Anaesthetic management of a patient with eosinophilic granulomatosis with polyangiitis for internal fixation of a fractured femur

Abstract

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease with an estimated annual incidence of 0.5–6.8 per million. It is characterised by necrotising vasculitis with multiorgan eosinophilic infiltration. Pulmonary manifestations are the most common presentation of EGPA, and cardiac complications are the most common cause of death. Anaesthetic management of EGPA is challenging due to perioperative pulmonary complications, multiorgan involvement and greater risk of cholinesterase enzyme deficiency. We are reporting the anaesthetic management of a 58-year-old woman, diagnosed with EGPA 3 years ago, who underwent urgent intramedullary nail insertion for a femur fracture. The anaesthetic technique comprised femoral nerve block and spinal anaesthesia, thereby avoiding (1) the need for upper airway manipulation, (2) potential adverse effects of anticholinesterase drugs (for reversal of neuromuscular blockade) and (3) histamine release associated with morphine administration perioperatively. Surgery and anaesthesia were uneventful.

BACKGROUND

Eosinophilic granulomatosis with polyangiitis (EGPA) formerly named Churg-Strauss syndrome (CSS) is a rare disease with an estimated annual incidence of 0.5–6.8 per million.^{1 2} It is characterized by small vessel necrotizing vasculitis, multiorgan eosinophilic infiltration and intravascular or extravascular granuloma formation.³ The aetiology of EGPA remains unclear.⁴

Pulmonary manifestations in the form of asthma with patchy infiltrates are the most common presentation.⁵ Other clinical manifestations include cardiac symptoms, cutaneous lesions (palpable purpura), gastrointestinal symptoms (diarrhoea, abdominal pain) and renal involvement (focal segmental glomerulonephritis). Given the non-specific nature of its clinical presentation, a definitive diagnosis can be delayed until the later stages of the disease, which might contribute to a greater mortality rate.⁶

Anaesthetic management of EGPA is challenging due to airways hyperactivity, the fact that several systems are affected⁵ and decreased activity of plasma cholinesterase.⁷ We are presenting the anaesthetic management of a patient with EGPA who underwent intramedullary nail insertion for a fractured femur.

CASE PRESENTATION

A 58-year old woman presented for emergency intramedullary femoral nail insertion following subtrochanteric femur fracture after her leg gave away while walking. She was known to have EGPA and suffered from asthma, recurrent lower respiratory tract infections and sinusitis over the preceding 5 years. She was diagnosed with EGPA 3 years prior to this presentation. According to the five-factor scoring system which is used to predict the survival of EGPA patients, our patient would have scored 0 with a 5-year mortality rate of 9%. Her surgical history included mastectomy for breast cancer and thyroidectomy. She used to take salbutamol inhaler 100 μg three times per day, long-term anticholinergic inhaler 2.5 mg two times per day, formoterol fumarate/fluticasone propionate inhaler (long-acting beta2 agonist with corticosteroid) 10 μg two times per day and oral corticosteroids (prednisolone 5 mg/day) to control her chest symptoms. An urgent intramedullary femoral nail surgery was planned for her subtrochanteric femur fracture.

INVESTIGATIONS

Preoperative laboratory tests demonstrated normal coagulation and did not show hyper-eosinophilia. Renal and liver function tests were within the normal range. The autoimmune assay revealed positive antineutrophil cytoplasmic antibodies (ANCAs).Given her age (58 years) and the relatively innocuous mechanism of injury, specimens obtained by reaming the intramedullary canal and femoral head were collected during surgery to rule out malignancy. Microscopic examination of those specimens revealed no malignant cells

TREATMENT

After placement of a wide bore intravenous drip and an arterial line under local anaesthetic infiltration, 3mg of midazolam intravenous was administered. With standard monitors in place, hydrocortisone 25 mg was administered intravenously in the procedure room in addition to her usual morning usual steroids dose. After obtaining verbal consent, a femoral nerve block was performed with ultrasound guidance using 10 mL of bupivacaine 0.25% and 10 mL of lignocaine 2%. A single-shot spinal anaesthetic at level L3–L4 was performed with a 25-G Whitacre pencil-point needle and 12.5 mg of bupivacaine 0.5% was administered. The level of spinal anaesthesia block was found to be higher than anticipated (absence of sensation to cold spray up to T6 level). Her blood pressure decreased to 70/40 mm Hg 20 min after spinal anaesthesia. A phenylephrine infusion was started at 30 μg/min and adjusted to maintain her blood pressure at preoperative levels for the remainder of surgery (which lasted for 84 min). She was transferred to recovery where the phenylephrine infusion was weaned gradually, and then she was transferred to the ward after 2 hours.

OUTCOME AND FOLLOW-UP

The patient stayed in the ward for three days, which was clinically uneventful and then transferred to a stepdown unit to complete physiotherapy and rehabilitation. On follow-up 3 months later, her fracture was healing well and her chest condition was stable.

DISCUSSION

EGPA, formerly named CSS/allergic granulomatosis and angiitis was initially described in 1950 by Churg and Strauss based on autopsies of 13 patients who shared a clinical picture of severe asthma, fever and hypereosinophilia.³ EGPA is a rare disease with an incidence in Europe ranging from 10.7 to 14 per million.⁸ The mean age of diagnosis is 40 years; our patient was diagnosed at the age of 55 years.⁹ In children, it is less common and usually has a very aggressive course with more prominent respiratory and cardiovascular clinical features.^{10 11} There is no difference in the incidence of EGPA between male and female individuals.¹²

The aetiology of EGPA is unknown. It has been linked to abnormal immune function because ANCAs are detected in 40%–60% of patients and of the prevalence of allergic manifestations (allergic rhinitis, asthma and positive skin tests). Our case demonstrated a positive ANCA test and allergic manifestations over 5 years. It has also been suggested that genetic factors may play a role in the development of EGPA.^{13 14}

Severe asthma, nasal and sinus symptoms and peripheral nerve involvement are the most common presentations of EGPA.^15–17 In this case, our patient suffered from asthma, nasal and sinus problems, and neuropathic manifestations in the form of numbness, pins and needles along her leg and foot.

Other clinical features of EGPA include fever, myalgia, arthralgia, skin rash, weight loss, abdominal pain, diarrhoea and renal involvement.¹⁶ Clinical manifestations of EGPA typically develop in three phases that may overlap.¹⁸ These are (1) a prodromal or allergic phase that often occurs in patients in their 20s or 30s and is associated with late-onset asthma, worsening asthma in those already affected and allergic rhinitis.¹⁹ However, more severe symptoms such as nasal sinusitis and nasal polyps can occur.¹⁸ (2) An eosinophilic phase is due to eosinophilic infiltration of organs and tissues, particularly the lungs, heart and gastrointestinal tract (GIT).¹⁹ (3) A vasculitic phase is characterised by inflammation of small and medium-sized blood vessels and reduction of blood flow to tissues and organs. This phase is characterised by blood clots, infarction, ulceration of the GIT, perforation of the bowel and cardiac involvement.²⁰ Cardiac manifestations include symptoms similar to those of acute coronary syndrome, myocarditis and pericardial effusion and are responsible for approximately half of EPGA-related deaths.²¹

In 1990, The American College of Rheumatology listed six criteria for diagnosis²²; the patient must have four of these to be considered CSS positive. These are as follow:

1. Asthma

2. Hypereosinophilia greater than 1500/μL or greater than 10% of white blood cell (WBC) volume.

3. Mono or polyneuropathy.

4. Patchy infiltrate in chest X-ray.

5. Sinus problems, history of acute or chronic sinusitis.

6. WBCs present outside blood vessels.

Our patient was diagnosed based on her clinical manifestations (asthma, sinus problems, neuropathy) and patchy infiltrates on her chest X-ray. However, on admission she had a normal eosinophil count of 0.37×10⁹/L.

Because pulmonary manifestations are the most common features of EGPA, pulmonary function tests are indicated before any surgery especially if general anaesthesia is planned to predict perioperative pulmonary complications. Our patient’s asthma was well controlled (with inhalers and oral steroids), and her last attack was more than 6 months ago. Our centre protocol requires that patients with femoral fracture undergo definitive fixation within 24–48 hours from admission when possible. This is based on the assumption that delay will increase the risk of complications and the duration of hospital stay and is consistent with the National Institute for Health and Care Excellence guidelines 2011 ‘Hip fracture management’.²³

The patient we describe was admitted to the hospital over the weekend when pulmonary function testing is generally not available. In view of this, the urgent nature of femur fixation surgery and the planned regional anaesthesia technique, we elected to proceed without pulmonary function tests.

Cholinesterase enzyme deficiency has been reported previously in two patients with EGPA (CSS).⁷ Hence, suxamethonium should be avoided and non-depolarising muscle relaxants with minimal histamine release (rocuronium, vecuronium) can be used. However, anticholinesterase drugs should be used cautiously as they can provoke bronchoconstriction and increase bronchial secretions.

Systemic glucocorticoids are the mainstay in the management of EGPA at a dose of 0.5–1 mg/kg/day.²⁴ Most of the patients without multiorgan involvement will achieve remission on glucocorticoids alone and these can be tapered gradually after remission has been attained over a period of 12–18 months.²⁵ However, immunosuppressive therapy (cyclophosphamide) is usually required in patients with multiorgan involvement (cardiac, renal, gastrointestinal and central nervous system) or refractory manifestations.^26–28

The prognosis of EGPA has traditionally been scored using a five-factor score that was designed in 1996 and revisited in 2011.^{29 30} The negative prognostic elements are age >65 years, cardiac symptoms, gastrointestinal involvement and renal insufficiency (defined as creatinine concentration ≥150 μmol/L). The presence of ear nose and throat symptoms is a positive prognostic feature.³⁰

The prognosis of patients with EGPA has been greatly improved since the introduction of systemic glucocorticoids and immunosuppressive therapy. Five-year survival rate for patients managed in this way has been reported to be 70%–90% (in comparison with 50% deaths within 3 months of untreated patients).^{31 32}

Im et al reported a case of CSS who underwent endoscopic sinus surgery under general anaesthesia during which muscle relaxants were avoided and tracheal intubation was managed with the aid of propofol, remifentanil infusion and inhaled sevoflurane. However, haemodynamic compromise was reported during tracheal intubation and was managed by ephedrine boluses.³³ Chia reported a case of CSS who underwent hysterectomy under general anaesthesia, tracheal intubation was facilitated by rocuronium 50 mg and reversed using sugammadex 200 mg to avoid the problems associated with anticholinesterase administration.³⁴

We planned our anaesthetic technique to avoid general anaesthesia and tracheal intubation to minimise the risks associated with hyperactive airways, muscle relaxant and anticholinesterase administration and the potential for histamine release such as can occur with morphine administration.

EGPA presents challenges to an anaesthetist, particularly when a patient requires urgent major surgery. We describe a case in which a combination of regional anaesthetic techniques appeared to mitigate the perioperative risks for a patient undergoing intramedullary nail insertion for a fractured femur.

Patient’s perspective.

When I first found out I have Churg Strauss, I felt relief from one hand—as I was constantly sick with my chest and all the tests were coming back clear and no one knew what was wrong with me and eventually the doctors found the problem—but I was also worried, because it is a very rare disease and only little is known about it.

I am aware of all the medication I am on to keep me going but also have a negative impact on my body when I broke my bone my first thoughts were that I will not be able to walk for a long time, but I started to be mobile faster than expected.

The operation itself was long and a bit uncomfortable as I was fully aware and could hear absolutely everything doctors were doing. Beside that overall experience and care were very good.

Learning points.

• Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease with unclear aetiology.

• Pulmonary manifestations are the most common presentation of EGPA.

• Systemic glucocorticoids are the cornerstone of EGPA management.

• Anaesthetic management of EGPA can be challenging particularly when the patient requires urgent and major surgery.

• Regional anaesthetic techniques, when used in combination, may mitigate perioperative risks associated with general anaesthesia and with muscle relaxant, anticholinesterases and morphine administration.