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Vol. 71. Issue 1.
Pages 79-83 (01 January 2021)
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Vol. 71. Issue 1.
Pages 79-83 (01 January 2021)
Case Reports
DOI: 10.1016/j.bjane.2020.10.009
Open Access
Helmet mask and tocilizumab for a patient with hemophagocytic lymphohistiocytosis syndrome and COVID-19: a case report
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Ahmet Eroglua,
Corresponding author
erogluah@hotmail.com

Corresponding author.
, Seyfi Kartalb, Ozlem Bayraktar Saralc
a Karadeniz Technical University, Department of Anesthesiology and Intensive Care Medicine, Trabzon, Turkey
b University of Health Science, Kanuni Training and Research Hospital, Department of Anesthesiology and Reanimation, Trabzon, Turkey
c Kanuni Training and Research Hospital, Department of Infection Disease, Trabzon, Turkey
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Table 1. Clinical progress of the patient.
Abstract

The management of acute hypoxemic respiratory failure and the effect of antiviral drugs in patients with severe COVID-19 have been debated. This case presents the management of a 64-year-old man COVID-19 patient admitted to the Intensive Care Unit with fever, fatigue, shortness of breath and hemophagocytic lymphohistiocytosis syndrome. Helmet mask was successfully used to treat his hypoxemic respiratory failure without any aerosol problems. Tocilizumab, an antagonist interleukin-6, was intravenously infused as an alternative drug. After administration, the high level of IL-6, CRP, ferritin, D-dimer, triglyceride, and H-scores decreased, and the patient observed good clinical and laboratory improvements. In this case report, we describe the effect of noninvasive ventilation delivered by helmet mask and antiviral drugs, and the intravenous administration of tocilizumab in a patient with hemophagocytic lymphohistiocytosis syndrome and COVID-19.

Keywords:
COVID-19
Helmet mask
Tocilizumab
H-scores
Hemophagocytic lymphohistiocytosis (HLH)
Full Text
Introduction

The management of acute hypoxemic respiratory failure and the effect of antiviral drugs in patients with severe COVID-19 have been debated. The clinical spectrum of COVID-19 varies from asymptomatic to requiring mechanical ventilation and advanced support in the Intensive Care Unit. Conventional oxygen therapy, oxygen mask with reservoir bag, HFNC, NIPPV, and invasive mechanical ventilation have been recommended to treat hypoxic respiratory failure in patients with severe COVID-19. The helmet mask, a transparent hood that covers the entire head of the patient with a soft collar neck seal, is used to treat acute hypoxemic respiratory failure in Acute Respiratory Distress Syndrome (ARDS)1 cardiogenic pulmonary edema,2 and hematological malignancy patients. A randomized clinical trial reported that noninvasive ventilation delivered by helmet mask reduced the rate of endotracheal intubation and improved other patient outcomes in ARDS patients.1

Antimalarial drugs like hydroxychloroquine, because of the potential antiviral effect, and some antiviral drugs such as favipiravir, remdesivir, and lopinavir/ritonavir have been tested in the treatment of patients with coronavirus disease. Tocilizumab, a known interleukin-6 blocker, can be used in the management of cytokine storms.3

In this case report we describe the effect of noninvasive ventilation delivered by helmet mask and antiviral drugs, and the intravenously administration of tocilizumab in a patient with hemophagocytic lymphohistiocytosis syndrome and COVID-19.

Case report

A 64-year-old man was admitted with fever, cough, fatigue, and shortness of breath on March 30, 2020. His medical history had hypertension, but no drug use. The diagnosis of COVID-19 was made after obtaining a chest tomography that showed bilateral multilobar ground-glass opacities, bilateral pulmonary infiltrates, and positive real-time PCR test for COVID-19.

In the Intensive Care Unit, the patient’s temperature was 38.7 °C, respiratory rate was 36 per minute, and oxygen saturation was 82. His heart rate and blood pressure were 88 per min and 130/80 mmHg, respectively. Oxygen mask with reservoir bag was applied as 4 L.min−1, and azithromycin for community-acquired pneumonia (500 mg orally on day 1, followed by 250 mg 1×/day on days 2–5), paracetamol for high fever (1000 mg intravenously 3×/day) were administered. Oseltamivir (75 mg 2×/day) was started because Influenza could not be ruled out, and hydroxychloroquine as a potential antiviral effect (400 mg orally 2×/day on day 1, then 200 mg 2×/day on days 2–5) was added to the treatment for 5 days. The close ECG including QT prolongation and hemodynamic monitoring of the patients was performed. The nasopharyngeal swab of the patient was cultured. Enoxaparin 40 mg subcutaneously 2×/day as an anticoagulant, acetylcysteine 100 mg 3×/day to loos mucus in the airways, vitamin C, and vitamin D were administered, and the patient’s nutrition was supplemented orally or parenterally on the ICU days. On day 4, because of tachypnea and decrease of oxygen saturation oseltamivir and azithromycin were stopped and favipiravir (1600 mg 2×/day on day 1, then 600 mg 2×/day on days 2–5), as an inhibitor of the RNA-dependent RNA polymerase and with potential antiviral effect, was added to the treatment for 5 days. Helmet mask was applied due to insufficiency of oxygen mask with reservoir bag. Patient tolerability to the helmet mask was good. When needed, we administered 2 mg of midazolam intravenously for patient sedation. On day 4 of the favipiravir, tocilizumab 400 mg was infused intravenously 2×/day for 2 days because of increased IL-6 levels and secondary hemophagocytic lymphohistiocytosis syndrome (H-Score > 169). After tocilizumab administration the high levels of IL-6, CRP, ferritin, D-dimer, triglyceride, and H-scores decreased (Table 1). On day 11 the patient showed good clinical and laboratory improvements, such as lower fever and higher oxygen saturation. On day 14 the patient was transferred to a negative COVID-19 service with better clinical condition and negative PCR test.

Table 1.

Clinical progress of the patient.

  At admission  Day 1  Day 3  Day 4  Day 8  Day 11  Day 14 
Fever (°C)  38.7  37.8  38.2  38.4  38.8  36.8  36.3 
Respiratory rate (per min)  36  26  24  34  32  14  12 
Ventilation support  Oxygen mask  OMRB  OMRB  Helmet mask  Helmet mask  Oxygen mask  Air room 
sPO2 (%)  82  92  76  96  98  98  96 
PO2 (mmHg)    68  43  72  84  82  78 
PCO2 (mmHg)    42  49  38  36  38  40 
PO2/FiO2    204  132  256  288  310  380 
Ph    7.32  7.25  7.30  7.36  7.34  7.42 
Bicarbonate (mmoL.L−1)(22–26)    24  26  18  30  22  22 
Laktat (mmoL.L−1)(0.5–1)    1,1  2,1  2,3  2,2  1,6  0.9 
Hemoglobin (g.L−1) (12–17)  12  11  10  11 
White-cell count (per mm3) (400−10,000)  2600  2500  2400  2200  3300  3800  4200 
Platelet count (per mm3)(100,000–400,000)  192,000  158,000  102,000  72,000  88,000  186,000  224,000 
BUN (mg.dL−1)(8–20)  24  26  28  30  25  20  16 
Creatinine (mmoL.L−1)(0.51–0.95)  092  093  1,1  1,4  1,2  096  084 
ALT (U.L−1)(0–35)  21  23  39  78  55  49  27 
AST (U.L−1)(0–35)  24  52  62  83  64  53  28 
Fibrinogen (mg.dL−1)(200–400)  320  280  160  120  140  220  340 
Ferritin (ng. mL−1)(11–306)  1400  2560  3400  4200  5800  1800  1200 
Triglycerides (mg.dL−1)(<130)  123  138  264  316  320  126  122 
INR(0.8–1.2)  1,2  1,3  1,5  1,7  1,6  1,5  1,3 
IL-6 (pg. mL−1)(0–6.4)    14  34  178  122  84  16 
CRP (mg.dL−1)(0–5)  78  104  136  265  138  82  11 
Troponin (ng.L−1)(0–11.6)  10 
D-dimer (mg.L−1)(0–500)  307  871  1839  1980  1873  1271  420 
H-score          195  73   
PCR  Positive      Positive      Negative 
DrugsPAR 3 × 1 g  PAR 3 × 1 g  PAR 3 × 1 g  FAVI 2 × 1600 mg, then 2 × 600 mgTCZ 2 × 400 mg IVENO 2 × 40 mgENO 2 × 40 mg
AZI 500 mg  AZI 4 × 250 mg  AZI 4 × 250 mg 
OSE 2 × 75 mg  OSE 2 × 75 mg  OSE 2 × 75 mg  ENO 2 × 40 mg  ENO 2 × 40 mg 
HCLQ 2 × 400 mg  HCLQ 2 × 200 mg  HCLQ 2 × 200 mg     
  ENO 2 × 40 mg  ENO 2 × 40 mg     

OMRB, Oxygen Mask with Reservoir Bag; PAR, Paracetamol; AZL, Azithromycin; OSE, Oseltamivir; HCLQ, Hydroxychloroquine; FAVI, Favipiravir; TCZ, Tocilizumab; ENO, Enoxaparin; iv, intravenous. (-) Normal range of a parameter.

Discussion

There is no specific treatment or therapy recommended for coronavirus disease 2019. The following therapeutic approaches can be suggested according to the severity of the disease, respectively: isolation, rest, fluid and food intake; oxygen support; respiratory treatment; anticoagulant treatment; hydroxychloroquine and combinations therapy; antiviral drugs (remdesivir, favipiravir, lopinavir/ ritonavir) and other immunomodulator drugs like tocilizumab; convalescent plasma therapy; mesenchymal stem cells therapy; and vaccination.

To our best knowledge, there is no trial comparing helmet mask and face mask or intubation for the management of acute hypoxemic respiratory failure in patients with severe COVID-19. We observed the helmet mask delivered higher airway pressures without substantial air leak. We did not observe any aerosol problems during the helmet mask applications. Healthcare workers wore the FFP3 (filtering face piece) mask under a standard surgical mask, and personal protective equipment during the applications. The helmet mask application has difficulties like patient tolerability, CO2 rebreathing, mask deflation, skin ulceration, gastric distention, eye irritation, and pain1,2 but the patient tolerated it well. When needed, we administered 2 mg of midazolam intravenously for sedation. As a result, a significant reduction in the respiratory rate and higher oxygen saturation levels were recorded. At the same time, the administration of the drugs against coronavirus, especially tocilizumab3 (with no contraindication) contributed to reduce the cytokine storm syndrome, or secondary Hemophagocytic Lymphohistiocytosis (sHLH).4

Hemophagocytic Lymphohistiocytosis (HLH) syndrome is a severe hyperinflammatory condition caused most commonly by viral infection in adults.5 Its cardinal clinical and laboratory features include fever, hepatosplenomegaly, hemophagocytosis, pancytopenia, hypofibrinogenemia, hyperferritinaemia, high triglycerides and liver enzyme levels. For the diagnosis of HLH syndrome, the H-scores should be over 169.4,5 In our case, the levels of ALT, AST, ferritin, triglycerides, CRP, D-dimer and IL-6 were elevated before the tocilizumab administration so we calculated the H-score was 195. After the tocilizumab intravenous infusion of 8 mg.kg−1, the levels of the mentioned parameters, and the calculated H-score were incrementally decreased (Table 1). Tocilizumab, an IL-6 receptor blockade, has been used in patients with severe COVID-19 presenting ARDS and elevated IL-6 levels.3 In our patient with severe COVID-19 and secondary HLH syndrome, we observed clinical improvements using the helmet mask without invasive mechanic ventilation and the tocilizumab administration.

Conclusion

Consequently, we suggest that all severe COVID-19 patients should be closely monitored for HLH syndrome, and the available anti-coronavirus drugs, especially tocilizumab, can be used early under noninvasive ventilation delivered by helmet mask.

Conflicts of interest

The authors declare no conflicts of interest.

References
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B.K. Patel, K.S. Wolfe, A.S. Pohlman, et al.
Effect of noninvasive ventilation delivered by helmet vs face mask on the rate of endotracheal intubation in patients with Acute Respiratory Distress Syndrome: a randomized clinical trial.
JAMA, 315 (2016), pp. 2435-2441
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J.M. Tonnelier, G. Prat, E. Nowak, et al.
Non-invasive continuous positive airway pressure ventilation using a new helmet interface: a case-control prospective pilot study.
Intensive Care Med, 29 (2003), pp. 2077-2080
[3]
C. Zhang, Z. Wu, J.W. Li, et al.
Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce the mortality.
Int J Antimicrob Agents, 55 (2020),
[4]
F. Debaugnies, B. Mahadeb, A. Ferster, et al.
Performances of the H-scores for diagnosis of hemophagocytic lymphohistiocytosiis in adults and pediatric patients.
Am J Clin Pathol, 145 (2016), pp. 862-870
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L. Fardet, L. Galicier, O. Lambotte, et al.
Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome.
Arthritis Rheumatol, 66 (2014), pp. 2613-2620
Copyright © 2020. Sociedade Brasileira de Anestesiologia
Idiomas
Brazilian Journal of Anesthesiology (English Edition)

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