Successful Treatment of Severely Hypotensive Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) with the Guidance of Invasive Hemodynamic Monitoring: A Report of Three Cases

AUTHORS

Amir Saeed ORCID 1 , Nima Mehdizadegan ORCID 2 , *

1 Department of Pediatrics, Division of Pediatric Critical Care, Shiraz University of Medical Sciences, Shiraz, Iran

2 Cardiovascular Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

How to Cite: Saeed A, Mehdizadegan N. Successful Treatment of Severely Hypotensive Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) with the Guidance of Invasive Hemodynamic Monitoring: A Report of Three Cases. Arch Pediatr Infect Dis.In Press(In Press):e116282. doi: 10.5812/pedinfect.116282.

ARTICLE INFORMATION

Archives of Pediatric Infectious Diseases: In Press (In Press); e116282
Published Online: October 10, 2021
Article Type: Case Report
Received: May 21, 2021
Revised: August 22, 2021
Accepted: August 26, 2021
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Abstract

Introduction: Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak, it was assumed that infection rate in pediatric patients is lower than in adults and that infection is less severe in children than adult patients. Recently, there have been several reports and case series presenting critically-ill children with COVID-19, but still, severe hypotension is rare in pediatric patients with COVID-19.

Case Presentation: We describe three pediatric cases with COVID-19 who presented with multi-system organ failure and severe hypotension treated with the guidance of the parameters of an invasive continuous hemodynamic monitoring device. We also compare their parameters with few articles on pediatric sepsis parameters.

Conclusions: Although we usually start the treatment of hypotensive pediatric patients with hydration and epinephrine as an inotrope, in our cases, we required a different treatment plan according to the hemodynamic monitoring parameters, which indicates the value of the utilization of these devices in pediatric intensive care units

1. Introduction

In February 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) as a pandemic. This disease was first seen in Wuhan, China, with a group of people who had pneumonia with an unknown cause, and then coronavirus was detected in the respiratory samples of these patients (1) and named the virus severe acute coronavirus 2 (SARS-CoV-2) (2).

The first published data focused on adults as the rate of infection in children was low, and the infected had a milder disease. Although myocardial involvement was reported from the beginning of the pandemic in adult patients, it was believed that pediatric patients are infected with a milder disease. Nonetheless, after a while cases of critically-ill children with COVID-19 who presented with Kawasaki-like symptoms were reported; thus, the WHO set a new definition as “multisystem inflammatory syndrome in children (MIS-C)” (3).

According to the definition, MIS-C is seen in children and adolescents aged up to 19 years, with a history of > 3 days fever, evidence of COVID-19 (positive RT-PCR or serology) or contact with positive cases of COVID-19, and two of the following diagnostic criteria: mucocutaneous symptoms (e.g., rash or bilateral non-purulent conjunctivitis), cardiovascular disorders (hypotension), myocardial dysfunction (according to ECHO findings or elevated troponin/NT-proBNP), hematology abnormalities (increased PT, PTT, and d-Dimers), acute gastrointestinal symptoms (diarrhea, vomiting, or abdominal pain), and laboratory data indicating inflammation (e.g., increased ESR, C-reactive protein, or procalcitonin), and with the exclusion of bacterial sepsis, toxic shock syndrome, Kawasaki disease, and other diseases (3).

Hypotension is seen in severe cases of MIS-C; myocardial involvement due to direct viral invasion, acidosis, hypoxemia, pulmonary hypertension, cytokine storm, or septic shock resulting in hypotension are some supposed etiologies for this condition (4).

To approach a pediatric patient with septic shock; generally, clinical assessment according to extremity temperature, capillary refill time, and pulses and pulse pressure has been recommended to differentiate “warm” versus “cold” shock. Warm shock is defined as normal or increased cardiac output (CO) and low systemic vascular resistance (SVR), which is most often seen in adult patients. Cold shock is described with low CO and increased SVR (5), and according to the type of shock, different strategies for resuscitation are used (e.g., vasopressors for warm shock and inotropes for cold shock) (6), but in the latest guideline issued by Surviving Sepsis Campaign recommended using advanced hemodynamic parameters (if available), in addition to bedside clinical variables to guide the resuscitation of children with septic shock (7).

The monitoring of hemodynamic status was performed by an arterial line in the femoral artery, and the catheter of central venous line was inserted into the internal jugular or subclavian vein. Then, they were linked to pulse contour cardiac output (PiCCO), which is an invasive monitoring device. Pulse Contour Cardiac Output uses a combination of two methods for progressive hemodynamic and volumetric monitoring as follows: transpulmonary thermodilution for volumetric quantities of preload and C.O and pulse contour analysis to run constant C.O, cardiac index (CI), SVR, MAP, pulse pressure variation (PPV), stoke volume variation (SVV), etc. (8).

Although it is assumed that children contract a milder disease, still our knowledge about the aspects of this disease, especially the severe forms, is lacking. Herein, we described the cases of three girls with COVID-19 presented with multi-system inflammatory syndrome and severe hypotension, who were treated successfully with the guidance of parameters derived from a continuous invasive hemodynamic monitoring device.

2. Case Presentation

2.1. Case 1

A 10-year-old previously healthy girl was referred to the emergency room (ER) of her local town’s hospital due to prolonged fever, diarrhea, and lethargy. A week before hospital admission, she had fever and abdominal pain and received some medications, but her condition did not improve, and three days before admission, she developed diarrhea and her condition aggravated. Thus, she was taken to the hospital. In the ER, her vital signs were as follows: blood pressure (BP): 90/40, heart rate (HR): 135, and respiratory rate (RR): 32. On physical exam, she had bilateral non purulent conjunctivitis, cervical lymphadenopathy, strawberry tongue, and erythema of the hands. Thus, with the diagnosis of atypical Kawasaki disease, she was moved to our pediatric intensive care unit at Nemazee Hospital, in Shiraz (Nemazee Hospital is a tertiary hospital with 750 beds that is located in south of Iran and has an 18-bed medical PICU and a 9-bed surgery PICU). On arrival, her vital signs were: BP:55/30, HR:158, RR: 35, and Glasgow coma scale (GCS): 7/15. She was intubated and inotrope was started, and RT-PCR for COVID-19 with nasopharyngeal swab was sent for her, the result of which was positive. Laboratory data is listed in Table 1. Her clinical criteria fulfilled the criteria of MIS-C (Figure 1).

Table 1. The Initial Laboratory Data and Chest CT Scan Findings
Patient# 1Patient# 2Patient#3
Ferritin (ng/mL), M: 22.81 - 275, F: 4.63 - 204> 2000539
COVID realtime PCRPositivePositivePositive
Typical chest CT findingPatchy infiltrationBilateral patchy ground glassDiffuse and bilateral opacities
White blood cells (count/mL)25900330022000
Lymphocyte count9502601100
Procalcitonin, ≤ 0.314.289.91.8
C-reactive protein, < 6 (mg/L)15010530
Creatine phosphokinase (U/L), M: < 171, F: < 1453222470264
Lactate dehydrogenase (U/L), < 48066412401350
Troponin (ng/mL), < 1962.51163450
D-Dimer (ng/mL), < 50051932754638
Total bilirubin, 0.1 - 1.20.90.60.2
Direct bilirubin, < 0.30.50.20.1
Aspartate transaminase (U/L), M: < 37, F: < 315511497
Alanine aminotransferase (U/L), M: < 41, F: < 31374213
Albumin 2.82.92.5
Blood urea nitrogen (mg/dL), 8 - 20243053
Creatinine, M: 0.8 - 1.3, F: 0.6 - 1.20.814.8
Pt /INR17.1/1.2724.1/1.7917.9/1.33
Ptt 3231.935
Blood cultureNegativeNegativeNegative
ESR785448
Fibrinogen (200 - 400)426411580
Stool culture/urine cultureNegativeNegativeNegative
SCVO2789168

Echocardiography findings indicated borderline left ventricle function and dilated inferior vena cava (IVC) (it was performed while high-dose inotrope was infusing).

Arterial and central venous lines were inserted and connected to the PiCCO. According to the hemodynamic data (Table 2), inotropes (dopamine and epinephrine) were increased, and vasoconstrictor was started; in addition to parenteral hydrocortisone, ascorbic acid, and thiamine were administered (HAT protocol). Fortunately, the patient responded well, the inotrope was tapered and discontinued, and she was discharged in an acceptable state.

Table 2. The Initial PiCCO Parameters
Normal RangePatient#1Patient#2Patient#3
Sys BP (mmHg)727772
Dia BP (mmHg)434242
MAP (mmHg)535553
CI (L/min/m2)4.394.342.6
ITBI979680500
ELWI (cc/kg) (3 - 7)14611
GEDI (cc/m2) (680 - 800)420340332
SVRI (1700 - 2400)6905302240
PPV (%) (0 - 10)91211
SSV (%) (0 - 10)111722
PVPI (1 - 3)3.92.21.9

Abbreviations: CI, cardiac index; CE, cerebral edema; EVLWI, extravascular lung water index; MAP, mean arterial pressure; SVRI, systemic vascular resistance index; SVV, stroke volume variation.

2.2. Case 2

A 13-year-old girl was taken to the ER with the complaint of diarrhea, abdominal pain, and fever; three days before admission she presented with fever and abdominal pain, and on the day of admission, she presented with watery diarrhea. Her parents gave history that she had had up to 10 times watery diarrhea in the last hour, and she was taken to the hospital due to fecal incontinence. On arrival at the ER, vital signs were: BP: 110/65, HR: 152, RR: 22, and temperature: 40°C. She had GCS:13/15 and weak central pulses, so the infusion of dopamine was started, but due to the worsening of her condition (GCS dropped to 11 and BP to 90), she was intubated and transferred to the PICU (in ER, RT-PCR for COVID-19 with nasopharyngeal swab was taken, which showed positive results, and chest CT scan was done that was in favor of COVID-19).

Laboratory data (Table 1) and clinical signs and symptoms were in favor of MIS-C. In the PICU, C.V catheter was inserted, and epinephrine infusion was added. Echocardiogram revealsed poor left ventricle systolic function and borderline right ventricle systolic function with dilated IVC.

For constant hemodynamic observation, arterial line was placed into the femoral artery and connected to the PiCCO. According to low SVR, norepinephrine was started (HAT also was started) and titrated to acceptable MAP, and then vasopressin was added (the parameters are listed in Table 2).

Gradually, dopamine and epinephrine were tapered to discontinuation on day two, followed by norepinephrine and vasopressin. On the fifth day, she only received 0.2 µg/kg/min norepinephrine infusion, but due to severe ARDS, still, she needed mechanical ventilation till the 12th day that she was extubated and tolerated oxygen via non-rebreathing mask, and three days later she was transferred to the ward with a stable and acceptable condition.

2.3. Case 3

An 8-year-old girl was taken to the ER due to prolonged fever (four days), convulsion, and decreased level of consciousness (LOC). She also had a previous history of asthma.

On arrival to the ER: GCS:9/15, BP:85/40, HR:138, and RR:42 (laboratory data are listed in Table 1). The echocardiogram revealed fair left ventricle systolic function and moderate right pleural effusion. In the ER, her BP decreased to 55/20; thus, inotrope (dopamine) was started, and the patient was intubated and transferred to the PICU (RT-PCR for COVID-19 was positive).

In the PICU, she was connected to PiCCO with both arterial and C.V catheters; according to its data (Table 2), hydration and inotrope(epinephrine) were started. The inotrope was titrated, and the patient was extubated after four days. On the fifth day, inotrope was discontinued and the patient was discharged on the seventh day.

3. Discussion

In this report, we described successful treatment of three children with MIS-C and severe shock with the guidance of PICCO monitoring. This device defines our options for choosing inotropes or hydration for successful treatment.

Patients admitted to ICUs are at risk or have single or multiple organ failure. In such cases, we can use the traditional method: “HR, BP, central venous O2 saturation, central venous pressure (CVP), and urine output” or use the non-invasive or less invasive methods to direct our treatment (8).

Pulse contour cardiac output is a less invasive method with significant value when its variables are added to clinical variable in the right way and at the right time, and the patient has regular sinus rhythm and is fully sedated under controlled mechanical ventilation (6, 8, 9). In pediatric patients, intensivists typically treat septic shock with aggressive fluid administration and achieving the therapeutic goal of CI: 3.3 – 6.0 L/min/m2 (CI is generally low in pediatric septic shock with high SVR); in contrast to adult patients that have low SVR but CO is usually maintained or increased (6-10). As mentioned, we had a different plan for inotrope and hydration for each of our cases.

Acknowledgements

Footnotes

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