Post-Intensive Care Syndrome for the Pediatric Neurologist

Abstract

In recent years, the number of children who survive critical illness has steadily increased. However, lower mortality rates have resulted in a proportional increase in post-Intensive Care morbidity. Critical illness in childhood can affect a child’s development, cognition, and family functioning. The constellation of physical, emotional, cognitive, and psychosocial symptoms that begin in the Intensive Care Unit and continue after the patient and family return home has recently been termed Post-Intensive Care Syndrome (PICS). A conceptual model of the PICS experienced by children who survive critical illness, their siblings, and parents has been coined PICS-p. Due to their prolonged hospitalizations, the use of sedative medications, and the nature of their illness, children with primary neurologic injury are among those at highest risk for PICS-p.

The pediatric neurologist participates in the care of children with acute brain injury throughout their hospitalization, and remains involved after the patient leaves the hospital. For that reason, it is important for pediatric neurologists to become versed in the early recognition and management of PICS-p. In this review, we discuss the current knowledge regarding PICS-p and its risk factors. We also discuss our experience establishing Pediatric Neurocritical Care Recovery Programs at two large academic centers. Last, we provide a battery of validated tests to identify and manage the different aspects of PICS-p, which have been successfully implemented at our institutions. Dissemination of this ‘road map’ may assist others interested in establishing recovery programs, therefore mitigating the burden of post-Intensive Care morbidity in children.

A. Introduction

Recent estimates indicate that nearly 300,000 children are admitted annually to a Pediatric Intensive Care Unit (PICU) in the United States.^1,2 Over the past three decades, mortality in children admitted to the PICU has steadily decreased, with recent studies reporting an overall 2% mortality.³ However, children who survive a PICU admission often experience a complex array of physical, psychological and cognitive symptoms in addition to the morbidity associated with their primary ICU condition.⁴ This constellation of signs and symptoms has been recently named “Post-Intensive Care Syndrome –Pediatric (PICS-p, Figure 1)”.⁵ Although these symptoms may be subtle, they can have a profound effect on a patient’s health-related quality of life (HRQoL) and family functioning.^6–8

Figure 1.

Post-intensive Care Syndrome in pediatrics (PICS-p) framework. The patient and all members of the family are exposed to the patient’s illness and the PICU environment. Upon discharge, all members of the family contribute to the recovering child’s cognitive, emotional, physical and social health status, and each family member requires individual consideration. The child’s condition may improve, decline, or remain static over time.

From: Manning, JC et al. Pediatric Critical Care Medicine 2018; 19:298–300. Reprinted with permission.

Among critically ill children, those with primary neurologic disorders are at particularly high risk for PICS-p. Over 20% of PICU admissions are due to a primary neurologic illness or injury, and many others suffer secondary neurologic effects as part of their critical illness.⁹ The combination of primary and secondary brain injuries, lengthy hospitalizations, and exposure to invasive interventions¹⁰ puts children with these conditions at special risk for protracted and complicated recovery.¹¹ PICS-p symptoms including physical disability, neurocognitive deficits, psychosocial problems and impaired HRQoL are found in over half of children with acquired brain injury during the first year of their hospital recovery.^12–15 Families of children with neurologic disorders surviving critical care hospitalizations also endorse a high prevalence of psychological and social sequelae years after discharge.¹⁶

Pediatric neurologists are increasingly taking an active role in the care of critically ill children.¹⁷ Moreover, the pediatric neurologist has a unique role in providing care throughout a continuum that spans the PICU, inpatient ward, rehabilitation and outpatient follow-up. For this reason, it is important that pediatric neurologists become proficient in the early identification, management and prognostication of PICS-p. In this review, we discuss the current literature on PICS-p, with a focus on the role of the pediatric neurologist as a nexus between children with acquired brain injury, their experience in the PICU, and their re-integration back into their environment. We also review the experiences of separate multi-professional Pediatric Neurocritical Care Recovery services at two tertiary academic institutions which have a focus on early identification and management of PICS-p. Drawing from our early experience, we provide a battery of validated screening tools that have been successfully implemented by both our programs to assess the multiple dimensions of PICS-p, and the timing at which those tools are utilized (Supplementary Table 1). We also discuss our methodology used to assess Neuropsychological function in these patients (Supplementary Table 2). The information discussed here provides a ‘road map’ for other institutions interested in establishing Neurocritical Care Recovery programs.

B. Children are not small adults: factors to consider in the assessment of PICS-p

Impaired HRQoL is found in up to 80% of children after PICU discharge, across all ages.^18–20 Roughly one-quarter of children experience psychological sequela within 3 months after discharge from the PICU,²¹ with a residual 10–24% still experiencing psychological symptoms a year later.^22,23 Cognitive deficits in child survivors are particularly common in patients with traumatic brain injury or cardiac arrest.^24,25

Despite a robust body of literature on adult PICS^26–31, epidemiological data on PICS-p is sparse. Obtaining accurate assessments of the impact of critical illness in pediatrics is complicated by several factors. First among those are age and developmental stage at the time of critical illness. Young PICU survivors show higher rates of cognitive impairments, often in multiple domains, compared to older patients.³² Survivors of extracorporeal membrane oxygenation support in infancy tend to show more deficits over time, when both more detailed testing is possible and when developmental expectations are higher, exposing deficits that may not have been appreciated earlier.^33,34 Second, pre-morbid status is an important determinant of outcome. With modern therapies survival of children with severe chronic illnesses continues to rise. Those children are increasingly being admitted to the PICU late in their disease, and with a worse baseline (pre-morbid) status. A worse pre-morbid status translates into prolonged admissions, the need for more invasive procedures, and eventually worse outcomes.³⁵ A third factor that complicates accurate assessment of the impact of pediatric critical illness is the family’s function in relation to the child. A child survivor of critical illness is intimately connected to a larger family unit, and their own functionality and mental health is in many ways dependent upon the status of their parents’ and family’s health.^14,36,37 Parental Post traumatic stress disorder (PTSD) and mental health symptoms are reported in about half of parents in the year after the child’s discharge from the PICU, and their symptoms affect their child’s recovery.^38–40 Perhaps, further complicating this picture is the variability of acute stress symptoms in parents with regard to gender. Some data suggest that mothers of very young children are particularly susceptible, while fathers exhibit more stress as their child’s illness acuity increases.⁴¹

C. Risk factors for PICS-p

The risk factors for development of PICS-p are multi-factorial, and poorly understood. However, these risk factors can be categorized into three groups: (a) pre-morbid; (b) during critical illness; and (c) post-discharge (Table 1). Each of these categories represents an important phase disease process, with its own set of difficulties for the child and their families.

Table 1.

Risk factors for PICS-p can be divided into those affecting the child (shaded) and those affecting the family (unshaded).

Pre-morbid	During critical illness	Post-discharge
Age and developmental stage Pre-morbid conditions	Number of invasive procedures Severity of illness PICU length of stay Use of sedative medications Secondary complications of critical illness (i.e. mechanical ventilation, immune dysfunction, septic shock) Delirium Sleep disturbances	Limited Pediatric resources School re-insertion Somatic complaints (i.e. pain, sleep, muscle waste)
Maternal mental health Family functioning and coping skills Socioeconomic background	Social and economic support during PICU stay	Familiar post-traumatic stress disorder

C.1. Pre-morbid risk factors

Although the experience of critical illness is inextricably linked to changes in physical and mental health, there is also clear indication that pre-morbid health and well-being are important elements to one’s ability to manage those changes. Studies of adult survivors of critical illness repeatedly demonstrate that factors such as previous medical and mental health diagnoses, employment status, education level, and socio-economic status play important roles in the development, severity and persistence of PICS symptoms.^42–45 In children, pre-morbid mental health and well-being of their mothers exerts a strong influence on the child’s own adaptive behavior and emotional health,⁴⁶ and family functioning prior to the child’s critical illness can play a large role in the pace and completeness of PICS-p symptom resolution.⁴⁷ Post-discharge cognitive impairment may also be more common among children surviving ICU from lower socioeconomic backgrounds.³²

C.2. Risk factors during critical illness (ICU exposure)

Children who experience a greater number of invasive procedures, increased severity of illness, and longer duration of sedative medications have psychological symptoms of greater severity and duration compared to children who did not experience those complications.^4,48 Cognitive impairment may also be more common among children surviving ICU after needing mechanical ventilation, sedation, and pain management.³² For example, the largest RCT in critically ill children studying sedation practice (the RESTORE Trial) demonstrated a relationship between inadequate sedation, inadequate analgesia, longer duration of mechanical ventilation, and several other patient demographic factors and a decline in functional status at the time of hospital discharge, and impaired HRQoL six months later.⁴⁹ While certain baseline patient characteristics were found to be predictive of post discharge morbidity, so were the etiology of the respiratory failure, ventilation duration, and certain sedation regimens.⁴⁹ Another large study of pediatric sepsis survivors in a single, large U.S. PICU demonstrated that septic shock, immune dysfunction, and PICU length of stay were independently associated with failure to return to functional baseline (23.8% of the original study cohort of 790 children).⁵⁰ Although the long-term effects of delirium in children are largely unknown, there is increasing evidence that ICU delirium in children is associated with increased mortality, length of stay, hospital cost, and morbidity.⁵¹ Supporting this idea are the findings that the development of delusional memory in children during their PICU stay is associated with the later development of post-traumatic stress symptoms and PTSD.^10,52

Although less well studied than in adults, children also experience significant muscle wasting and ICU-acquired weakness, beginning within days of admission to the PICU.⁵³ Early mobilization alone and in combination with interventions targeting early extubation, sedative minimization, and healthy sleep can improve physical and functional outcomes in adult survivors.^54,55 How this relates to the pediatric experience has yet to be conclusively identified, though studies have shown early mobility to be well-tolerated and feasible in PICU populations.^56,57

Healthy sleep is vital for brain maturation and normal development, and is likely even more important after acute brain injury, given that sleep facilitates neuronal healing and reduces inflammation.^58,59 Circadian disruption, which can result from light, noise, medications, brain injury, and inflammation, is well documented in adult and pediatric ICUs.⁶⁰ Implications of disrupted circadian rhythms are vast and include impacts on multiple organ systems, immune dysfunction, and healing from injury.⁶⁰ Sleep disruption is also implicated in delirium, and sleep is often a target in delirium management.⁶¹ Environmental measures and pharmacologic interventions during ICU stays targeting healthy sleep are reported, but the impact of these measures on outcomes in children is unknown.

Lastly, the role of acute stress and other mental health symptoms experienced by parents during their child’s PICU admission in the development of their own PICS symptoms, and that of their children, has yet to be well studied. However, data suggest that social support⁶² and outlets for emotional expression³⁹ during their child’s ICU stay may help mitigate parental symptoms of PICS-p. Although small studies have suggested the benefit of patient and/or caregiver diary programs, a recent Cochrane Review was unable to conclusively confirm their benefit in reducing PICS symptoms.⁶³

C.3. Risk factors associated with the post-discharge environment

Families of ICU survivors consistently indicate a number of challenges with potential implications for their children’s outcomes, including limited pediatric resources in rural settings, perceived lack of awareness of PICS-p among many medical providers, and the substantial financial burden from medical costs, environmental adaptations, and missed work due to care responsibilities for their child.¹⁶ Parents express a desire for improved education surrounding PICS-p morbidities for families and their medical providers, improved communication between specialists and primary care providers after discharge, better access to educational materials, better access to mental health providers, and information about local support groups and accessing community resources.¹⁶

Outpatient providers are often tasked with managing a multitude of symptoms related to PICS-p. Among these, pain management and restoration of healthy sleep may have important implications for other PICS morbidities, including physical, cognitive, and psychosocial impairments.^15,64–66 Headaches and chronic pain are frequently reported among children surviving the ICU in the outpatient setting.¹⁵ Pain has implications for the psychological and cognitive well-being of children, impairing functional abilities, school performance, and social participation.⁶⁷ Sleep-wake disturbances including insomnia, somnolence, and sleep-related breathing disorders are reported in survivors of acute brain injury, but to date have been poorly quantified in children, particularly those requiring ICU care.^68,69 Our recent research highlighted the importance of sleep disturbance after PICU, showing 52% of patients have moderate to severe disturbances in several aspects of sleep.⁷⁰ There are several easily performed and validated sleep questionnaires available for use in infants and children (Supplementary Table 1).⁷¹

Consideration of the child’s entire family unit can also be of therapeutic benefit, as several studies have demonstrated a reduction in psychiatric morbidity in children and their parents when interventions primarily targeted to reduce PTSD symptoms in parents are deployed.⁷² There is also suggestion that early screening for parents at high risk for developing PTSD is feasible and may allow recovery teams to more efficiently use mental health resources.⁷³ However, how these families should be followed remains unclear. Although limited, there is suggestion that follow-up clinics may reduce parental anxiety and depression,⁷⁴ as well as offer providers a chance to intervene in a direct medical capacity.

D. A proposed model to address PICS-P in patients with acute brain injury

Over the past five years, our institutions, St. Louis Children’s Hospital (SLCH) and Doernbecher Children’s Hospital (DCH), have developed multi-professional Pediatric Neurocritical Care Recovery Programs to provide systematic evaluation and management of PICS-p.^15,120 SLCH is a 250 bed tertiary children’s hospital within the Washington University School of Medicine, located in St. Louis, Missouri. The SLCH PICU has approximately 2,200 admissions per year. DCH is a 145 bed tertiary children’s hospital within Oregon Health & Science University located in Portland, Oregon with approximately 1,300 admissions to the PICU annually. In both institutions, the multi-professional PICU Neurocritical Care team is composed of faculty in Pediatric Critical Care, Pediatric Neurology, and Pediatric Neuropsychology, with the additional service of social work and school liaison services at Washington University.

D.1. Inpatient PICS-p screening and prevention

Care for patients in our programs begins with acute ICU management. Neurologists are involved with management in primary neurologic diagnoses such as stroke, meningitis, status epilepticus, and traumatic brain injury, as well as secondary neurologic complications of critical illness such as seizures, headache, spasticity, and delirium. Patients with primary neurological diagnoses, and those with neurological complications of other primary illness receive inpatient consultation with a member of our programs providing PICS-p education and referral for follow-up. Depending on their level of alertness and ability to participate in assessments, patients receive inpatient neuropsychology consultations to collect historical information in an effort to avoid the ‘good old days’ bias (the tendency for parents/caregivers to underestimate premorbid problems and over attribute current problems to the neurological trauma),⁷⁵ and to provide coping strategies to families while in the ICU and initial accommodation recommendations for children pending outpatient assessment. In addition, some patients may also receive brief neuropsychological evaluations or serial neuropsychological screenings as part of their care with other service lines during their hospitalization (e.g., neurorehabilitation).

At present time, there is no accepted standard for the optimal timing of PICS-p screening. However, both our programs use simple standard tools available to assess for anxiety, depression, PTSD, and delirium in children and their parents (Supplementary Table 1).^76–78 Early screening has repeatedly demonstrated a correlation between early mental health and stress (in the ICU, or at the time of hospital discharge) and mental health outcomes 2–6 months later,⁷⁹ and can distinguish between those at low, medium or high risk for persistent symptoms at 12 months.^43,44,80 In addition, PICS-p education while in the PICU improves knowledge, understanding, and normalization of PICS-p for parents of PICU patients, and enables parents to identify better coping strategies.⁸¹ Similarly, brief structured anticipatory guidance provided to mothers at the time of hospital discharge has also been shown to improve the child’s behavior after return home, greater use of coping strategies by mothers, and less anxiety in the home environment after discharge compared to standard-care.^82,83 Early psychological intervention in the ICU can reduce mental health symptoms and use of psychiatric medication, even up to a year after discharge.⁸⁴ In addition to neuropsychological assessment, we utilize screening tools for strength, coordination, which can be quickly and easily performed in both inpatient and outpatient settings (Supplementary Table 1).^28,85

When available, early rehabilitation programs based in the PICU have proven to be safe, feasible, and of potential benefit, although there is insufficient data in pediatrics to confirm efficacy in reducing PICS-p symptom development at this time.⁵⁷ Perhaps most relevant to the pediatric neurologist, medical screening for PICU-related myopathy, neuropathic pain, and delirium, can all play a role in reducing the morbidity associated with acute brain injury and PICS-p.^86,87 When available, physiatrists, rehabilitation, and neuro-rehabilitation specialists can ease care transitions out of the ICU and inpatient wards for many patients and their parents, and provide a roadmap for the next phase of the child’s recovery. However, our research shows <10% of patients with primary neurocritical care diagnoses are discharged to inpatient rehabilitation facilities despite high rates of new functional disabilities at discharge.⁸⁸ The pediatric neurologist is paramount in the longitudinal care of these PICU patients with acquired brain injury not receiving rehabilitation services.

D.2. Post-hospital discharge PICS-p care

Perhaps the largest shift in the delivery of critical care over the past decade has been the shift from a uniformly inpatient focus to one that assumes the role and responsibilities of the ICU team continue past ICU and hospital discharge. Multi-professional ICU follow-up clinics for adults are increasingly described in the medical literature,^89,90 although whether these improve outcomes remains unclear.^91–93 However, some focused efforts have had better success, such as PICS education that continues past hospital discharge⁹⁴ and peer support programs.^95,96 Recent experience by the multi-professional PICU follow-up clinic at DCH reported that 87% of children required ongoing care beyond the initial outpatient visit.¹⁵ These were most commonly related to cognitive deficits (memory, attention) and psychological concerns (anxiety). Sleep disturbances were also reported in over 50% of patients, and 61% of patients required referral to other specialties for evaluation (physical and occupational therapy, audiology, ophthalmology, otolaryngology, counselling).¹⁵

Indications for a referral to the PICU follow-up clinic include traumatic brain injury, central nervous system infection, neuro-inflammatory diseases, and hemorrhagic or ischemic stroke. These patients are automatically referred by a member of the PICU staff following daily census review. Survivors of status epilepticus without another established neurologist and requiring critical care for >24 hours are also referred. Other patients (cardiac arrest, patients requiring extracorporeal membrane oxygenation, patients who experienced delirium) receive referrals at the discretion of attending providers. In our model, patients and families participate in an initial follow-up appointment between 4–6 weeks post-discharge for both programs. These appointments are integrated with a neurologist or intensivist. During the appointment, patients complete a relatively fixed neuropsychological screening battery administered by a neuropsychologist (Supplementary Table 2). This screening uses normed and standardized measures to assess premorbid functioning, executive functions (i.e., attention, processing speed, working memory, cognitive flexibility, self-monitoring), memory/learning, language, and bilateral fine motor dexterity. Aspects of this battery can be modified to meet patient needs, such as using measures that do not require a verbal response when patients are unable to speak. Gross motor coordination and visual processing are observed as part of the integrated medical exam. Neuropsychologists interpret this data in conjunction with neurologist assessments and clinical interviews to identify psychological, behavioral, and cognitive deficits, as well as to screen for family impact/stress and PICS-p. In interpreting the data from the appointment, care is taken to delineate what may represent a change in abilities as opposed to premorbid or longstanding concerns.

Findings from this initial appointment are summarized in a formal report that is used to help patients access needed services in the community and at school. Recommendations are also developed to address any PICS-p related challenges and can help address any premorbid concerns. In addition, both programs offer long term inter-professional follow-up as needed. This often includes neurologist follow-up for symptoms like headache, seizures, or weakness and a comprehensive neuropsychological assessment at 6–12 months post-discharge that utilizes a flexible test battery designed to meet the specific needs of each patient. The DCH program offers a monthly PICU survivor family support group and is in the additional process of developing a time-limited, family-based neuropsychology treatment clinic to treat the psychological aspects of PICS-p, intended to be holistic in its approach. Given the relative frequency that the appointment results in educational recommendations, at SLCH, families have access to a School Liaison to assist in ensuring that recommendations are appropriately carried out by the child’s school.

Preliminary results of our programs show that a substantial proportion of children have documented abnormalities in tone, strength, coordination, and significant disruption in sleep quality and mood.¹⁵ Over half of patients require ongoing care with physical therapy and less than one third were back in school at the time of initial follow-up. We also found that integration of neuropsychology into follow-up care resulted in recommendations being made for services or concerns not already addressed in 81% of cases, including mental health treatment and educational accommodations or special education services. Parents reported high satisfaction, endorsing the highest possible rating on 96% of all items, and reported that neuropsychological consultation improved their understanding and communication with their child, and helped them know what to expect during post-acute recovery.⁹⁷

The neurology portions of the appointments in our programs integrate assessments of all PICS-p sequelae to create multifaceted treatment recommendations. For instance, headaches may be treated with medication, but treatment is often paired with sleep management and psychotherapeutic intervention for comorbidities like anxiety and post-traumatic stress symptoms. Similarly, interventions for cognitive impairment often include management of physical sequelae, like sleep disturbance and pain, in addition to school accommodations harnessing cognitive strengths. Patients are also screened for mood disorders, HRQoL, and family functioning (Supplementary Table 1). Referrals are provided for social work and counselling as needed, and families are offered access to a monthly support group (DCH).

G. Conclusion

PICS-p is a multisystem complication of critical illness that requires intentional and systematic screening for diagnosis. PICS-p is optimally managed by an organized multidisciplinary team approach that includes longitudinal attention to recovery. Emerging literature suggests modifiable risk factors for PICS-p exist. Treatment includes consideration of the child’s age, developmental trajectory, and the role of parents and siblings as the child returns home to complete her/his recovery. Pediatric neurologists are an integral member of the care team, providing expertise in the evaluation, referral and management of PICS-p in both settings. The role of the pediatric neurologist extends beyond care for primary neurologic diagnoses, as secondary complications of many critical illnesses result in acquired brain injury and the sequelae of PICS-p.

Abbreviations

ICU

Intensive care unit

PICU

pediatric intensive care unit

PICS

post-intensive care syndrome

PICS-F

post-intensive care syndrome-family

PICS-p

post-intensive care syndrome-pediatric

PTSD

post-traumatic stress disorder

HRQoL

Health Related Quality of Life

SCCM

Society of Critical Care Medicine