Shock in children in resource-limited settings: Recognition

INTRODUCTION — The recognition of shock in children treated in resource-limited settings is provided here. The management of shock in children treated in resource-limited settings, the recognition and treatment of septic shock in settings with abundant resources, and the treatment of neonatal sepsis and shock are discussed separately:

●(See "Shock in children in resource-limited settings: Initial management".)

●(See "Septic shock in children in resource-abundant settings: Rapid recognition and initial resuscitation (first hour)" and "Septic shock in children in resource-abundant settings: Ongoing management after resuscitation".)

●(See "Neonatal shock: Etiology, clinical manifestations, and evaluation" and "Neonatal shock: Management".)

TERMINOLOGY

Shock versus circulatory impairment — Shock is a life-threatening condition that occurs when the circulatory system fails to provide adequate oxygenation and perfusion to the body and, as a result, vital organs become hypoxic [1]. For resource-limited settings, The World Health Organization Emergency Triage, Assessment and Treatment Guidelines (WHO ETAT) have established a common definition for circulatory impairment and shock for low- and middle-income countries (LMICs) that uses the following physical findings [1]:

●Cold extremities

●Prolonged capillary refill >3 seconds

●Weak/ fast pulse

One or two of these findings is consistent with circulatory impairment; all three findings are needed to diagnose shock. This phased definition acknowledges that the physiology of shock exists on a spectrum and is similar in principle to the definitions of compensated versus hypotensive shock used by the Pediatric Advanced Life Support Course [2]. (See 'Stages and classification of shock' below.)

This definition of circulatory impairment and/or shock in children is most relevant to practice in resource-limited settings without ready access to blood pressure measurements because it can be used by clinicians in austere environments. However, the WHO criteria for circulatory impairment and shock do not account for the underlying cause nor physiology that may be predominant. Therefore, it is critical for clinicians to use additional history, physical examination findings, and available laboratory and ancillary diagnostic tools to identify and begin proper treatment for the specific type and cause of shock. (See "Initial evaluation of shock in children".)

For example, children who have a suspected infection (eg, febrile) with circulatory impairment are similar to children with severe sepsis with compensated shock in resource-abundant settings [1,3,4]. Children with suspected infection and shock by the World Health Organization (WHO) definition according to clinical findings (table 1) or systolic blood pressure (table 2) are similar to children with hypotensive septic shock in resource-abundant settings. These distinctions are important because fluid therapy in resource-limited settings is determined by whether the child has severe sepsis or septic shock. (See "Shock in children in resource-limited settings: Initial management", section on 'Fluid therapy'.)

A key difficulty in the assessment of shock in children in resource-limited settings has been the variation in diagnostic criteria. The WHO definition of shock provides one approach for resource-limited settings; however, variations in diagnostic criteria persist, which inhibit standardization in both clinical settings and in the research that informs management recommendations.

Resource-limited settings — For the purposes of this topic, resource-limited settings describe regions where access to advanced pediatric critical care and trained critical care personnel is variable or not available, and the therapies essential to successful treatment of shock cannot be reliably performed, including:

●Advanced airway management and respiratory support (eg, high-flow nasal cannula oxygen therapy, bilevel positive airway pressure (BiPAP), and mechanical ventilation)

●Central venous and arterial blood pressure monitoring

●Continuous infusions of inotropic medications

Throughout the world, the majority of children with shock are cared for in resource-limited settings [5]. Significant regional variation exists across the globe related to available resources for diagnosis, treatment, and monitoring of critically ill children. Even within individual low- and middle-income countries (LMIC), significant variations in the ability to provide critical care, inside or outside of a formal intensive care unit, may exist from facility to facility.

Perhaps most importantly, the term "resource-limited setting" also refers to clinical environments that lack adequate human resources, either in the number of providers available or the training of those who are tasked with caring for children. For example, a nurse-to-patient ratio in a hospital in sub-Saharan Africa may be much lower than in Europe, the United Kingdom, or the United States. Moreover, in resource-limited settings referral systems, retrieval systems and pre-hospital care are often either non-existent or significantly limited. This situation together with the financial and safety limitations on travel faced by families all result in delayed presentation for care and more advanced critical illness upon presentation [6-10].

Initial research and recommendations for the diagnosis and treatment of shock in children were developed almost exclusively with data from pediatric facilities in high-resourced, high-income countries (HIC) where access to pediatric critical care and adequate numbers of trained and experienced clinical staff are widely available [11]. Furthermore, initial recommendations for the recognition and management of shock were developed based primarily upon data derived from populations where rates of acute and chronic malnutrition, anemia, malaria and other infectious diseases are low and where vaccination rates are high [12,13]. Subsequent evidence has found that children with shock in resource-limited settings require a different approach to prevent excess mortality, especially pertaining to fluid resuscitation. (See "Shock in children in resource-limited settings: Initial management", section on 'Fluid resuscitation'.)

Low- and low middle-income countries (LICs and LMICs) — The World Bank classifies countries for the purposes of economic and financial development services based upon national income per person or gross national income per capita as [14]:

●Low-income

●Low-middle income

●High-middle income

●High-income

From the standpoint of health care capability, resource-limited settings with no available intensive care are most common in low-income countries (LICs) and low-middle income countries (LMICs). Resource-limited health care may also exist in certain parts of high-middle income countries (HMICs) and high-income countries (HICs) because of maldistribution of health care capability relative to population. Nevertheless, access to resource-abundant health care settings still remains much greater for individuals living in HMICs or HICs compared with LICs or LMICs.

STAGES AND CLASSIFICATION OF SHOCK — The stage of shock identifies the severity of shock while the classification of shock provides the underlying cause and necessary interventions needed to reverse shock:

●Stages of shock – The stages of shock in children exist along a continuum and are identified by clinical findings (see "Pathophysiology and classification of shock in children", section on 'Stages of shock'):

•Compensated shock – Children with compensated shock have:

-Normal systolic blood pressure

-Tachycardia

-Decreased tissue perfusion (initially, prolonged capillary refill advancing to decreased pulses, cool skin, and decreased urine output as shock progresses)

•Hypotensive shock – Children with hypotensive shock have:

-Decreased systolic blood pressure

-Worsening tachycardia and tissue perfusion

-Evidence of inadequate end-organ perfusion (eg, oliguria and altered mental status)

•Irreversible shock – Without timely recognition and treatment, irreversible shock occurs and is marked by coma, acute kidney injury, liver failure, cardiovascular collapse, and death.

In resource-limited settings, when blood pressure measurement is not feasible, the WHO defines clinical features of shock and circulatory impairment (table 1). Patients who meet the WHO definition of shock are managed similarly to patients with hypotensive shock in resource-abundant settings; children with circulatory impairment often meet the definition of compensated shock used in resource-abundant settings but are managed with lower volumes and slower rates of fluid repletion based on evidence of harm in resource-limited settings. (See "Shock in children in resource-limited settings: Initial management", section on 'Volume and rate' and "Shock in children in resource-limited settings: Initial management", section on 'Risk of harm'.)

●Classification of shock – Shock is classified into four types based upon pathophysiology (algorithm 1) (see "Pathophysiology and classification of shock in children"):

•Hypovolemic shock (eg, hemorrhagic, gastrointestinal losses)

•Cardiogenic (eg, myocardial dysfunction, arrhythmia)

•Obstructive (eg, pneumothorax, pericardial effusion, pulmonary embolus)

•Distributive (eg, septic shock, neurogenic shock, anaphylactic shock, toxic shock, endocrine shock)

It is helpful for clinicians to understand the basic pathophysiology that leads to hypoperfusion of tissues and the relevant physiologic processes (table 3). In addition, correct classification of shock is important to guide interventions that will reverse shock. (See "Shock in children in resource-limited settings: Initial management", section on 'Approach to initial stabilization'.)

However, children frequently present with a "mixed shock" physiology with multiple pathways that combine to impair tissue perfusion [15]. In resource-limited settings, unique comorbidities such as severe anemia and/or malnutrition also complicate classification of shock and its management. (See "Shock in children in resource-limited settings: Initial management".)

EPIDEMIOLOGY — Hypovolemic shock from infectious diarrhea with dehydration and septic shock account for the majority of pediatric shock cases worldwide and significantly contribute to the global burden of childhood disease [16-19]. In 2017, over 20 million cases of sepsis were estimated to occur in children <5 years old with another 5 million estimated cases happening in children 5 to 19 years old [5]. Among children <5 years, diarrheal illness, neonatal disorders, and lower respiratory diseases were the most common causes of death. While global case-fatality rates for severe sepsis and septic shock have improved over the years, disparities between high-income countries (HIC) and low- or low middle-income countries (LICs and LMICs) persist for both the prevalence of septic shock and the case fatality rate [5]. Similarly, traumatic injury with hemorrhagic shock accounts for over 900,000 fatalities per year in children ≤18 years old, but 95 percent of these deaths occur in LICs/LMICs [20].

The poorer outcomes for shock in LICs and LMICs can be attributed to several factors that contribute to greater complexity and degree of illness for children presenting with septic shock in resource-limited settings and that pose major challenges to timely recognition and treatment:

●High prevalence of comorbid conditions – Important comorbid conditions that contribute to an increased prevalence of shock, increased severity of shock, and increased treatment complexity in children living in resource-limited settings include [21]:

•Malaria

•Dengue

•Malnutrition

•HIV

•Diarrheal illness (eg, cholera)

•Chronic anemia

In resource-limited settings, the clinician must look for and treat these conditions in addition to managing shock. Malaria, dengue, and diarrheal illness may also be primary causes of shock.

●Patient access to timely and quality care – Access to high quality care varies across the globe and within individual countries. However particular challenges with access exist for those living in rural settings within low- and low middle-income countries (LICs/LMICs). In these settings, the "three delays" model, first developed to explain maternal deaths, identifies significant factors that contribute to childhood mortality [10,22]:

•Delay in seeking care – Patients often seek non-allopathic/traditional treatment close to home prior to presentation to a health center or hospital [23,24]. This behavior delays definitive treatment. Furthermore, the traditional medication is usually unknown and can cause major adverse effects.

On the other hand, engagement with the traditional medicine community may also present some opportunities if the local traditional medicine provider is willing to help encourage caregivers of ill children to bring them to a health care facility [25].

•Delay in time to definitive care – After caregivers decide to seek standard medical care, most children in LIC/LMICs have a long transport time to health care facilities. For example, a geocoded inventory of public hospitals across 48 countries in sub-Saharan Africa found that 29 percent of people live more than two-hours travel time from the nearest hospital [8].

•Delay in treatment – Once at the health care facility, timely treatment is sometimes hampered by lack of equipment, medications, trained and experienced health care staff, and established procedures, and also challenged by the high volume of patients seeking care. For example, in a cross-sectional survey of central and district hospitals in Malawi, readiness for emergency and critical care was most commonly hampered by physical space, lack of equipment, and clinical protocols; district hospitals in general had low readiness compared with central hospitals [6]. As a result, health providers in LMICs often give less than half of recommended evidence-based care [26].

●Resources for diagnosis and etiology of shock – Ancillary studies used in resource-rich health care facilities for the recognition, characterization, and management of shock are frequently absent in resource-limited settings. In LIC/LMICs clinicians must rely more heavily on the history, physical examination and understanding of local epidemiology [6,27,28]. A cross-sectional survey distributed internationally to health care providers working in resource-limited settings found significant disparities in the availability of essential resources for the care of critically ill children in LMICs as compared with HICs, including [29]:

•ICU availability

•Advanced airway equipment and mechanical ventilation

•Staffing

•Renal supportive therapy

•Invasive monitoring

In a separate survey of 73 centers in 34 countries (34 from high-income countries and 39 from LMICs), pediatric intensive care units in LMICs had a similar overall disease burden but fewer critical care specialists, less access to hemodialysis, and fewer elective postoperative patients who are more likely to be stable [30].

Other important resource constraints that are common throughout LMICs and critical in the management of shock in children include limitations on the availability of blood transfusion [31,32] and adequate stocks of antibiotics recommended per national guidelines [33].

RAPID RECOGNITION — During the initial assessment of children without a history of trauma, clinicians must promptly determine if a child is in a physiologic state of shock and identify the etiology and most likely type of shock present (algorithm 1). Most clinicians working in resource-limited settings must rely on history, physical examination, and very limited diagnostic testing. (See "Initial evaluation of shock in children".)

As described below, red flag findings and danger signs are used to quickly identify children with the greatest severity of illness. In addition, malnutrition and malaria/severe anemia are common and important comorbidities in resource-limited settings that impact triage, recognition, and treatment of shock in children. (See 'Comorbid conditions' below.)

The rapid assessment of the pediatric trauma patient with shock follows the same principles as advanced trauma life support, as provided separately. (See "Trauma management: Approach to the unstable child".)

Red flag findings of circulatory impairment and shock — The World Health Organization Emergency Triage and Treatment (WHO ETAT) guidelines and definitions provide the commonly used definition for circulatory impairment and shock throughout resource-limited settings in low- and low middle-income countries by using the following physical examination findings [1]:

●Cold extremities

●Prolonged capillary refill >3 seconds

●Weak/fast pulse

One or two of these findings is consistent with circulatory impairment; all three findings are required to diagnose shock. This phased definition acknowledges that the physiology of shock exists on a spectrum and is similar in principle to the constructs of compensated versus hypotensive shock used throughout high middle and high income countries [2]. (See 'Stages and classification of shock' above.)

This definition of circulatory impairment and/or shock in children is most relevant to practice in resource-limited settings because it can be used by clinicians working in austere environments and without ready access to blood pressure measurement. However, it is important to recognize that the WHO definition of shock and circulatory impairment does not account for the underlying cause nor physiology that may be predominant. (See 'Clinical classification of shock' below.)

The WHO also provides age-based thresholds for hypotension (table 2) when blood pressure measurement is feasible. Most health facilities in low- and middle-income countries use the WHO thresholds for hypotension. In addition, Pediatric Advanced Life Support guidance provides the 5^th percentile for systolic blood pressure as an alternative target, which is also the one primarily used in resource-abundant settings and estimated as follows:

●Term neonates (0 to 28 days): >60 mmHg

●Infants (1 to 12 months): >70 mmHg

●Children (1 to 10 years): >70 mmHg + (child's age in years x 2)

●Children >10 years: >90 mmHg

Therefore, it is critical for clinicians to use additional history, physical examination findings, understanding of local epidemiology, and available laboratory and ancillary diagnostic tools to identify the type of shock and to begin appropriate treatment. (See "Sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis" and "Septic shock in children in resource-abundant settings: Rapid recognition and initial resuscitation (first hour)".)

Danger signs of imminent decompensation — Initial evaluation should also include an assessment for other danger signs of imminent decompensation, as outlined in the WHO ETAT guidelines with priority given to children with [1]:

●Obstructed breathing

●Central cyanosis

●Severe respiratory distress

●Convulsions

●Diarrhea plus any two of the following:

•Lethargy

•Sunken eyes

•Decreased skin turgor

●Coma or Altered Mental Status categorized as follows (AVPU):

•A – Alert

•V – Responds to Voice

•P – Responds to Pain

•U – Unresponsive

Alternatively, in malaria endemic regions, the Blantyre Coma Scale (BCS) has been validated as a tool to assess mental status in children (table 4) (see "Treatment of severe malaria", section on 'Clinical evaluation').

Any of the following features indicate high risk of decompensation and need to prioritize the child for rapid treatment:

●Any ETAT danger signs

●A mental status of V, P, or U

●BCS ≤ 3

STABLIZATION — Children with red flag findings or danger signs indicating shock require rapid triage and management prior to comprehensive evaluation, as discussed separately. (See "Shock in children in resource-limited settings: Initial management", section on 'Approach to initial stabilization'.)

EVALUATION — After stabilization, all children with shock require a comprehensive history and physical examination that is supplemented, whenever available, by ancillary studies.

History — The historical elements of greatest importance for children in shock are provided separately. (See "Initial evaluation of shock in children", section on 'History'.)

Historical findings commonly found in children with shock in resource-limited settings and important for management decisions include:

●Fever or hypothermia suggesting infection

●Vomiting and diarrhea from gastroenteritis

●Trauma with significant injury and/or ongoing bleeding

●Medications for treatment of malaria, tuberculosis (TB), or HIV and herbal or healer-administered medications

●Past medical history, especially:

•TB or HIV infection or exposure

•Sickle cell disease or thalassemia

Physical examination — After assessing for red flag findings and danger signs, patients should undergo a complete physical examination to further classify the type of shock and identify comorbidities:

●Vital signs – Children with shock usually are tachypneic and tachycardia. The WHO provides age-based thresholds for hypotension (table 2) [1]. Otherwise, diagnose hypotensive shock based upon red flag findings indicating circulatory impairment (table 1).

●Degree of dehydration – Look for degree of dehydration using the WHO criteria (table 5).

●Signs of sepsis – Identify sources of infections and clinical findings of sepsis, as described in detail separately. (See "Sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)

●Nutrition status – Degree of wasting determined by weight for height per the WHO standards and mid-upper arm circumference along with edema classify the degree of malnutrition (table 6). (See 'Comorbid conditions' below.)

●Malaria – In endemic regions, signs of malaria include high fever (acute or episodic), jaundice, and splenomegaly. Patients with severe malaria may have lethargy, coma, convulsions, mucosal bleeding, and petechiae (table 7). (See 'Comorbid conditions' below.)

●Severe anemia (causes other than malaria) – With the exception of a sickle cell sequestration crisis, pallor from other causes of anemia often do not have accompanying splenomegaly. (See 'Comorbid conditions' below.)

Comorbid conditions — Common comorbid conditions among children in resource-limited settings include malnutrition, severe anemia, and malaria:

●Malnutrition – Severe acute malnutrition (table 6) is associated with one of two classical syndromes, marasmus (wasting without edema) or kwashiorkor (edematous malnutrition) (table 8). Clinical features of marasmus, kwashiorkor, or a combination of the two (marasmic kwashiorkor) are important to recognize because they complicate fluid management and are accompanied by hypoglycemia, hypothermia, and immune suppression. (See "Malnutrition in children in resource-limited settings: Clinical assessment".)

●Malaria – In endemic regions, children may present with severe malaria with multiple organ manifestations including shock (table 7). Severe anemia in these patients is defined as a hemoglobin concentration ≤5 g/dL or plasma cell volume [PCV]/hematocrit [HCT] ≤15 percent in children <12 years of age according to the WHO guidance for high transmission regions. However, some experts use <6 g/dL (PCV/HCT 18 percent). These patients require antimalarial medication as well as an individualized approach to blood transfusion and fluid administration, as described separately. (See "Treatment of severe malaria".)

●Anemia – Children with shock may also have severe anemia caused by either chronic iron or other nutrient deficiency or because of an acute condition such as severe malaria or sickle cell crisis. In these patients, specific indications for blood transfusion in resource-limited settings may take priority over fluid resuscitation. (See "Shock in children in resource-limited settings: Initial management", section on 'Nonhemorrhagic shock and severe anemia (blood transfusion)'.)

Ancillary studies — For children in shock in resource-limited settings, laboratory studies are obtained when intravenous access is obtained for fluid resuscitation and typically include:

●Rapid blood glucose

●Malaria Rapid Diagnostic Testing and/or thick and thin blood smear

●Hemoglobin and/or hematocrit

●Lactate

●Blood culture

●Rapid HIV testing in high prevalence areas

●Urine dipstick/microscopy and culture

Recommendations for laboratory assessment of shock in resource-abundant settings are provided separately. (See "Initial evaluation of shock in children", section on 'Ancillary studies'.)

In resource-limited settings, plain radiographs and point of care ultrasound (POCUS) are the imaging modalities that are most frequently available:

●Plain radiographs – An anterior-posterior and lateral chest radiograph is indicated for children with shock who present with tachypnea, rales, wheezing, hypoxemia, or who do not respond to initial treatment. Key findings include:

•Bronchopneumonia

•Pulmonary edema with increased heart size suggesting fluid overload, cardiomyopathy (myocarditis), or congenital heart disease

•Small heart size suggesting hypovolemia

●Point of care ultrasonography (POCUS) — When available and performed by trained and experienced clinicians, POCUS has emerged as a clinical tool in high-income countries for the evaluation and management of children presenting in shock and shows promise for resource-limited settings [34-38]. For shock in particular, POCUS can provide rapid detection of cardiac tamponade [39] or pneumothorax while also giving a global overview of cardiac function and fluid status [40].

CLINICAL CLASSIFICATION OF SHOCK — The clinical classification of shock guides further management. An approach to the classification of shock based upon patient evaluation is provided in the algorithm (algorithm 1) and discussed in detail separately. (See "Initial evaluation of shock in children", section on 'Clinical classification of shock'.)

A combination of clinical findings helps differentiate hypovolemic from septic shock (table 9), which are the two most common types of shock seen in resource-limited settings. However, mixed forms of shock are common in resource-limited settings and unique comorbidities, such as severe anemia and/or malnutrition, also complicate classification of shock and its management, especially the approach to fluid resuscitation. (See 'Comorbid conditions' above and "Shock in children in resource-limited settings: Initial management", section on 'Approach to initial stabilization'.)

GUIDELINES — While WHO guidelines provide a framework for practice in resource-limited settings, they may not adequately address variability in regional or local epidemiology of shock, resources, and capability [41-43]. Furthermore, WHO guidelines frequently take a significant amount of time to incorporate the latest evidence. More specific national, regional, and local guidelines for the diagnosis and treatment of pediatric shock may be available. Clinicians must be familiar with these guidelines wherever they may be practicing.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sepsis in children and adults" and "Society guideline links: Shock in children".)

SUMMARY AND RECOMMENDATIONS

●Topic scope – This topic describes the recognition of children with shock in resource-limited settings (RLS), primarily located in low- and low-middle income countries where the availability of advanced pediatric intensive care is variable or not available, and the advanced therapies such as endotracheal intubation with mechanical ventilation, central venous and arterial access, and continuous vasoactive infusions cannot be reliably performed. (See 'Resource-limited settings' above and 'Low- and low middle-income countries (LICs and LMICs)' above.)

●Epidemiology – Hypovolemic shock from infectious diarrhea with dehydration, hemorrhagic trauma, and septic shock account for the majority of pediatric shock cases worldwide and significantly contribute to the global burden of childhood disease in RLS. (See 'Epidemiology' above.)

●Rapid recognition – During the initial assessment of children without a history of trauma, clinicians must promptly determine if a child is in a physiologic state of shock and identify the etiology and most likely type of shock present (algorithm 1). Most clinicians working in resource-limited settings must rely on history, physical examination, and very limited diagnostic testing.

The World Health Organization Emergency Triage, Assessment and Treatment Guidelines (WHO ETAT) provide clinical definitions for shock and impaired circulation for use in RLS (table 1). The WHO also provides age-based thresholds for hypotension in these children that are commonly used to determine fluid therapy (table 2). (See 'Red flag findings of circulatory impairment and shock' above.)

Initial evaluation should also include an assessment for other danger signs of imminent decompensation. (See 'Danger signs of imminent decompensation' above.)

The rapid assessment of the pediatric trauma patient with shock follows the same principles as advanced trauma life support as provided separately. (See "Trauma management: Approach to the unstable child".)

●Stabilization – Children with red flag findings or danger signs indicating shock require rapid triage and management prior to comprehensive evaluation, as discussed separately. (See "Shock in children in resource-limited settings: Initial management", section on 'Approach to initial stabilization'.)

●Evaluation and classification of shock – The clinical classification of shock guides further management and the expected clinical course. The evaluation of children in RLS with shock follows the same approach as for other settings (algorithm 1). A combination of clinical findings helps differentiate hypovolemic from septic shock (table 9), the most common types of shock in RLS. (See "Initial evaluation of shock in children", section on 'Evaluation'.)

Evaluation must also identify history of HIV infection, degree of malnutrition (table 6), severe anemia, and, in endemic regions, severe malaria (table 7). These comorbidities increase the likelihood of a mixed shock presentation and frequently alter the approach to fluid resuscitation. (See 'Comorbid conditions' above and "Shock in children in resource-limited settings: Initial management", section on 'Fluid resuscitation'.)