key: cord-0782314-nhj2jltv authors: Sirohiya, P.; Vig, S.; Mathur, T.; Meena, J. K.; Panda, S.; Goswami, G.; Gupta, R.; Konkimalla, A.; Kondamudi, D.; Gupta, N.; Ratre, B. K.; Singh, R.; Kumar, B.; Pandit, A.; Sikka, K.; Thakar, A.; Bhatnagar, S. title: Coronavirus disease (COVID-19) associated Mucormycosis: An Anaesthesiologist's Perspective date: 2021-09-12 journal: nan DOI: 10.1101/2021.09.06.21263168 sha: c86787f76a97bb60c002d9647d0d25e9257cabfe doc_id: 782314 cord_uid: nhj2jltv In India, the second wave of coronavirus disease (COVID -19) was associated with a distinct surge in cases of invasive fungal infection with mucormycosis. This disease was seen typically in the sinonasal form in COVID-19 patients. Uncontrolled diabetes, steroid use in COVID-19 treatment, etc. were some of the postulated risk factors for the association of COVID 19 and Mucormycosis. The management plan of these cases included surgical debridement, systemic antifungal therapy, sugar control, and management of antifungal related systemic adverse effects. In this retrospective case record review, we aimed to evaluate the airway management plan, demographics, and overall outcomes in patients undergoing surgical resection for COVID-19 associated mucormycosis. Forty-one (71.9 %) patients had a diagnosis of sino-nasal mucormycosis, fourteen (24.6%) had a diagnosis of rhino-orbital mucormycosis, and 2 patients (3.5%) were diagnosed with palatal mucormycosis. Total 44 (77.19 %) patients had co-morbidities. The most common co-morbidity was Diabetes Mellitus 42 (73.6%), followed by hypertension 21 (36.84%) and Acute kidney injury 14 (28.07%). We used the intubation difficulty scale score to assess intubating conditions. Intubation was easy to slightly difficult in 53 out of 57 patients. In our study, mortality occurred in 7 (12.28 %) patients. The median mortality time was 60 (range, 27-74) days. The median time to hospital discharge was 53.5 (range,10-85) days. Managing COVID-19 on its own is challenging and additional mucormycosis can lead to increased morbidity and mortality. Despite challenges and risks, timely and meticulous interventions can reduce complications. Mucormycosis is an acute-onset, aggressive, and rapidly progressive angioinvasive infection caused by saprophytic fungi of the order Mucorales. The most common underlying risk factor associated with mucormycosis is uncontrolled diabetes mellitus. Hematopoietic stem cell and solid organ transplants, corticosteroid therapy, neutropenia, or drug-induced immunosuppression are other identifiable risk factors. [1, 2] There was a sudden increase in cases of mucormycosis in the second wave of Coronavirus disease in India. [3, 4] The management plan of these cases included surgical debridement, systemic antifungal therapy, sugar control, and management of antifungal related systemic adverse effects. Diabetes mellitus has been identified as the most common coexisting comorbidity. Attention must be given to control blood glucose. [ The mortality rate of mucormycosis associated with COVID-19 is unknown but overall mortality in case of mucormycosis is 54%. [9] There is a risk of involvement of vital structures like the brain and eye, so surgical debridement should be planned on an urgent basis as delay may cause further worsening of prognosis. There may be less time for optimization of patient comorbidities, making perioperative management challenging. As all the patients in our study are positive to COVID-19, the problems encountered due to wearing personal protective equipment, limited staff and supplies are additional difficulties in the management of these patients. [10] To our knowledge, there has been no study reporting on the anaesthetic management of patients with mucormycosis associated with COVID-19 except for few case reports. In this study, we aimed to evaluate the airway management plan, demographics, and overall outcomes in patients undergoing surgical resection for COVID-19 associated mucormycosis. After obtaining approval from the institute ethics committee ( The study included 57 COVID-19 positive patients that underwent surgical resection for mucormycosis under general anaesthesia. Patients with incomplete medical records were excluded from the study. The study was designed as a retrospective case record review that evaluated hospital records of 57 COVID-19 positive patients that underwent surgical resection for mucormycosis in the defined study period. • Primary outcome -to describe the airway management plan in patients with sinonasal mucormycosis posted for surgery • Secondary outcome -to describe the demographics and overall outcomes in patients undergoing surgical debridement of mucormycosis. Routine monitoring including heart rate (HR), noninvasive blood pressure (NIBP), electrocardiogram (ECG), and peripheral oxygen saturation (SpO 2 ) was administered in the operating room for each patient. All the surgeries were performed under general anaesthesia. Following the 3-min preoxygenation with 100% O 2 , anaesthesia was induced with fentanyl (2 µg/kg), intravenous propofol (2 mg/kg), rocuronium (0.9 mg/kg). In 56 patients, orotracheal intubation by using C-MAC video laryngoscope was performed and in 1 patient, nasotracheal intubation was performed using the fibreoptic bronchoscope. All patients were mechanically ventilated using an Avance CS² Anesthesia Delivery System (GE Healthcare) at a frequency of 10-14 breaths per min with a tidal volume of 6-8 mL/kg. Following intubation, the EtCO 2 value was monitored continuously. The tidal volume and the ventilation rate were adjusted to maintain the EtCO 2 value within a range of 35-45 mmHg. Anaesthesia was maintained with sevoflurane or desflurane in a mixture of 50%-50% oxygen and air. A bolus injection of rocuronium was administered as needed. In patients that had no intraoperative complications, neostigmine (0.05 mg/kg) and glycopyrrolate (1/5 dose of neostigmine) were administered to reverse residual neuromuscular blockade at the end of the surgery. Patients who achieved All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this this version posted September 12, 2021. ; https://doi.org/10.1101/2021.09.06.21263168 doi: medRxiv preprint spontaneous respiration, adequate tidal volume (>5 mL/kg), maintaining oxygen saturation >95 % were extubated in the operation theatre and then transferred to the post-anaesthesia care unit (PACU). However, the patients who showed inadequate reversal were transferred to the Intensive care unit (ICU) for elective mechanical ventilation. Duration of anaesthesia was defined as the time between Induction of anaesthesia to transfer of the patient to the post-anaesthesia care unit PACU or ICU. Patient data regarding length of hospital stay and mortality rates were obtained from the hospital records. Length of hospital stay was defined as days between the date of admission in the hospital to the date of discharge/mortality. The study reviewed the demographic, surgical, and clinical records of 57 patients. Patient data regarding drugs, comorbidities, and laboratory parameters were obtained from the hospital records. Postoperative care was conducted in the PACU/ICU. Patients that achieved a Modified Aldrete score of ≥ 9 were transferred to the ward. (11) . Patients who required postoperative mechanical ventilation were transferred to ICU directly from the operation theatre. Postoperative analgesia was provided according to the world health organization's stepladder approach to pain management. [11] Statistical Analysis Data pertaining to selected variables in the study were extracted from the records and entered into MS Excel software version 16.0 (Microsoft Inc.). for summative analysis. The data were summarized using the medians with interquartile ranges [25 th -75 th ] for continuous variables and numbers and =proportions (%) for categorical variables Data were statistically reviewed using IBM SPSS Version 24 (SPSS Inc, Chicago IL, USA). for distribution however it wasn't included in the study for non-comparable groups. , Descriptive data were tabulated into contingency tables and was included in the study results. All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. while the remaining 23 patients had a score of III (40.35 %). [12] Ten (17.54%) patients were active smokers and 10 (17.54%) patients had a history of alcohol intake. Forty-one (71.9 %) patients had a diagnosis of sino-nasal mucormycosis, fourteen (24.6%) had a diagnosis of rhino-orbital mucormycosis (out of which 2 patients were diagnosed with rhino-orbital mucormycosis with cerebral extension), and 2 patients (3.5%) was diagnosed with palatal mucormycosis. Total 44 (77.19 %) patients had co-morbidities. The most common comorbidity was Diabetes Mellitus 42 (73.6%), followed by hypertension 21 (36.84%) and Acute kidney injury 14 (28.07%). Airway assessment, management, and procedural data parameters are presented in Table 2 and patient who had restricted mouth opening (<1 finger), we did nasotracheal intubation using a fibreoptic bronchoscope. First pass intubation success was 92.98 %. The Cormack Lehane grading was 1 in 42.1% and 2 in 49.12 %. [14] Two (3.5 %) patients required intubation stylet for their endotracheal intubation. We calculated the Intubation difficulty score to assess intubating conditions and we found a score of 0 (Easy) in 11 patients, a score of 1 to 4 (slightly difficulty) in 42 patients, and a score >5 (moderate to major difficulty) in 3 patients. [15] The median percentage of glottic opening (POGO) score was 80 (range 20-100) % and median intubation time was 15 (range, 10-180) seconds. Surgical debridement of mucormycosis is an aggressive procedure and perioperative anesthetic management of the patients is challenging. Involvement of the oropharyngeal region by fungus and supraglottic edema may cause mask ventilation and endotracheal intubation. [16] In our study, mask ventilation was not difficult in any of our patients. First pass intubation success was 92.98 %. Two attempts were taken in 4 (7.01 %) patients. Two patients had required intubation stylet for their endotracheal intubation and two patients had difficulty in guiding endotracheal tube through glottis in the first attempt but the second attempt was successful. In one patient, restricted mouth opening was present, so, fibreoptic intubation was performed. Rest all patients are intubated by C-MAC video laryngoscope as per departmental COVID-19 protocol. The intubation difficulty score was calculated with the help of the Intubation difficulty scale. Eleven patients had no intubation difficulty, 42 patients had slight intubation difficulty (score 1-4), 3 patients had moderate to major intubation difficulty (score >5). We had a dedicated COVID-19 operation theatre with all the healthcare staff wearing level 3 personal protective equipment. [17] As an anaesthesia, we checked all equipment and drugs for anticipated or unanticipated difficult airway management. We had different sized masks, stylets, bougies, laryngeal mask airways of different sizes, video laryngoscope (C-MAC) with blades of different sizes, fibreoptic-guided intubation kit, 2 working suction apparatus, and emergency tracheostomy trolley for management of the unexpected difficult airway. All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this this version posted September 12, 2021. ; https://doi.org/10.1101/2021.09.06.21263168 doi: medRxiv preprint COVID-19 itself is a major contributor to morbidity and mortality due to dyspnoea, poor functional status, chest pain or tightness, hypercoagulability, endocrine abnormalities particularly impaired glycaemic control, etc. This, in addition to mucormycosis, leads to even worsening of prognosis in these patients. [18] In our study 42 (73.68 %) patients had a history of diabetes which was managed by administration of insulin perioperatively. Central venous catheters may be required peri-operatively for blood or blood product transfusion, fluid replacement, inotropic or vasopressor support, and for infusion of amphotericin B for a prolonged period. [19] We used Groshong® PICC catheter (4 and 5 Fr) in 7 patients and internal jugular venous cannulation in 47 patients. The use of systemic amphotericin B in the management of COVID-19 associated mucormycosis has its distinct toxicities, most importantly nephrotoxicity. There are other side effects of amphotericin B such as hypokalaemia, hypomagnesemia, fever, dyspnoea, shivering, and hypotension. [20] In our study, 14 patients had pre-operative amphotericin Binduced nephrotoxicity. The primary aim of surgical management is to debride all necrotic tissues. Our patients received both antifungal treatment and surgical debridement. The overall mortality of mucormycosis is 54%. [9] The mortality rate of mucormycosis associated with COVID-19 is still unknown. In our study, mortality occurred in 7 (12.28 %) patients. The Our study has some limitations. First, the study had a retrospective nature and was based on the analysis of anaesthesia and hospital records. Second, all the patients were from a single center. Our study has one strength as this is the first of its kind study in anesthetic perspectives of COVID-19 associated mucormycosis that can be used as a platform for further studies on this topic. All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this this version posted September 12, 2021. ; * items are mutually non-exclusive preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this this version posted September 12, 2021. ; A multicentre observational study on the epidemiology, risk factors, management and outcomes of mucormycosis in India Global Epidemiology of Mucormycosis 000 cases of rare infection Clinical Features, Demography and Predictors of Outcomes of SARS-CoV-2 Infection in a Tertiary Care Hospital in India-A Cohort Study Epidemiology and Diagnosis of Mucormycosis: An Update Anesthetic management of rhinoorbitocerebral mucormycosis; Focus on challenges Amphotericin B: side effects and toxicity Second wave of COVID-19 pandemic and the surge of mucormycosis: Lessons learnt and future preparedness: Indian Society of Anaesthesiologists (ISA National) Advisory and Position Statement Mucormycosis Statistics | Mucormycosis | Fungal Diseases | CDC. 2020 Barriers to using personal protective equipment by healthcare staff during the COVID-19 outbreak in China Prediction of difficult laryngoscopy: Extended mallampati score versus the MMT, ULBT and RHTMD Videolaryngoscopy and Cormack and Lehane grading The Intubation Difficulty Scale (IDS) Mucormycosis Supraglottitis on Induction of Anesthesia in an Immunocompromised Host 2019-02-11-aide-memoire-for-levels-of-personal-protective-equipment-ppe-forhealthcare-workers-for-patientcare Rhino-Orbital Mucormycosis Associated With COVID-19 Vascular access in COVID-19 patients: Smart decisions for maximal safety Anesthetic considerations in the management of mucormycosis PT (sec) The anesthetic management of mucormycosis associated with COVID-19 is challenging because of its perioperative effects. Managing COVID-19 on its own is difficult and additional mucormycosis can lead to increased morbidity and mortality. Despite challenges and risks, timely and meticulous interventions can reduce complications.