INTRODUCTION
Mucormycosis is an aggressive, fulminant, invasive fungal infection that can occur in immunocompromised patients with diverse precipitating factors. Several cases of mucormycosis following coronavirus disease 2019 (COVID-19) infection have been reported worldwide, particularly from India.[1] The diabetic COVID-19 patient receiving corticosteroids or other immunosuppressants is exceptionally vulnerable to the development of mucormycosis.[2] Treatment options for post-COVID mucormycosis include antifungal agents like amphotericin B, surgical debridement, reversal of underlying predisposing factors, and adjuvant therapy.[3] There are very few studies that address anaesthetic management in the background of compromised airway and systemic complications associated with post-COVID mucormycosis affecting the rhino-orbito-cerebral region.[4,5] Hence, this study was planned to evaluate the anaesthetic challenges, relationship of mucormycosis with comorbidities, steroid treatment, intubation difficulties, post-anaesthesia recovery status, and perioperative complications in terms of morbidity and mortality among patients undergoing surgical resection of post-COVID ROCM.
METHODS
In this case series, records of all adult patients (≥18 years of age) with American Society of Anesthesiologists Physical Status (ASA-PS) I to IV, of either sex, with previous history of COVID-19 (confirmed with reverse transcription polymerase chain reaction [RT-PCR]), and having confirmed diagnosis of ROCM on biopsy, who underwent surgical interventions under general anaesthesia between the first week of May and the second week of June 2021 were collected retrospectively. Post-COVID mucormycosis patients with a negative RT-PCR report and with frontal headache, blurring of vision, numbness of the cheek, facial swelling, features suggestive of cranial nerve involvement, nasal or sinus congestion, black lesion on nasal bridge or upper inside of mouth (palatal region), and who underwent operative intervention were included in this case series. On the other hand, patients found to be RT-PCR positive for COVID-19, those managed medically, and those with incomplete medical records due to transfer to other hospitals were excluded. Data were collected from the medical record section after obtaining approval from the institutional ethics committee. A total of 49 mucormycosis patients were admitted to the hospital during the study period. Surgical intervention was carried out on 33 patients. Finally, the data of 30 patients were collected and analysed [Flow Diagram 1].
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Flow Diagram 1: Enrollment of cases
Demographic parameters of the patients were recorded; patients were assessed for any comorbidities, and investigation results were collected. Preoperatively, the airway of each patient was assessed by mouth-opening, Mallampati grading, and neck movement. Most of the patients were induced by propofol or etomidate, and dexmedetomidine was used as sedative before fibreoptic bronchoscopy and surgical tracheostomy.
Difficult intubation was graded according to the Modified Intubation Difficulty Scale (MIDS). Oxygen, nitrous oxide, isoflurane/sevoflurane, and atracurium besylate/vecuronium were used for maintenance of anaesthesia. During the intraoperative period, the lung protective ventilation strategy was applied, aiming at a plateau pressure of 25–30 cm of water. Intraoperative vitals, urine output, arterial blood gas monitoring were done. Episodes of hypotension and arrhythmia were recorded and treated appropriately during the intraoperative period. Reversal of residual neuromuscular block was achieved using neostigmine and glycopyrrolate. Majority of the patients received insulin infusion. Isotonic intravenous fluid was used for peri-operative maintenance whereas, colloids, inotropes, vasopressors were administered in patients with shock refractory to crystalloid. Potassium supplementation was given as needed. After operation, all patients were shifted to the critical care unit (CCU) with all monitors and high-flow oxygen therapy. Postoperative follow-up and management of complications (if any) of each patient were done till live discharge from the hospital or death.
Data were recorded in a Microsoft Excel spreadsheet for final analysis and interpretation. IBM SPSS Statistics version 22 was used for the analysis.
RESULT
This case series on post-COVID mucormycosis revealed that most of the patients were male (63.3%) and obese (66.7%) and had diabetes mellitus as the most common comorbidity (96.7%). Other comorbidities were hypertension, hypothyroidism, chronic obstructive pulmonary disease (COPD), chronic kidney disease, cerebrovascular accident, and ischemic heart disease. Urine for ketone body was positive in 20% of patients. All patients received a corticosteroid. Preoperative airway assessment revealed that 33.3% of patients had Mallampatti grade III and 23.3% had grade IV; 60% had adequate mouth-opening (inter-incisor gap was equal to the width of patient’s own three fingers [index, middle, and ring fingers]). Sixty percent of patients had difficult airway management, among them six patients (20%) with MIDS score 3–5 required video laryngoscope for intubation; nine (30%) required fibreoptic bronchoscope for intubation; and three (10%) could not be intubated, for whom surgical tracheostomy was done [Table 1]. Forty percent of patients had abnormal electrocardiography (ECG) findings, and 30.0% had abnormal echocardiography reports, such as left ventricular systolic dysfunction, regional or generalised left ventricular wall motion abnormality, right ventricular dysfunction, dilatation of left atrium, and/or left ventricle. They were induced with etomidate, and sedation was done using dexmedetomidine before fibreoptic bronchoscopy or tracheostomy [Table 1].
Table 1: Association of mouth-opening and technique of intubation with Modified Intubation Difficulty Scale (MIDS) score
Preoperative investigation revealed neutrophilic lymphocytopenia along with increased creatinine (1.3687 ± 0.5309 mg/dl), decreased serum potassium (3.23 ± 0.659 mmol/L), decreased albumin (2.7 ± 0.4745 g/dl), increased residual inflammatory marker interleukin-6 (IL-6; 27.03 ± 24.90 unit/L), C-reactive protein (69.37 ± 53.28 mg/L), lactate dehydrogenase (548.86 ± 287.62 unit/L), and ferritin (416.08 ± 193.39 ng/ml). Glycosylated haemoglobin was (8.4733 ± 4.5213) %, fasting blood sugar was 225.33 ± 114.96 mg/dl, and post prandial blood sugar was 316.46 ± 157.23 mg/dl. Average duration of anaesthesia was 119.07 ± 39.45 minutes. Two patients (6.7%) had delayed recovery from general anaesthesia and required postoperative ventilatory support.
Eight deaths were recorded in this study and were all due to medical complications like septic shock, disseminated intravascular coagulation, dyselectrolytemia, renal impairment, and arrhythmia.
Patients who died had a higher mean age (62.12 ± 14.12 years) compared to those with live discharge (48.5 ± 10.19 years) (P = 0.0068). Presence of ketone bodies in urine had a strong association with final outcome (P = 0.013).
Association of preoperative American society of anesthesiologists-physical status (ASA-PS) status and final outcome was highly statistically significant (P = 0.0019). ASA-PS grading of upper airway was less in live patients. Mean CCU stay was also less in patients who were discharged live from the hospital [Table 2].
Table 2: Association between final outcome of patients with ASA-PS and duration of stay in critical care unit
Twenty patients (66.6%) had postoperative complications such as cardiac arrhythmia, dyselectrolytemia, haemorrhage, hypoglycaemia and septic shock. The association between postoperative complications and final outcome was statistically significant (P = 0.0357).
DISCUSSION
The most convincing risk factors for mucormycosis appear to be unrecognised, uncontrolled diabetes compounded by the indiscriminate use of steroids at high doses and poor hygiene even in a non-hypoxic patient.[2] Twenty patients (66.7%) had poor oral hygiene and twelve (40%) were addicted to gutkha in this series. Dental pain was a common presentation (53.3%). Diabetes mellitus was the most common comorbidity (96.6%) with high HbA1c, fasting blood sugar, and post prandial blood sugar levels, and all patients had prior treatment with some form of corticosteroid. These data indicate a close association between post-COVID mucormycosis and uncontrolled diabetes. In one multicentric study, uncontrolled diabetes was present in 66.2% of cases of COVID-associated mucormycosis (CAM), among whom 78.7% received glucocorticoid treatment for COVID-19 management. Inappropriate glucocorticoid was independently associated with late CAM.[6] Lymphocytopenia with prolonged depletion of T cell subset is an important feature of COVID-19 and is also a known risk factor for opportunistic infections including invasive mucormycosis.[7] Hyperglycaemia due to affection of the beta cells of the pancreas by SARS-CoV-2 may be another contributing factor.[7] Patients with ROCM should be considered as cases of anticipated difficult mask ventilation and endotracheal intubation because of associated epiglottitis, sub- and supra-glottic oedema, compromised mouth-opening due to jaw erosion and pain, bleeding palatal ulcers, palatal perforations, crusts in the nose, oroantral fistulas, and diabetes mellitus–induced joint stiffness. Facial swelling, proptosis, and perioral wounds due to the use of tight-fitting and non-invasive ventilation masks during COVID treatment can hinder mask ventilation.[3,8] In the present series, 20% of patients required video laryngoscope-assisted intubation, 30% required fibreoptic bronchoscopy, and 10% required surgical tracheostomy.
Records of patients indicate that requirement of inducing agents, analgesics, and muscle relaxants were less in this series. Low serum albumin, hypovolemia, or altered volume of distribution may be the possible explanation. Succinylcholine was not used in patients who recovered from prolonged critical COVID-19 illness, to prevent myopathy induced hyperkalaemia.[9]
In our series, eight patients (26.7%) succumbed to their illness. Karaaslan et al.[3] also reported a 25% mortality rate in their series.
In this case series, elevated serum IL-6, C-reactive protein, D-dimer, ferritin, and lactate dehydrogenase (LDH) were found in ROCM patients who succumbed to their illness. Skiada et al., in their study, showed that increased inflammatory markers were poor prognostic markers for postoperative mucormycosis patients. Residual cytokine storm with elevated IL-6, C-reactive protein, D-dimer, ferritin, and LDH are the potential contributors to mortality.[10]
In the present study, two patients had acute kidney injury, of whom one patient succumbed. Pre-renal factors with volume depletion due to fever and poor oral intake, hyperinflammatory syndrome leading to cytokine-mediated renal tubular injury, and use of amphotericin B—a proven nephrotoxic drug—might be potentially precipitating factors of acute kidney injury in these patients.
In our series, 6.7% of patients had delayed recovery from general anaesthesia, requiring postoperative ventilatory support. Desai et al.,[4] in their study, found that 9.3% of patients experienced delayed recovery. Electrolyte disturbances such as hypokalaemia and hypomagnesemia resulting from use of amphotericin B may interfere with neuromuscular blocking drugs, thereby culminating into delayed recovery.
CONCLUSION
Meticulous preoperative evaluation and optimisation followed by a carefully planned anaesthesia administration coupled with strict hemodynamic monitoring, perioperative glucose control, preparation with difficult airway cart, maintenance of metabolic and electrolyte balance, and postoperative CCU management are of paramount importance for better outcome in COVID-recovered patients scheduled for resection of ROCM.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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