Journal of Clinical and Scientific Research

ORIGINAL ARTICLE
Year
: 2022  |  Volume : 11  |  Issue : 3  |  Page : 162--166

A retrospective analysis of characteristics and perioperative outcomes of rhino-orbital-cerebral mucormycosis in COVID-19 patients posted for surgical debridement under general anaesthesia in a tertiary care hospital


KG Sreehari1, T Jamuna1, Sreenivas Gouripeddi2, N Sunil1, C Venkataramanaiah1,  
1 Department of Anaesthesia, Sri Venkateswara Medical College, Tirupati, Andhra Pradesh, India
2 Department of Otorhinolaryngology, Sri Venkateswara Medical College, Tirupati, Andhra Pradesh, India

Correspondence Address:
K G Sreehari
Assistant Professor, Department of Anaesthesia, Sri Venkateswara Medical College, Tirupati 517 507, Andhra Pradesh
India

Abstract

Background: Rhino-orbital-cerebral mucormycosis (ROCM) has increasingly been reported in patients with severe acute respiratory syndrome coronavirus disease-2019 (COVID-19) from India. Methods: A retrospective study was done to analyse the demographic and clinical characteristics, treatment received for COVID-19 during the hospital stay, perioperative outcomes in ROCM patients posted for surgical debridement under general anaesthesia from May 2021 to July 2021 at our tertiary care teaching hospital in Tirupati, southern India. Results: Overall, 350 patients with ROCM and COVID-19 had undergone surgical debridement under general anaesthesia Mucormycosis was predominantly seen in males (65.7%). Majority of the cases (40%) were in the age group between 41-50 years. Common comorbidities were: pre-existing diabetes mellitus (DM) (70%), hypertension (32%), new-onset DM/hyperglycaemia (22%) and cardiac disease (8%). The most common sites involved in mucormycosis were the nose and paranasal sinuses (100%) followed by rhino-orbital (63.1%). A history of hospital admission for COVID-19 management was evident in 89.7%; 40.7% of the patients had received oxygen therapy during their hospital stay. The use of corticosteroids for the treatment of COVID-19 was noted in 73.2%. The types of surgical procedures done were: functional endoscopic sinus surgery (FESS) (98.5%) and neurosurgery procedures (3.4%). Revision surgery was performed in 18.5% of the cases. Perioperative complications observed were anticipated difficult intubation during pre-operative airway assessment 35.7%, intraoperative hypertension 8.5%. A patient had developed intraoperative cardiac arrest, post-operative-delayed recovery and needed ventilator requirement. Outcomes of ROCM patients associated with COVID-19 were: discharged 91.7%, death 8.3%. Conclusions: Diabetes mellitus, rampant use of corticosteroids in the treatment of COVID-19 appear to have contributed to the development of ROCM. Early diagnosis, a thorough pre-operative evaluation, surgical debridement are likely to result in better prognosis in COVID-19 patients with ROCM.



How to cite this article:
Sreehari K G, Jamuna T, Gouripeddi S, Sunil N, Venkataramanaiah C. A retrospective analysis of characteristics and perioperative outcomes of rhino-orbital-cerebral mucormycosis in COVID-19 patients posted for surgical debridement under general anaesthesia in a tertiary care hospital.J Clin Sci Res 2022;11:162-166


How to cite this URL:
Sreehari K G, Jamuna T, Gouripeddi S, Sunil N, Venkataramanaiah C. A retrospective analysis of characteristics and perioperative outcomes of rhino-orbital-cerebral mucormycosis in COVID-19 patients posted for surgical debridement under general anaesthesia in a tertiary care hospital. J Clin Sci Res [serial online] 2022 [cited 2022 Oct 2 ];11:162-166
Available from: https://www.jcsr.co.in/text.asp?2022/11/3/162/350736


Full Text



 Introduction



Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with a wide range of opportunistic bacterial and fungal infections. Fungal spores are copious in the atmosphere. Normally, inhaled fungi form a part of the normal sino-nasal flora, but they are significantly destroyed by the immunological system. However, in conditions such as widespread use of steroids/monoclonal antibodies/broad-spectrum antibiotics as part of the armamentarium against COVID-19, poor ventilation and moist environment as well as immunocompromised patients, these immunological pathways may be disrupted, making fungal invasion more likely to make a morbid affection of tissues.[1]

Acute invasive fungal sinusitis is considered the most aggressive form of sinusitis. Furthermore, it is as a rule with sudden critical advancement of nasal congestion, facial pain, epistaxis and fever. Expansion into the sinus or intracranial compartments can lead to neurological impairments.[2]

Mucormycosis is an angioinvasive disease caused by mould fungi of the genus Rhizopus (most common), Mucor, Rhizomucor, Cunninghamella and Absidia of Order Mucorales, Class Zygomycetes.[3],[4] The mean duration between the diagnosis of COVID-19 and the development of symptoms of mucormycosis was 15.6 ± 9.6 days.[5]

The primary reason that appears to be facilitating Mucorales spores to germinate in patients with COVID-19 are: hypoxic environment, high blood glucose levels (DM, new-onset hyperglycaemia and steroid-induced hyperglycaemia); acidic medium (metabolic acidosis and diabetic ketoacidosis [DKA]); high serum iron levels; endotheliitis, endothelial damage and thrombosis; and immune dysregulation, reduced T-lymphocytes and decreased phagocytic activity of white blood cells (WBC) due to immunosuppression (SARS-CoV-2–mediated, steroid-mediated or background comorbidities).[6]

Globally, the prevalence of mucormycosis varied from 0.005–1.7/million population, while its prevalence is nearly 80 times higher (0.14/1000) in India compared to developed countries, as per a recent estimate.[7] DM remains the leading risk factor associated with mucormycosis globally, with an overall mortality of 46%. Indeed, the presence of DM was an independent risk factor (odds ratio 2.69; 95% confidence interval 1.77–3.54; P < 0.001) in a meta-analysis[8] of 851 cases of rarely occurring mucormycosis. While long-term use of corticosteroids has often been associated with several opportunistic fungal infections including aspergillosis and mucormycosis, even a short course of corticosteroids has recently been reported to link with mucormycosis, especially in people with DM.[9]

Guidelines in India recommended intravenous (iv) methylprednisolone 0.5–1 mg/kg/day for 3 days in moderate cases and 1–2 mg/kg/day in severe cases.[10] The National Institute of Health recommends the use of dexamethasone (6 mg/day for a maximum of 10 days) in patients who are ventilated or require supplemental oxygen but not in milder cases.

The fatality rate with mucormycosis is pretty high. Especially the intracranial involvement of mucormycosis increases the fatality rate to as high as 90%.[1] The present was designed to describe the data related to demographic, clinical characteristics; and perioperative complications and outcomes of ROCM patients posted for surgical debridement under GA.

 Material and Methods



After obtaining Institutional Ethics Committee approval (L. No. 154/2021, dated 31 July 2021), we retrospectively reviewed medical records of all ROCM patients associated with COVID-19 infection posted for surgical debridement under general anaesthesia during the period from May 2021 to July 2021 (3 months) in the Department of Anaesthesiology, Sri Venkateswara Ramnarain Ruia Government General Hospital, the tertiary care teaching hospital attached to Sri Venkateswara Medical College (SVMC), Tirupati, Andhra Pradesh, India.

Patients who were aged >18 years and ROCM patients associated with COVID-19 (recovered), posted for surgical debridement under general anaesthesia from May 2021 to July 2021 were included. ROCM patients with active COVID-19 infection confirmed by positive real time–polymerase chain reaction (RT-PCR) at the time of admission for surgical debridement and patients who had undergone ROCM surgeries done under local anaesthesia were excluded.

A negative RT-PCR report was documented, before taking up the patients for surgery. Regarding pre-operative evaluation, we screened the case records of patients for post-COVID pulmonary and cardiovascular residual dysfunction. The peripheral oxygen saturation was checked. Complete biochemical workup of renal functions, serum electrolytes and coagulation profile was done in all patients. Optimisation of blood glucose levels including switchover to insulin was done. Heparin is withheld before surgery and restarted postoperatively. The decision to stop or continue oral anticoagulants was taken after a multidisciplinary discussion. Written informed consent for surgery had been obtained from all patients. The patients were kept fasting overnight and received tablet ranitidine 150 mg orally as pre-medication at night before surgery.

The surgical debridement procedures performed are functional endoscopic sinus surgery FESS, maxillectomy, exenteration, palatal debridement, craniotomy, among others. The difficult airway cart was kept ready because patients can have airway oedema, restricted mouth opening due to jaw erosion and pain, palatal ulcers which bleed on touch, palatal perforations and crusts in the nose, oroantral fistulas and DM-induced joint stiffness. Facial swelling, proptosis and perioral wounds due to the use of tight-fitting non-invasive ventilation masks during COVID-19 treatment can hinder mask ventilation.

All patients were monitored with electrocardiography, pulse oximetry and non-invasive blood pressure. Pre-oxygenation was done for 3 min and after securing an intravenous (IV) cannula, patients were induced with IV glycopyrrolate 0.2 mg, midazolam 0.05 mg/kg, propofol 2–2.5 mg/kg or ketamine 2 mg/kg (for unstable patients), fentanyl 2 μg/kg and suxamethonium 2 mg/kg body weight. Following laryngoscopy, an appropriate size endotracheal tube was secured and a throat pack was inserted.

Maintenance of an adequate mean arterial pressure (60–70 mmHg), cardiac output and normovolaemia are of paramount importance. Anaesthesia was maintained with oxygen: nitrous oxide (50:50) and sevoflurane (1%-2%). Muscle relaxation was maintained with IV atracurium. On completion of the surgery, reversal was achieved with IV neostigmine 0.05 mg/kg and IV glycopyrrolate 0.01 mg/kg. After adequate recovery, patients were shifted to post-operative ward for monitoring. Intraoperative hypertension was defined as increase in systolic blood pressure >20% from baseline reading.

Patients with delayed recovery and unstable patients were shifted to post-operative intensive care unit (ICU) for ventilator support. Post-operative ICU care was also required for patients with multiple comorbidities, post-COVID-19 respiratory problems and airway-related issues.

Statistical analysis

Data regarding demographic characteristics (gender and age) and clinical characteristics which include the type of comorbidities, treatment received for COVID-19, site of involvement and types of surgical procedure undergone by each patient were recorded. Data regarding the incidence of perioperative complications which include difficult airway, intraoperative hypertension, cardiac arrest and post-operative ventilator requirement and outcomes (discharged well, discharged against medical advice [DAMA] and death) of each patient were recorded. Data regarding demographic, clinical characteristics and the incidence of perioperative complications and outcomes in ROCM patients posted for surgical debridement under general anaesthesia were collected from medical records on an excel sheet and analysed independently by two investigators for accuracy. Data are presented as numbers and percentages. 'Worst case scenario' analysis was undertaken where all patients who have gone DAMA were considered to have died.[11] Statistical analysis was performed using the Statistical Package for the Sciences (SPSS), Version 23, IBM Corporation, New York, USA.

 Results



Overall, 350 patients with ROCM and COVID-19 had undergone surgical debridement under GA. Mucormycosis was predominantly seen in males (65.7%). Majority of cases were observed in the age group between 41 and 50 years (40%) [Table 1]. Common comorbidities are as follows: pre-existing DM was observed in 70% of the cases, hypertension in 32% of the cases, new-onset diabetes/hyperglycaemia in 22% of the cases and cardiac disease in 8% of the cases [Table 2].{Table 1}{Table 2}

The most common sites involved in mucormycosis were the nose and paranasal sinuses (100%), followed by rhino-orbital (63.1%) [Table 3]; 89.7% of the patients had history of hospital admission; 40.7% of the patients had received oxygen therapy during their hospital stay. The use of corticosteroids for the treatment of COVID-19 was recorded in 73.2% of the cases [Table 4]. Surgical debridement done under general anaesthesia and types of surgical procedures done are as follows: FESS 98.5%, maxillectomy 30.2%, palatectomy 19.4%, orbital exenteration 0.85% and neurosurgery procedures 3.42%. Twelve cases underwent neurosurgical debridement, of which two cases underwent frontal craniotomy and 10 cases underwent the endoscopic supraorbital eyebrow approach (minimally invasive) to remove extra and intra axial anterior skull base parasellar and frontal lesions. Revision surgery was performed in 18.5% of the cases [Table 5].{Table 3}{Table 4}{Table 5}

Perioperative complications observed were: anticipated difficult intubation during pre-operative airway assessment (MPG III and IV) 35.7%, intraoperative hypertension (defined as increase in systolic blood pressure >20% from baseline reading) 8.5%. One patient developed intraoperative cardiac arrest, post-operative-delayed recovery and required ventilator support [Table 6]. Twenty nine (8.3%) patients had died.{Table 6}

 Discussion



Mucormycosis is uncommon in healthy individuals. Pre-disposing conditions include uncontrolled DM with or without DKA, malignancies, organ transplantation, immunosuppressive and corticosteroid therapy, iron overload, deferoxamine therapy, open wound following trauma, severe burns, IV drug abusers and acquired immunodeficiency syndrome patients.[12]

Hyperglycaemia, acidosis, free iron and ketones in the presence of reduced phagocytic activity of WBC enhances the growth of Mucor. In addition, it also increases the expression of endothelial glucose-regulated protein 78 and fungal ligand spore coating homologue protein, enabling angioinvasion, haematogenous dissemination and tissue necrosis.[13]

In a multi-centre study[12] of 388 confirmed or suspected cases of mucormycosis from India before COVID-19, showed that 18% had DKA and 57% of the patients had uncontrolled DM. In a study[14] (n = 465 cases of mucormycosis without COVID-19) from India, rhino-orbital presentation was the most common (67.7%), followed by pulmonary (13.3%) and cutaneous type (10.5%). The pre-disposing factors include DM (73.5%), malignancy (9.0%) and organ transplantation (7.7%). In a prospective study,[15] before the COVID-19 pandemic had shown that the presence of DM increased the odds of contracting ROCM by 7.5 fold.

In a recent systematic review,[16] that had reported the findings of 41 confirmed mucormycosis cases in people with COVID-19, DM was observed in 93% of the cases and corticosteroids intake was found in 88% of the cases as risk factor.

These findings are consistent with our study (in data of 350 patients), mucormycosis was predominantly seen in males (65.7%). The majority of cases were observed in the age group between 41 and 50 years (40%). Pre-existing DM was found in 70% of the cases. The most common sites involved in mucormycosis are the nose and sinuses (100%) followed by rhino-orbital (63.1%). About 89.7% of the patients had a history of hospital admission for COVID-19 treatment. 73.2% of the cases received a course of corticosteroids. Better survival rates in our study may be due to early diagnosis and aggressive therapy with antifungal agents and surgical debridement.

The reported cases of mucormycosis may be an under-representation of the real burden due to difficulty in making a microbiological or histopathological or clinical diagnosis, especially in a pandemic situation. The majority of patients were COVID negative at the time of admission for ROCM, so no comparison could be done between patients with active COVID-19 and recovered cases. Data regarding, the duration of DM and baseline HbA1c for all diabetes patients were not obtained. Follow-up of these patients was not done.

An increase in mucormycosis appears to be a dreadful intersection of triad-DM, rampant use of corticosteroids and COVID-19 infection. Airway management, glycaemic control and respiratory compromise due to COVID-19 are the major challenges for anaesthesiologists. Early diagnosis and surgical debridement with a thorough pre-operative evaluation and optimisation of ROCM patients associated with COVID-19 results in better prognosis and survival rates.

Acknowledgement

We acknowledge the help and support of all the faculty and postgraduates in the Department of Anaesthesiology and Critical Care, Departments of Otorhinolaryngology, Ophthalmology, Neurosurgery, Biochemistry and Microbiology, Sri Venkateswara Medical College, Tirupati, Andhra Pradesh, India.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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