid needs during even minor acute illnesses. Appropriate doses of steroids can successfully reverse shock.
10. “The little girl didn't have a fever, so I was not concerned about septic shock.”
Although fever often accompanies infection, it is not required in order to make the diagnosis of SIRS, sepsis, or septic shock. The use of nonsteroidal anti-inflammatory drugs, the use of immunosuppressive agents, or innate patient features can alter the expected febrile response to infection.
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.
To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study will be included in bold type following the references cited in this paper, as determined by the author, will be noted by an asterisk (*) next to the number of the reference.
Adam M. Silverman, MD;
April 2, 2015