a b s t r a c t

Background: A significant proportion of children with SARs-CoV-2-related illnesses have been admitted to the pediatric intensive care unit (ICU), although often for closer monitoring or concerns related to comorbidities or young age. This may have resulted in inappropriate ICU admissions, waste of resources, ICU overcrowding, and stress for young patients and caregivers.

The Pediatric Intermediate Care Unit (IMCU) may represent an appropriate setting for the care of children whose monitoring and treatment needs are beyond the resources of a general pediatric ward, but who do not qualify for critical care.

However, research on pediatric IMCUs and data on their performance is very limited. Methods: We conducted a single-center retrospective study including all patients aged 0-18 with acute COVID-19 or Multisystem inflammatory syndrome in children , admitted to a newly established stand-alone 12-bed pediatric IMCU at Gaslini Hospital, Genoa, Italy, between 1 March 2020 and 31 January 2022.

Each IMCU room has a multiparameter monitor connected to a control station and can be equipped as an ICU room in case of need for escalation of care, up to ECMO support. IMCU and ICU are adjacent and located on the same floor, allowing a timely escalation from intermediate to critical care in the IMCU, with staff changes without the need for patient transfer.

Results: Among 550 patients hospitalized for acute COVID-19 or MIS-C, 106 (19.2%, 80 with acute COVID-19, and 26 MIS-C) were admitted to IMCU. Three of them (2.8%) required escalation to critical care due to the worsening of their conditions. Forty-seven patients (44%) were discharged home from the IMCU, while the remaining 57 (55%) were transferred to low-intensity care units after clinical improvement.

Conclusions: In our study, the need for pediatric ICU admission was low for both acute COVID-19 patients (0.8%) and MIS-C patients (3.1%) compared to the literature data. The IMCU represented an adequate setting for children with Covid-19-related illness who need a higher level of care, but lack strict indications for ICU admission, thus preventing ICU overcrowding and wasting of economic and logistical resources. Further studies are needed to better assess the impact of an IMCU on hospital costs, ICU activity, and long-term psychological sequelae on children and their families.

(C) 2022

1. Introduction

Abbreviations: ICU, intensive care unit; MIS-C, multisystem inflammatory syndrome in children; IMCU, intermediate care unit; ED, Emergency Department; ECMO, extracorporeal mechanical oxygenation; ARDS, acute respiratory distress syndrome.

* Corresponding author at: Terapia Semintensiva, IRCCS Istituto Giannina Gaslini, via Gerolamo Gaslini 5, 16147 Genoa, Italy.

E-mail address: [email protected] (G. Brisca).

Although SARS-CoV-2 infection was initially considered a mild disease in children, recent studies have shown up to 30% incidence of severe COVID-19, defined as the need for pediatric intensive care (ICU) admis- sion, mechanical ventilation, or death, among hospitalized children [1].

A potentially life-threatening multisystem inflammatory syndrome (MIS-C) related to SARS-CoV-2 has emerged, with most children

https://doi.org/10.1016/j.ajem.2022.12.009

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requiring intermediate or intensive care [2-4]. This increased the de- mand for high intensity of care beds for COVID-19 patients, putting under pressure Hospital resources and jeopardizing the care of acutely ill children who have not COVID-19. There was also a significant impact on complex surgeries needing ICU admission and a dramatic cost esca- lation. Children have been often admitted to pediatric ICUs not because of needing intensive care treatments but rather for monitoring, frequent and complex therapies, or concerns related to relevant comorbidities or young age. These patients who need monitoring and treatment beyond what can be offered in a general hospital ward but do not qualify for pediatric ICU admission may be more appropriately cared for in the intermediate care unit (IMCU) [5].

IMCUs are not a new concept but defining their role in pediatrics is difficult due to the considerable variations in definitions and care delivery [6,7].

In the last decades, advances in pediatric medical, surgical, and critical care have resulted in an evolution in the acuity and complexity of children potentially requiring IMCU admission, as well as increased survival of children with complex chronic diseases, emphasizing the need for IMCU development.

However, research evaluating pediatric IMCUs and data on their operation is very limited.

The present paper aims to report on the activity of a newly estab- lished COVID-19 pediatric IMCU in an Italian tertiary children’s hospital, retrospectively analyzing its impact on the management of patients with SARS-CoV-2-related illness.

1. Materials and methods
   1. Setting

IRCCS Gaslini is a tertiary care [8] freestanding children’s hospital with a level 1 pediatric trauma center [9], serving a region of 1.5 million inhabitants in the North West of Italy, but with a catchment area ex- tended to the whole Nation and many European and foreign countries for highly specialized medical and surgical pediatric care. The hospital has 328 pediatric beds, and it is equipped with an 18-20 beds-level IV pediatric ICU [10] with critical care transport and extracorporeal mechanical oxygenation (ECMO) retrieval capability.

At the beginning of the pandemic, the hospital was identified as the hub for all SARS-CoV-2-positive pediatric patients needing hospitaliza- tion in the Region.

• 1. Infrastructure and equipment

Two units were assigned to the care of COVID-19 patients: a 10-bed unit in the Infectious Disease ward for low-intensity care patients and a

respiratory support, a dedicated system for point-of-care ultrasonogra- phy, and Personal protective equipment . Isolation procedures have been reinforced.

• 1. Staff

The IMCU functions as a standalone unit collocated adjacent to the pediatric ICU. Seven physicians cover the IMCU 24/7, two of them at once daily (8 a.m. – 8 p.m.), and one during the night (8 p.m. – 8 a.m.). All clinicians in the IMCU are pediatric emergency medicine specialists, with extensive experience in the treatment of severely ill children in the Emergency Department (ED) and with a master’s degree in pediatric intensive care. As for the medical team, a new nursing team was assembled. Four nurses are present on day shifts and three at night, with a variable 1:3-1:4 nurse-to- patient ratio. The head nurse came from the PICU and provided all the necessary training and supervision with the aid of a senior nurse with an emergency medicine background.

• 1. Criteria of IMCU admission and discharge

Criteria for IMCU admission and discharge for patients with COVID-relatED diseases were designated with input from multiple stakeholders referring to previously published guidelines for pediat- ric IMCUs [5] and are shown in Table 1. However, in consideration of the increasing awareness of the effects of SARS-CoV-2 infection in pediatrics, the criteria have been adapted to the evolving pandemic scenario.

Children were considered for transfer to low-intensity care units when clinically stable, i.e. when the need for continuous monitoring or multiple disciplinary intervention and treatment were no longer needed.

However, to keep microbiological segregation, transfers to low- intensity care units were restricted and some patients had to be managed in IMCU until their discharge.

The IMCU was available for the rest of the children requiring inter- mediate care but not affected by SARS-CoV-2-related diseases.

These subjects underwent a strict microbiological surveillance policy with SARS-CoV-2 nasopharyngeal swabs performed at the hospital ad- mission, in case of subsequent appearance of suspicious symptoms, and routinely every week.

Table 1

Criteria for pediatric Intermediate Care Unit admission and transfer/discharge of children with SARS-CoV-2 related disease

newly designed 12-bed IMCU for those needing intermediate care. Both

units are equipped with single rooms with an anteroom, all with HEPA filters, and in 7 of them, there is the possibility to create negative pres- sure. Admission to negative-pressure rooms was primarily reserved for

patients with a high risk of transmission as those requiring ventilation

IMCU admission IMCU transfer/discharge

Neonatal age Stability of hemodynamic parameters for at least 48 h

Moderate/severe prematurity No oxygen requirement

support.

One parent is allowed to care for the child 24/7 in the room and has

Relevant pre-existing disease or medical complexity with high risk of deterioration

Neurological stability with seizures control for at least 48 h

his bed.

In IMCU all rooms have a multiparameter monitor connected to a

Need for respiratory support No record for cardiac arrhythmia for at

least 72 h

control station located in the nurse’s room and could be transformed into an ICU room in case of patients’ worsening, escalating care up to

Seizure/ acute inflammation or infection of the central nervous system/ Altered sensorium

Return to baseline clinical status for patients with medical complexity or relevant pre-existing condition.

ECMO. In this case, the ICU medical and nursing staff took over the lead-

ership, bringing all the necessary materials (e.g., ventilators, ECMO pumps, hemodialysis systems) without moving the patient.

The IMCU was previously a general pediatric ward with single or double-bed rooms, all equipped with anterooms, oxygen, air, and suctioning sources. In terms of equipment, the IMCU was provided with emergency carts, a point-of-care Blood gas analyzer, centralized monitoring for each room, infusion pumps, devices for non-invasive

electrolyte imbalance Management complexity compatible with policies of the receiving unit

Any sign of cardiac involvement and/or need for EKG monitoring

Hypotension/need for non-invasive blood-pressure monitoring

Acute renal failure with no need for continuous replacement therapy

Need for diuresis monitoring

• 1. Data selection

For the descriptive purposes of this study data retrieved regarded demography, clinical features, laboratory, radiological, and cardiologic exams, therapies, and outcomes of all patients aged 0-18 years with SARS-CoV-2 infection or who received a diagnosis of MIS-C according to CDC and WHO criteria [11,12], admitted to Gaslini IMCU from March 1, 2020, to January 31, 2022.

This study was reviewed and approved by the Regione Liguria Ethical Board (IRB# 370/2020).

1. Results

During the study period, 550 patients were hospitalized for acute COVID-19 or MIS-C at Gaslini Hospital (518 with acute COVID-19 and 32 with MIS-C).

Table 2 reports on Demographic and clinical data of 106 (19.2%, 80 with acute COVID-19 and 26 MIS-C) patients admitted to the ICMU directly from the ED or transferred from other lower-intensity care hospital units for Clinical worsening or increased concern: 39% of them had at least one chronic medical condition, neurological diseases being the most represented. The median age was 4 years and 30% had

<12 months of age. The median length of stay in ICMU was 6 days.

Twenty children (19%) needed respiratory support, which was mostly represented by low or high-flow oxygen supplementation. Two patients (2%) required non-invasive ventilatory support. Eight patients (8%), all diagnosed with MIS-C, presented with hypotension or shock with evidence of mild to severe left ventricular dysfunction on echocardiography.

Forty-one patients (39%) received immunomodulatory treatment (immunoglobulins, steroids, anakinra, or a combination). According to our internal protocol [13], anakinra was given to 9 patients with MIS-C and 2 with severe COVID-19 pneumonia.

Three patients (2.8%) needed escalation to intensive care, which was provided in the same room in collaboration with the critical care team. Two patients with acute COVID-19 (one 14-year-old obese girl with severe pneumonia and one 4-month-old boy with pneumonia and staphylococcal sepsis) developed Acute respiratory distress syndrome and needed emergency intubation and mechanical ventilation. One patient with MIS-C presented with cardiogenic shock requiring inotropic support and Invasive blood pressure monitoring. Two other patients with severe COVID-19 pneumonia and relevant comorbidities (a 10-year-old girl with adenosine-deaminase 2 deficiency and a 2-year-old boy with neuroblastoma) needed immediate critical care for mechanical ventilation. They were admitted into the IMCU, as the COVID unit, although they have been cared for by pediatric ICU special- ists, equipping the IMCU room as an ICU room. The girl subsequently died despite ECMO support [14].

Forty-seven patients (44%) were directly discharged from the ICMU, while the remaining 57 (55%) were transferred to low-intensity care units after clinical improvement.

Fig. 1 shows the hospital distribution and flow of patients.

In the same period, a total of 917 patients with no COVID-related diseases were managed in IMCU, and 59 (6.4%) required admission to the ICU.

No cases of SARS-COV-2 infection during hospital stay were detected among IMCU patients affected by non-COVID-related disease.

1. Discussion

The SARS-CoV-2 pandemic has had devastating social and economic consequences. Throughout the pandemic, several health systems were overwhelmed and required profound reorganization.

Although within the first phase of the pandemic, SARS-CoV-2 infec- tion was initially considered a mild disease in pediatrics, some children can experience severe COVID-19-related ARDS, requiring advanced

Table 2

Key features of children with COVID-19-related disease treated in the IMCU of Gaslini

Institute
	Total, n (%)
Characteristic	106 (100)
Age, median (range), years	4 (0-18)
< 1 year	32 (30)
1-4 years	23 (22)
5-9 years	13 (12)
10-18 years	38 (36)
Sex, female	54 (51)
Pre-existing conditions	41 (39)
Neurology	18 (17)
congenital heart disease	11 (10)
Respiratory	12 (11)
Immunosuppressed/
Oncology/Hematology	6 (6)
Obesity	7 (7)
Others	10 (9)
Clinical features
Fever	85 (80)
Cough	27 (25)
Respiratory distress	19 (18)
Abdominal pain	17 (16)
Hypotension/Shock	7 (7)
Seizures	6 (6)
Acute renal failure	1 (1)
Laboratory testing on admission, median	92 (87)
White blood count, el/ uL (IQR)	9410 (5710-12,030)
Lymphocytes, el/ uL	1990 (805-2870)
Haemoglobin, g/dL	12,2 (11,2-13)
Platelets, 103/uL	250 (175-342)
C-reactive protein, mg/dL	4,25 (1,29-12)
Pro-Brain Natriuretic Peptide, pg/mL	908,4 (182-2356)
D-dimer, mg/L	1,91 (1,2-3,6)
Ferritin, ng/mL	285 (89-521)
Respiratory support	20 (19)
Low-flow oxygen	9 (8)
high-flow nasal cannula	9 (8)
non-invasive ventilation	2 (2)
Chest imaging	52 (49)
X-ray	50 (11)
– Pathological	35 (33)
Parenchymal thickening	17 (16)
Interstitial pneumonia	24 (23)
Pleural effusion	9 (8)
Computed tomography	9 (8)
– Pathological	9 (8)
EKG	43 (41)
EKG abnormalities	30 (28)
– Left ventricular dysfunction – Bradycardia	9 (8)
– Tachycardia	7 (7)
– long QT	12 (11)
– AV block	1 (1)
– ST abnormalities	11 (10)
– Others	16 (15)
Echocardiography	38 (36)
Echo abnormalities	30 (28)
– Left ventricular dysfunction	8 (8)
– Coronary abnormalities	16 (15)
– Valvulopathy	14 (13)
– Pericarditis	7 (7)
Outcome
Discharge	47 (44)
Transfer to Low Intensity	55 (54)
Transfer to Pediatric Intensive care unit	3 (3)
Medication
Steroid	38 (36)

Table 2 (continued)

Total, n (%)

Although not assessed in the current study, the low rate of ICU ad- mission may have favored better beds utilization by preventing ICU

overcrowding, considering the spread of the SARS-CoV-2 variants and

Immunoglobulin 27 (25)

Heparin/acetylsalicylic acid 38 (36)

Remdesivir 3 (3)

Antibiotic 41 (39)

Monoclonal antibodies 1 (1)

Anakinra 11 (10)

respiratory support (i.e., mechanical ventilation and ECMO), or develop previously unknown complications, such as MIS-C (2) with life- threatening conditions and long-term consequences [4].

According to different studies, the rate of pediatric ICU admission for patients with acute COVID-19 ranged from 3,5% to 30%and higher in the case of MIS-C (60%-80%) [1,3,4,15-19].

Introducing a new IMCU in our hospital and the consequent hospital reorganization resulted in a very low rate of ICU admissions (0,9%).

The need for ICU admission, including those children who required an escalation of care from ICMU to ICU, was low for both acute COVID- 19 patients (0.8%) and MIS-C patients (3.8%).

In our hospital, the IMCU represented an adequate setting to take care of COVID-19 children with known risk factors for severe disease (primarily young age and pre-existing medical conditions) and substan- tial Health care needs, but not requiring critical care.

In our series, only 19% of our patients needed respiratory support thus suggesting possible inappropriate admissions to IMCU. However, our Institute is equipped with all main pediatric subspecialties and takes care of many children with chronic diseases and medical complex- ity. This population accounted for a significant part of IMCU admissions, following the great concern related to SARS-CoV-2 infection, the need for Close monitoring, and the complexity of therapies and nursing care. Regarding MIS-C, we hypothesize that our favorable outcome was at least in part related to our integrated multidisciplinary approach driven by the expertise of rheumatologists, cardiologists, and infectious disease specialists, and centered on the presence of the IMCU with the prompt support of critical care physicians when needed. This allowed a timely and multi-step treatment modulated on disease severity [13]. All MIS- C patients with signs of cardiac involvement and need for close Clinical monitoring were initially admitted to IMCU until clinical stability was achieved and then transferred to rheumatology or cardiology units

until discharge.

the broad vaccination coverage, which increased in the last months the rates of SARS-CoV-2 infection in unprotected children younger than 5 years [20].

Despite all the efforts for child and family-centered intensive care, inappropriate pediatric ICU admission exposes children to stressful ex- periences with potential long-term psychological burdens [21]. Mitigat- ing these effects is increasingly recognized as a core objective of critical care, and the role of a pediatric IMCU may be crucial. Close integration between IMCU and ICU allows flexible personnel and bed utilization with a nursing skill mix optimizing patient care. Even if pediatric IMCU and ICU are physically separate in our hospital, they are adjacent and located on the same floor. Our organization allowed a timely esca- lation from intermediate to critical care in the IMCU without the need for patient transfer.

Another strength of our organization was the absence of nosocomial spread of SARS-CoV-2 infection to unaffected patients both in the IMCU and the rest of the hospital, as shown in previous articles. [22,23].

Although not universally defined, the need for pediatric ICMUs has been increasingly recognized even in the pre-pandemic era [24]. How- ever, during the last decades, their development process has been largely incomplete, with significant disparities across countries, both in terms of bed recruitment and organizational models. Furthermore, adequate codification and valorization have not been identified for the care activities carried out in pediatric IMCUs.

Many factors contribute to variations among different countries: dif- ferent definitions of high-dependency care, resources, staff training and competencies, bED capacity, funding models, and interplay with local pediatric ICUs. This may limit rigorous scientific studies.

Recently, the American Academy of Pediatrics has set a policy state- ment to provide enhanced guidance for institutions, administrators, and providers in the development of a pediatric IMCU [25].

1. Conclusions

Although not easily generalizable to other institutions and differ- ent healthcare systems, we believe our experience may support a more functional and child-tailored organization of high-level pediatric care.

Fig. 1. Location of care and COVID-related patients flow within the Gaslini children’s hospital.

Further studies are needed to better assess the effects on hospital costs, pediatric ICU workload, and bed utilization, as well as the impact on psychological sequelae among children and their families.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

CRediT authorship contribution statement Giacomo Brisca: Writing – review & editing, Writing – original draft,

Validation, Conceptualization. Giacomo Tardini: Writing – original

draft, Methodology, Formal analysis, Data curation. Daniela Pirlo: Visualization, Investigation. Marta Romanengo: Writing – review & editing, Visualization. Isabella Buffoni: Investigation, Data curation. Marisa Mallamaci: Investigation, Data curation. Valentina Carrato: Investigation, Data curation. Barbara Lionetti: Investigation, Formal analysis, Data curation. Marta Molteni: Investigation, Formal analysis, Data curation. Elio Castagnola: Writing – review & editing, Validation. Andrea Moscatelli: Writing – review & editing, Supervision, Conceptualization.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influ- ence the work reported in this paper.

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