European Journal of Cardiovascular Medicine

Mucormycosis is a rare, aggressive fungal infection, typically affecting immunocompromised individuals, particularly those with diabetes mellitus. Rhino-orbital-cerebral mucormycosis, a severe subtype, poses significant anaesthetic challenges due to its rapid progression and systemic involvement. This report discusses a case complicated further by Raynaud’s phenomenon secondary to ovarian cancer management and cavernous sinus thrombosis, and outlines key perioperative management strategies.

A 56-year-old female (P3L3A1), known hypertensive on Tab Telmisartan 40mg and Hydrochlorothiazide 12.5 mg OD for 12 years and diabetic for 3 years managed on oral hypoglycemic agents Tablet metformin 500mg and sub cutaneous insulin (HbA1c -6.6). Patient developed shortness of breath around one year back and abdominal distension which was increasing in severity over 10days.CT abdomen showed International Federation of Gynaecology and Obstetrics (FIGO) stage 3C adenocarcinoma of the left ovary for which she received four cycles of paclitaxel and carboplatin chemotherapy over a span of 2months, at the end of which she developed neutropenia and rhino-orbital mucormycosis. Within a week of chemotherapy patient developed severe pain and burning sensation in bilateral soles with nailbed tenderness followed by gangrenous toes (? Raynaud’s phenomenon) (Fig 1). She underwent 3 sessions of orbital wound debridement and was treated with liposomal Amphotericin B, posaconazole, Apixaban 5 mg BD, and Aspirin 75 mg OD.

Preoperative MRI brain showed bilateral cavernous sinus thrombosis and a peripheral collection compressing the left optic nerve, with no evidence of increased ICP. CT abdomen revealed infrarenal aortic plaques with 50% diffuse sclerosis. (Figure 2) Bilateral lower limb arterial doppler showed biphasic waveform in anterior, posterior tibial and dorsalis pedis arteries. In the preoperative period she received insulin, erythropoietin, multiple blood transfusions, and electrolyte correction.

Patient of orbital mucormycosis with palatal necrosis and digital gangrene

CT abdomen showing infra-renal aortic plaques and MRI brain with CST

Vascular surgeon’s opinion was to stop apixaban for 48 hours before procedure and to restart 48 hours after surgery and use intermittent compression stockings in the perioperative period (caprini score 8).

Pre anaesthetic evaluation revealed anaemia (Hb:9.6g/dL), normal coagulation profile, corrected electrolyte levels, normal Thyroid Function Tests, Liver Function Tests, Chest X Ray. Reduced mouth opening (two finger breadths) was noted due to left eye cellulitis, normal fundoscopy and echocardiogram. She was posted for staging laparotomy with left orbital sequestrectomy. Apixaban was stopped 48 hours prior.

On the day of surgery ASA-recommended monitoring of Electrocardiogram, pulse oximetry, non-invasive blood pressure was connected. 18 G IV cannula was secured on dorsum of right-hand and anaesthesia was induced after preoxygenation and mask ventilation aided by gauze placed over the orbital defect, with propofol 120 mg, fentanyl 100 mcg, and rocuronium 60 mg. Intubation was done with a size 7 COETT using direct laryngoscopy, which displayed Cormack Lehane of grade 1. Maintenance of anaesthesia included isoflurane (for fungistatic properties), air, oxygen, intravenous (IV) morphine 4mg, and warm IV fluids (Ringer Lactate 1500ml). Attention was paid to maintaining core temperature at around 37⁰C using warm IV crystalloids (Hotline) and Bair hugger. Hourly glucose monitoring(150-160mg/dl) and temperature regulation were performed throughout the two hour duration of surgery.

Subcutaneous wound infiltration of 0.25% bupivacaine 10 ml and ultrasound guided Bilateral Transverse Abdominis Plane block (15 ml 0.2% ropivacaine) was administered at the end of surgery. Patient was reversed with sugammadex 100mg, extubated after adequate reversal of neuromuscular blockade (Train of Four >0.9). Postoperatively fentanyl transdermal patch of 25ug/hr was placed on left shoulder and intravenous paracetamol were used as postoperative analgesics. She was discharged on postoperative day three following an uneventful hospital course.

Mucormycosis is a fungal infection caused by filamentous Zygomycetes which predominantly invade blood vessels and mucocerebral mucormycosis has a high mortality of 40-90%. The key to successful control of mucormycosis is early and aggressive surgical resection combined with early, high-dose systemic antifungal therapy

Fungi invade blood vessels causing vasculitis, thrombosis, and necrosis, and via pro-thrombotic states can lead to cavernous sinus thrombosis (CST) and peripheral ischemia. Also, systemic infection produces inflammatory cytokines, endotoxins, and the vascular damage can trigger peripheral vasospasm or secondary Raynaud-like symptoms. So, in a patient with mucormycosis and CST, Raynaud's may appear as part of:  systemic vasculitis, thrombotic picture, or Sepsis-related peripheral ischemia.

Raynaud’s phenomenon (RP) is an exaggerated vasospastic response to cold or emotional stress that can be either primary (idiopathic) or secondary to several underlying conditions such as connective tissue disorders, vascular obstructions, or drugs. This patient developed secondary RP to maybe paraneoplastic association to ovarian cancer, paclitaxel or even mucormycosis itself. ^(1-3) The exact cause of RP caused by cancer treatments is not well understood and likely involves multiple factors. One of the reasons is damage to the blood vessels caused by chemotherapeutic drugs, leading to endothelium dysfunction that remains even after treatment. Patients with RP syndrome after chemotherapy have been found to have an enhanced central sympathetic vasoconstrictor reflex and altered autoregulation. ^(4-8)

Raynaud’s phenomenon increased the complexity of the procedure, requiring avoidance of vasoconstrictive agents and maintenance of normothermia. ⁽⁹⁾ Invasive monitoring of blood pressure of radial artery was avoided as previous studies mentioned higher incidence of finger necrosis. ⁽¹⁰⁾ Femoral artery access was also examined and deferred due to ongoing sepsis, proximity to the surgical site and infra renal aortic plaques causing 50% diffuse stenosis, and due to the gangrene of toes.

Toe gangrene was initially suspected to be due to peripheral vascular disease. However, all peripheral pulses were palpable and there was good response to medical therapy and chemotherapy was continued, favouring a vasospastic rather than occlusive cause. Doppler showed normal proximal waveforms with distal biphasic flow, indicating small-vessel involvement. With high CRP (180mg/L) reflecting infection/inflammation, mildly raised ESR (32mm/hr), and negative rheumatoid factor, autoimmune vasculitis was unlikely. Overall, the picture was consistent with secondary Raynaud’s phenomenon (paraneoplastic / chemotherapy-related) with superimposed distal thrombotic compromise, rather than classic atherosclerotic PVD.

Cavernous sinus thrombosis is a rare life-threatening condition secondary to septic condition which could be the mucormycosis in this patient. Several case reports of the same have been reported. ^(11-13) Raised intracranial tension is seen in about 10% of patients with CST, and was one of the reasons to avoid neuraxial blockade.

The pros and cons of continuous epidural techniques were considered and deferred considering the progressive cavernous sinus thrombosis (raised intracranial tension risk), due to hypotension risks associated with extensive atherosclerosis, and potential need for early anticoagulation in view of deep vein thrombosis risk.

This case underscores the multifactorial considerations in the anesthetic management of patients with mucormycosis, diabetes, Raynaud’s phenomenon, cavernous sinus thrombosis and recent chemotherapy. Close monitoring, interdisciplinary planning, and individualized anesthetic strategies are crucial for optimizing outcomes.

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