Anesthetic considerations in pemphigus vulgaris: Case series and review of literature.

A case series of the anesthetic management of 4 patients with pemphigus vulgaris (PV) undergoing emergency/elective surgery is presented. PV presents serious concerns for anesthesiologist, when present, in a surgical patient but handling of these patients with care and taking all the due precautions can decrease morbidity and airway-related complications. Various clinical presentations and precautions, which should be ensured during anesthesia in patients suffering from PV, are discussed.

INTRODUCTION

In patients suffering from severe pemphigus vulgaris (PV), an autoimmune cutaneous blistering disorder, important precautions during the anesthesia prevent morbidity. Anesthesiologists do not encounter bullous skin lesions frequently, but when present may impose serious concerns in the management of a surgical patient. The presence of oropharyngeal and laryngeal lesions produce difficulties in airway management. Precautions are necessary to avoid trauma to skin and mucous membranes while performing the procedures as sliding pressure results in separation of even the normal-looking epidermis from the dermis (Nikolsky sign) in these patients. As pemphigus is usually treated by high-dose steroids, suppression of adrenal gland is another hazard to be dealt by the anesthesiologist in the perioperative period. In this case series we highlight the anesthetic management of 4 patients with PV undergoing elective or emergency surgery.

CASE REPORT

Case 1

A 32-year-old hemodynamically stable, female patient, with PV was admitted in the emergency with abdominal pain since 2 days prior to admission. Her chest X-ray showed air under the diaphragm. She was on oral prednisolone 20 mg/day for encrusted and infected vesicles and bullae over the face, tongue and buccal mucosa, front of the chest, abdomen, both arms and legs. Her ECG, hemoglobin, coagulation profile and kidney function tests were normal. An emergency exploratory laparotomy was planned.

Monitoring in the form of heart rate (HR), electrocardiogram (ECG), arterial oxygen saturation (SpO2) and noninvasive blood pressure (NIBP) was initiated. A peripheral intravenous access was achieved in a lesion-free area.

She was premedicated with intravenous (iv) ranitidine 50 mg, glycopyrrolate 0.2 mg, and fentanyl 70 μg. Anesthesia was induced with intravenous propofol 90 mg; and 25 mg of hydrocortisone was given at induction. After ensuring bag mask ventilation 100 mg of injection succinylcholine was given iv and direct laryngoscopy was performed. The oral cavity was full of encrusted lesions. After gentle suctioning, endotracheal intubation was done with a well-lubricated 7.5 mm tracheal tube (TT) under direct vision. After inflating the cuff, throat was packed with saline-soaked gauzes to stop the bleeding. Anesthesia was maintained on 66% N2O and 34% O2 along with titrated propofol infusion. Neuromuscular blockade (NMB) was achieved with injection vecuronium bromide. Exploratory laparotomy revealed an ileal perforation, which was sealed and end ileostomy done. During one and a half hour of surgery, the patient remained hemodynamically stable. At the end of the surgery, throat pack was removed after gentle suction of the oral cavity. NMB was reversed with injection neostigmine 2.5 mg and injection glycopyrrolate 0.4 mg iv. After an adequate reversal of NMB, the patient was extubated. The postoperative course was devoid of any respiratory issues. She was put on injection hydrocortisone 100 mg/day, which was tapered off gradually over the next 4 days.

Case 2

A 35-year-old febrile male patient came to the emergency room with gradually increasing pain and swelling in the right gluteal region over 1 month preceded by a history of intramuscular injection in the area. The patient had tachycardia (125 beats/min) and tachypnea (24 beats/min), NIBP was 110/78 mmHg. On systemic examination, he had induration and tenderness in the right gluteal region, which was extending up to the right popliteal fossa. He had active skin lesions in the form of pustules, vesicles, and bullae all over the body, more over the upper anterior chest, back, legs, oropharynx, and back involving the lumbar area as well. A diagnosis of necrotizing fascitis (right thigh) and active PV was made and urgent debridement was planned. Since patient had lesions all over the back, we planned general anesthesia. NIBP, HR, ECG, RR, and SpO2 were monitored. An intravenous access was achieved with 18G iv cannula on a lesion-free area.

He was premedicated with glycopyrrolate 0.2 mg, metoclopramide 10 mg, and fentanyl 80 μg. Anesthesia was induced with propofol 100 mg. Injection succinylcholine 100 mg iv was given to facilitate endotracheal intubation after ensuring bag mask ventilation. A very gentle direct laryngoscopy was done as the patient had oropharygeal and laryngeal mucosal lesions in the form of bullae and vesicles, which were very friable and started bleeding when laryngoscopy was tried. After inflating the cuff of the TT, the oropharynx was packed with wet gauge pack to stop the bleeding and to prevent aspiration into the trachea. Anesthesia was maintained on O2:N2O of 33:67, propofol infusion was titrated according to the anesthetic requirements of the patient. Neuromuscular blockade was achieved with injection vecuronium. The patient was put in the lateral decubitus position, pressure points padded, and surgery commenced. The procedure went on for 1 h and 15 min. The patient remained hemodynamically stable. At the end of surgery, after achieving a good spontaneous respiratory effort, neuromuscular blockade was reversed with injection neostigmine 2.5 mg and injection glycopyrrolate 0.4 mg iv. Gentle oropharyngeal suction was done, the pack removed and the patient was extubated successfully without much difficulty.

Postoperatively, the patient was put on injection hydrocortisone hemisuccinate 100 mg/day in consultation with the dermatologist and shifted to prednisone later.

Case 3

A 74-year-old woman, a known case of PV for the past 12 years, presented for fixation of intertrochanteric fracture of femur. She was on prednisolone 10 mg a day for the past 8 years. On preanesthetic assessment, no other comorbidity was noted apart from effort intolerance to climbing a single flight of stairs. She had numerous bullous lesions, active as well as chronic healed, over the arms and upper torso including buccal mucosal lesions. Skin over the lumbar spine was spared. Hemoglobin, coagulation parameters, renal function, ECG, and chest radiography were normal. Dobutamine stress echocardiography was negative for inducible myocardial ischemia. Skin consultation was sought. In the operating room, 18G intravenous cannula was inserted over the dorsum of left hand as it was free of any lesion. Injection hydrocortisone hemisuccinate 25 mg was given iv. Prednisolone impregnated gauze pieces were applied below the blood pressure cuff. After preloading with 600 mL of lactated Ringer's solution spinal anesthesia was administered through the L3–L4 interspace with 27G Quincke's needle after taking all the aseptic precautions. Two milliliters of preservative-free 0.5% heavy bupivacaine was deposited in the subarachnoid space. All the pressure points were adequately padded and due care was taken to avoid trauma to skin during traction and countertraction. Utmost care was taken while shifting the patient to the recovery room to avoid any trauma or pressure. Postoperative period was uneventful.

Case 4

A 63-year-old male presented to emergency room with blunt abdominal trauma after he met with a road traffic accident. He was diagnosed to have a ruptured splenic artery with continuous bleeding into the lesser sac. History revealed that he was suffering from diabetes mellitus and PV. On examination his blood pressure (BP) was 84/60 mmHg and a HR of 112 beats/min. He had numerous papulopustular bullous lesions over the trunk, arms, and back, including oral cavity lesions. Immediate resuscitation was started in the emergency room after achieving an 18G cannula over the lesion-free area with colloids till packed red blood cells were available. He had a hemoglobin of 7.8 gm%. Arterial blood gas showed pH of 7.33, pCO2 32, pO2 124 on venturi mask at FiO2 of 0.6, HCO3– 16 and lactate level of 4.5. His blood sugar was 156 mg/dL. He was immediately wheeled into the operation theater after the diagnosis was made. Continuous ECG, invasive BP, SpO2, and urine output were monitored intraoperatively. Intravenous hydrocortisone 25 mg along with glycopyrrolate 0.2 mg and morphine sulfate 5 mg was given. The patient was induced with titrated doses of thiopentone sodium till the loss of eyelash reflex. Cricoid pressure was applied by the assistant. After checking the ability to ventilate injection succinylcholine 75 mg iv was given and trachea was intubated with 8.0 mm cuffed tube. Cricoid pressure was released on confirmation of correct tube placement by bilateral chest auscultation. Direct laryngoscopy was done by senior anesthesiologist keeping in mind the active oral lesions. The patient was maintained on titrated isoflurane and vecuronium bromide and O2/air. Surgery lasted for 2 h. Intraoperative blood loss reached to 1800 mL, which was replaced with 3 units of packed red cells and 700 mL colloids. The patient was reversed with 2.5 mg of neostigmine and 0.4 mg glycopyrrolate and trachea extubated when spontaneous tidal volume of at least 450 mL was achieved. Postoperative course was uneventful. The patient was put on 100 mg hydrocortisone per day advised by skin consultant till the patient was allowed orally and then he was put on prednisolone 10 mg once daily. He was discharged on 10th day.

DISCUSSION

PV is a rare autoimmune disease characterized by vesiculobullous lesions and blisters involving the epidermis and mucous membranes. PV constitutes 70% cases of all pemphigus, although other forms such as pemphigus foliaceous, paraneoplastic pemphigus, and IgA pemphigus are also known to occur.

The physical cause of these lesions was first noted by Auspitz in 1880 as acantholysis. It involves immunoglobulin G autoantibodies directed against keratinocytes resulting in loss of intercellular adhesions.[1] When these patients present for surgery, they pose various challenges to the anesthesiologist as skin involvement hinders with vascular access and various monitoring techniques and also airway instrumentation may be heralded by the involvement of the oropharyngeal and laryngeal mucous membranes. Autoimmunity and steroid dependence is another issue to be taken care of.

Preoperative preparation of patients with PV consists of care of lesions, assessment of airway, and consequences of treatment. Corticosteroids should be continued perioperatively to prevent addisonian crisis from adrenocortical insufficiency in steroid-dependent patients. Daily cortisol production ranges from 9 to 11 mg/ m2/ day.[2] Stress causes adrenocorticotropic hormone–mediated increase in the cortisol production. During the perioperative period, it can go up depending on the severity, duration of surgery, and the technique and depth of anesthesia. Patients on supplemental steroid therapy cannot mount this response and hence candidates for “stress dosing” of glucocorticoids.

Dehydration and dyselectrolytemia is common in patients with painful and cicatricial oral lesions, owing to decreased intake and assessment of volume status is an important preanesthetic consideration.[3]

Evidence of the diseases associated with paraneoplastic pemphigus, such as rheumatoid arthritis and myasthenia gravis must be sought and recognized in the preoperative assessment. Each of this condition requires additional considerations as regards preoperative optimization and also intraoperative anesthetic management.[4]

Skin consultation may be sought for optimizing the therapy, induction of remissions, and to tide over the acute phases.

Koebner's (isomorphic) phenomenon, wherein patients with certain skin diseases, such as vitiligo, psoriasis, lichen planus, and so on, new identical skin lesions develop at the site of trauma to otherwise normal skin. This has also been reported in PV.[5] Thus, careful placement of BP cuffs, ECG electrodes, intravenous cannulas is imperative. Application of steroid ointments at the lesions where handling is possible may be helpful.

Oropharyngeal mucosal lesions usually occur in 50%–80% of patients with PV.[6] Airway instrumentation is potentially hazardous in such patients in view of risk of ulceration, edema, and bleeding from these pre-existing bulla.[7] Cicatricial laryngeal lesions causing severe airway obstruction has been reported.[8] Whenever general anesthesia requiring a secure airway (intubation/laryngeal airway) is unavoidable, all protective measures shall be ensued. In patients with documented oral lesions putting in a tracheal tube is a safer technique over LMA for the risk of bleeding from intraoral lesions and aspiration. Bag mask ventilation should be gentle. Airway instrumentation should be cautious. Perioral scarring may restrict opening of the mouth. The use of indwelling temperature probes and stethoscopes should be avoided. Eyes should be protected with ointment and taping should be avoided. We used all these measures while manipulating the airways of our patients requiring tracheal intubation and avoided vigorous suctioning at the time of extubation.

No particular anesthesia technique has been recommended for patients with PV, but regional anesthesia wherever possible is the preferred technique in such patients. Due considerations should be taken while administering regional techniques. Strict aseptic precautions should be undertaken to avoid secondary infection of the denuded lesions. Pricking the skin at sites with bullous lesions is best avoided, fearing development of isomorphic lesions. Local infiltration is contraindicated because of the potential danger of sloughing.[9] Whatever the choice of anesthesia is, protection of pressure points and adequate padding forms the mainstay of management.

Management of patients is further complicated by drug therapy. Preoperative administration of steroids can lead to suppression of hypothalamus–pituitary–adrenal axis. This requires perioperative steroid coverage to avoid addisonian crisis.[10]

Use of neuraxial opioids, especially morphine, may lead to pruritus and thus provoking new eruptions.[11] Fentanyl is a better alternative as the pruritus, if any occurring as side effect, is of shorter duration.[12] Thiopentone should be avoided considering the possibility of porphyria in bullous skin lesions.[13]

PV is an autoimmune disease of skin, which can present serious issues when anesthesia is planned. Oral lesions are common and airway compromise is a serious issue. Many of the treatments can have issues with major organ systems and thus due consideration should be given to these preoperatively. Care of these patients should be extended to the postoperative period as well with utmost care of the existing skin lesions and drug therapy.