Nephrogenic sclerosing fibrosis (NSF) is a relatively rare disorder that presents almost exclusively in patients who have end-stage renal failure. The disorder was first described in patients undergoing hemodialysis or patients with a failing or failed renal allograft.1 Gadolinium exposure increases the risk of NSF in these patients, especially in those who receive peritoneal dialysis.2 Other factors associated with NSF have included the use of recombinant erythropoietin, although the association was weak.3 The predominant finding is a multisystem fibrosis that progressively leaves the individual incapacitated with extremity contractures. Diffuse fibrosis that involves vital organs and mucous membranes eventually evolves. Airway difficulties have not been reported with this disorder before this case report.
The patient was a 29-year-old African American woman who underwent cadaveric renal allograft transplantation in 1999 because of end-stage renal disease of undetermined etiology, probably due to diabetes mellitus. She subsequently developed a slow, progressive, chronic rejection of the allograft, which required resumption of hemodialysis in 1999. Her other comorbidities included superior vena cava syndrome and blindness of undetermined etiology. She had prior general anesthesia for 4 procedures, including renal transplant, cholecystectomy, and 2 vascular access procedures before 2005. A review of her anesthetic records revealed a Mallampati Grade 2 airway at each procedure. Each of the anesthetic records notated a Cormack-Lehane Grade 1 or 2 view upon direct laryngoscopy during each of the procedures. The last procedure that was performed was a vascular access approximately 6 months after the patient underwent magnetic resonance imaging of the head and spine using gadolinium contrast. During the course of the last intubation for general anesthesia, it was noted that a bougie was used, and the largest size endotracheal tube that could pass was a 7.0 mm, with some difficulty. The remaining procedures, which included vascular access procedures, were accomplished under local anesthesia and IV sedation.
The patient presented to the university hospital emergency department in August 2009 with increasing bleeding from her gingiva and mucous membranes and was diagnosed with promyelocytic leukemia on bone marrow biopsy. While undergoing her routine dialysis before induction chemotherapy, the patient became profoundly hypotensive to 60 mm Hg systolic and tachycardic to a heart rate of 140 bpm. The medical emergency team started IV fluids and norepinephrine to maintain arterial blood pressure. Septic shock was suspected. Blood cultures were obtained, and broad spectrum antibiotics were started while awaiting the availability of an intensive care unit bed. Because of progressive respiratory deterioration, the decision was made to intubate before transport to the medical intensive care unit. Using direct laryngoscopy, etomidate 16 mg was titrated slowly, and rocuronium 30 mg was given. Succinylcholine was not given because of a potassium level of 6.8 mEq/L. Despite seemingly adequate muscle paralysis and multiple maneuvers to increase mouth opening, it was limited to approximately 1.5 cm.
Direct laryngoscopy was difficult and attempted 3 times. The first view with a Macintosh 3 blade revealed a Grade 3 Cormack-Lehane view, with only the tips of the arytenoids showing. Passage of a bougie was attempted without success. Other attempts with Miller 2 and 3 blades revealed Grade 4 Cormack-Lehane views. A GlideScope Ranger was used but could not be optimally placed because of limited range of mandibular motion despite paralysis. A laryngeal mask airway (LMA) was placed, as mask ventilation was impossible, and adequate ventilation with acceptable oxygen saturation to 92% was obtained. An ear-nose-throat (ENT) surgeon was summoned, and the glottic and laryngeal structures viewed by fiberoptic bronchoscopy through the LMA were diffusely fibrotic. The ENT surgeon and anesthesiologists present jointly decided to create a surgical airway in the operating room (OR), given the anatomic distortion, presumably due to NSF. The patient was transported to the OR with adequate LMA ventilation and oxygenation, and a formal tracheostomy was performed. Fiberoptic bronchoscopy performed in the OR revealed evidence of aspiration of gastric contents. Despite maximum vasopressor support and appropriate empiric antibiotic therapy, the patient died 48 hours after the procedure as a result of overwhelming sepsis and septic shock. A postmortem examination revealed diffuse fibrosis of the brain, dura mater, pleura, heart, and respiratory system.
Nephrogenic sclerosing fibrosis is a relatively new disorder, with the first cases described during the period 1997 to 2000.4–6 As previously mentioned, the disorder almost exclusively occurs in patients with end-stage renal failure who are undergoing dialysis. The use of gadolinium contrast for magnetic resonance imaging increases the risk of developing NSF approximately 5- to 6-fold in patients with end-stage renal failure, and approximately 95% of all patients with NSF have received gadolinium contrast.7 Gadolinium is almost exclusively excreted by the kidney, with clearance ranging from 1.3 hours in healthy volunteers to 34 hours in patients with end-stage renal failure. More than 200 patients with NSF have been described in the literature, and there is an international registry for patients with NSF at Yale University.8
Patients with NSF will develop symptoms from 2 months to 15 years after initiation of dialysis therapy. Age, gender, race, duration of renal failure, and etiology of kidney disease play no role in the development of NSF.9 Peritoneal dialysis patients seem more susceptible to NSF after gadolinium exposure than patients with end-stage renal failure undergoing hemodialysis, but that relationship is still unclear. Epoetin alfa has been associated with the onset of NSF in patients with end-stage renal failure, particularly in those receiving higher doses of epoetin.10 Nephrogenic sclerosing fibrosis has been described in liver transplant patients with advanced renal disease or hepatorenal syndrome who had undergone even transient dialysis with normalization of renal function.11
Clinically, the patient with NSF has contracted and tight skin, leading to eventual development of lower and upper extremity contractures caused by muscle fibrosis. Diffuse fibrosis of the lungs and heart leads to cardiopulmonary compromise. Particularly, the diffusion capacity of carbon monoxide is reduced in these patients.1 Esophageal fibrosis has been described in one case report and may predispose the patient to chronic and often not silent aspiration and resulting pneumonia.12 Respiratory failure is a common feature due to fibrosis of the diaphragm. Large and small joint fibrosis is also present in patients with NSF. Nephrogenic sclerosing fibrosis is diagnosed by clinical history and punch skin biopsy. No current treatment for NSF has been proven effective, although one report demonstrated some improvement with plasmapheresis therapy.11
Our patient, who required emergent intubation, presented a surprisingly difficult airway. A review of her previous anesthetic records, which were unavailable to us at the time of her presentation, revealed what seemed to be a progressively difficult airway after the onset of NSF symptoms. The benefit of using a muscle relaxant for intubation of patients with NSF is somewhat arguable, and use of muscle relaxants did not improve conditions for intubation in our patient; therefore, we would recommend against their routine use. Reviews of any previous anesthetic records that are available are recommended before elective surgery.
We would recommend the use of an awake fiberoptic intubation technique and the availability of other airway devices because of the unpredictable condition of the glottis and mouth opening in these patients. Because of the possibility of esophageal dysfunction and aspiration, these patients should be considered as having full stomachs, and aspiration risk precautions should be observed. Furthermore, the use of smaller endotracheal tubes is recommended because of the unpredictable degree of fibrosis that may be present. We would also recommend that an ENT surgeon or other surgeon skilled at emergent tracheostomy or cricothyrotomy be present at the time of intubation.
In summary, we present the case of a young woman with NSF requiring tracheostomy for emergent airway security. As the number of patients with renal failure and a history of magnetic resonance imaging contrast continue to increase, the anesthesiologist called upon to secure the airway in these individuals should be alert to the possibility of a difficult airway.
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