Anesthesia Outcomes of Post-COVID Mucormycosis Surgery among Diabetics:A Retrospective Observational Study in India

Introduction

First case of Coronavirus disease 2019 was reported in December 2019 and has spread since then, leading to a pandemic that keeps challenging the medical field. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).¹ It presents with many twists and turns in its course as we try to understand the disease. After the second wave of COVID-19 pandemic, we have seen increase in reports of cases of mucormycosis in India.² According to the epidemiology of mucormycosis in India reported in 2021, the prevalence of mucormycosis is almost 70 times more than the worldwide data. Due to the steep rise in mucormycosis cases during the second wave of COVID-19 pandemic which was associated with severe complications and higher morbidity and mortality rate in post-COVID-19 patients, this rare disease is now notifiable in India.³

Diabetes mellitus (DM) which is prevalent worldwide has a significant role and impact on severe COVID-19 and mucormycosis.⁴ Severe COVID-19 pneumonia is associated with dysregulation of the immune system and cytokine syndrome leading to an increased use of immunomodulators.⁵ Thus, the conditions that appears to be facilitating spores to germinate in people with COVID-19 is a perfect environment of low oxygen (hypoxia), high glucose (diabetes, new-onset hyperglycemia, steroid-induced hyperglycemia), acidic medium (metabolic acidosis, diabetic ketoacidosis [DKA]), decreased phagocytic activity of white blood cells (WBC) due to immunosuppression (SARSCoV-2 mediated, steroid-mediated or background comorbidities), high iron levels (increased ferritins) and other risk factors including prolonged hospitalization with or without mechanical ventilation.⁴ The most common cause attributed to post COVID mucormycosis has been suspected to be uncontrolled diabetes, excessive use of corticosteroids and long-term stay in the Intensive care unit.

The second wave of COVID-19 was associated with a sudden rise in cases of mucormycosis in patients with COVID-19, especially in India.⁴ Globally, the prevalence of mucormycosis was 0.005 to 1.7 per million population, while it was nearly 80 times higher (0.14 per 1000) in India compared to developed countries, as per a recent estimate done in the year 2019-2020.^6,7 According to US Centre for Diseases Control and Prevention (CDC), the overall all-cause mortality rate of 54% was reported for mucormycosis. This mortality rate depends upon the general condition of the patient, fungus type, and affected site within the body. Despite disfiguring surgical debridement along with medical management, the overall mortality remains more than 50%, approaching 100% in patients with disseminated disease.⁸

In our study, we have observed the patients affected with post COVID mucormycosis posted for surgical debridement with/without orbital involvement concerning their anesthesia outcome.

Methods

A retrospective observational study was conducted (from May 2021 to June 2021) at our tertiary care center which was declared as a dedicated COVID hospital during pandemic. Data was collected from 60 patients (male & female) operated on for post-COVID mucormycosis. Adult patients of age ranging from 30 years to 70 years, known or recently diagnosed as diabetic in post COVID period, patients diagnosed with mucormycosis, with ASA II, III & IV E were included in the study. Pregnant patients, patients less than 30 years or more than 70 years of age were excluded.

Primary outcome of the study was to determine the percentage of patients extubated on operating table immediately after surgery while the secondary outcome was to estimate the morbidity and mortality due to COVID-19 mucormycosis in the form of patients shifted to ICU, requirement of invasive mechanical ventilation, postoperative complication within 48 hours if any.

Institutional ethical committee approval was obtained and confidentiality of the data was maintained throughout the study.

Sample size estimation was done using the formula:

where, Z = 1.96 at 5% level of significance p = the proportion of diabetics among Covid positives = 10%; q = 1-p = 100 – 10 = 90 d= absolute margin of Error taken as 8 %

Since it was a retrospective study, data could have been lost during collection. Considering this, along with a 10% non-response rate, the required sample size was calculated as a minimum of 54+6 = 60 subjects

Data was collected in a uniform, consistent and reliable manner by trained qualified doctors with the use of a standard proforma. Key variables as mentioned in data collection tool were documented. Data from the postoperative period till 48 hours was also collected and the outcome was analysed. 

Results

As shown in table 2, out of 60 subjects included, 70% of the patients affected with COVID mucormycosis were males, out of which majority of patients were in the age group of 60-69 years (31.67%) while 26.67% patients were in the age group of 50-59 years and 21.67% patients were in the age group 40-49 years. There were 11.67% patients in the age group 30-39 years and only 5 patients (8.33%) were above 70 years of age. Out of all the patients operated for COVID mucormycosis, 49 patients (81.67%) had history of Diabetes mellitus as shown in table 2, out of which 20 patients were recently diagnosed with diabetes mellitus (HbA1c >6.5) in post COVID period. Other co-morbidities commonly observed in these patients were hypertension (11.67%) and asthma (3.33%) (Table 2).

Chest X-ray was done for all the patients on admission. Thirty six patients (60%) showed lung infiltration, of which 10 patients had left-sided involvement, while four patients had right-sided lung involvement. Bilateral lung involvement in the form of fibrosis was found in three patients (5%). 35% of patients showed normal chest X-ray findings. Mean SpO2 was found to be 96.39. Only 15% of patients had saturation levels below normal values.

Out of 60 patients studied, 59 patients (98.33%) were extubated postoperatively on the operating table. Only one patient could not be extubated immediately on the table due to inadequate tidal excursions, with the requirement of inotropic support intraoperatively, and was shifted to the critical care unit on mechanical ventilation. All the patients were monitored for 48 hours postoperatively for any complications. None of the patients had complications in the form of ARDS or ALI. Mortality was 1.67% and was due to respiratory failure in the postoperative period in a patient with uncontrolled Diabetes mellitus for 20 years.

Discussion

Not many studies have been conducted discussing anesthesia outcomes in patients suffering from mucormycosis in the post-COVID-19 period. Type 2 Diabetes Mellitus is the leading cause of morbidity and mortality among non-communicable diseases.⁹ It also contributes to the high risk and worsened outcomes of infections. Diabetes mellitus is a major risk factor associated with mucormycosis in India.¹⁰

Majority of population in India does not undergo regular health checks and mucormycosis was reported as a diabetes defining illness in 23- 43% of patients in multiple publications.¹⁰

In a study conducted by Singh et al, pre-existing Diabetes mellitus was observed in 80% of patients.⁴ In our study, 81.67% of patients were suffering from Diabetes mellitus out of which 20 patients were recently diagnosed in post COVID period with HbA1c values more than 6.5%. Other risk factors included hypertension and asthma comprising 11.67% & 3.33%, while 16.67% of patients had no significant coexisting diseases.

When looking at the demographics of COVID-19 patients affected with mucormycosis, 31.67% of patients were in the age group of 60-69 years, 26.67% patients were in the age group of 50-59 years. 11.67% of patients belonged to age group 30-39 years which was an unexpected finding.

In the study conducted by Singh et al, mucormycosis was predominantly seen in males (78.9%), both in people who were in active phase (59.4%) or recovered (40.6%) from COVID-19.4 In our study, 70% of affected patients were males while 30% were females.

Mucormycosis developed in most of the patients while they were recovering from active COVID-19 infection; therefore even the lungs of these affected patients were in recovery stages. 60% of patients in the present study had lung involvement in the form of infiltration and 35% of patients had normal chest X-ray findings as compared to active COVID-19 infection where ground-glass opacity was the most common pattern in chest imaging.¹

Mucormycosis patients with soft tissue involvement require early management and surgical debridement. Surgery alone may not be curative, but an aggressive surgical approach has been shown to improve survival.^11,12 Also, the liposomal Amphotericin B remains the antifungal of choice which is associated with side effects like nephrotoxicity, hypotension, hypokalemia, hypomagnesemia, arrhythmias, and fever that pose a challenge to anesthetic management. Even with aggressive medical and surgical management, prognosis remains poor, with reported mortality rates of 33.3–80 percent, approaching up to 100 percent in disseminated infections.¹²

Multiple factors including post-COVID systemic effects like residual pulmonary dysfunction, adrenal suppression, myocardial dysfunction, difficult airway due to mucormycosis,¹³ and adverse effects of Amphotericin B (AmB) can alter the anesthesia outcome in these patients.¹⁴ We considered all these and optimized patients accordingly for anesthesia. Thus, 98.33% of patients were extubated postoperatively on the table. The mortality rate was 1.67% in our study.

Even though preoperative optimization is ideal, in our study, intraoperative optimization of hyperglycemia and electrolyte derangement were done because of the emergency nature of surgery as mucormycosis is a rapidly spreading disease and early debridement of soft tissue involvement has been considered to have a better prognosis.¹⁵ Similarly, intraoperative glycemic control has been well known to control infection leading to an overall decreased morbidity and mortality.¹⁶ One study showed that the adverse outcomes of deranged glycemic control includes more than 50% increase in mortality, a 2.4-fold increase in the incidence of postoperative respiratory infections, two-fold increase in surgical site infections, a threefold increase in postoperative urinary tract infections, doubling in the incidence of myocardial infarction, and an almost twofold increase in acute kidney injury.¹⁷

For patients with deranged glycemic control, insulin was given intraoperatively according to the variablerate intravenous intraoperative infusion (VRIII)¹⁵ and was maintained between 6-10 mmol/L (100-180 mg/dL) with hourly monitoring of blood glucose.¹⁵

This study was a retrospective observational study and the data was collected from patients’ previous records. It was not a comparative study, and we have not observed the long-term outcome of operated patients. These aspects need to be further studied. The sample size was also less. Thus further multicentric studies are required to be conducted in Covid mucormycosis patients to have an elaborate knowledge of such patients as many nondiabetic patients, patients at home isolation who have not received steroids have also suffered from this disease. Further studies will aid in understanding the disease and planning its management.

Nonetheless, this study was an important step in providing data in this pandemic which everyone is experiencing for the first time and gaining new insights every day.

Conclusion

More studies are required to know the exact pathogenesis and its effect on anesthesia. Ultimately, it is the multidisciplinary approach and timely management including postoperative intensive care that helped our patients improve clinically.

Conflict of Interest

None.