Pseudosepsis caused by acute salicylate intoxication

Introduction: Chronic salicylate intoxication has been implicated as a cause of systemic inflammatory response syndrome (SIRS) through long-standing inhibition of regulatory eicosanoids.^1-3 This case represents the first report of acute salicylate intoxication manifesting as a sepsis-like syndrome with distinct correlations between the aspirin levels and the cardiovascular parameters. Case Presentation: A 19-year-old female with a history of orthotopic liver transplant secondary to sclerosing cholangitis presented to a local emergency room with right upper quadrant pain, vomiting and chills. She was chronically maintained on prednisone, cyclosporine, trimethoprim/ sulfamethoxazole and acyclovir. Her initial physical exam revealed a temperature of 98.8°F, heart rate of 130/min, blood pressure of 130/68 mm Hg and diffuse abdominal pain. Her initial laboratory data revealed a WBC of 15.6 k/μL (92% neutrophils), hemoglobin of 11 g/dl and platelet count of 244 k/μL. Sodium was 146 mmol/L, potassium 5.3 mmol/L, chloride 104 mmol/L, bicarbonate of 22 mmol/L, BUN 40 mg/dl, creatinine 2.8 mg/dl and glucose 98 mg/dl with an anion gap of 20. The patient was transferred to the University of Wisconsin Trauma and Life Support Center for further management. En route, the patient was noted to have coffee ground emesis, became unresponsive and sustained a respiratory arrest and required intubation. Physical exam on arrival revealed heart rate of 170, blood pressure of 80/40, respiratory rate of 18 and temperature of 105.5°F. Arterial blood gas analysis on an FiO2 of 100% showed a pH of 7.19, PaCO2 of 43 mm Hg, PaO2 of 321 mm Hg and HCO3 of 16 mmol/L. Repeat lab values were sodium 153, potassium 4.2, chloride 117, bicarbonate 16, BUN 29, glucose 152 and serum osmolality of 327 mOsm/L with an anion gap of 20 and an osmolar gap of 3 mOsm/L. Serum lactate and ketones were normal. The initial aspirin level was 64 mg/dl. Pulmonary artery catheterization was performed to determine the cardiovascular parameters. Initial hemodynamic values revealed a cardiac output (CO) of 19 L/min, systemic vascular resistance (SVR) of 200 dyne·;s/cm⁵ and pulmonary capillary wedge pressure of 11 mm Hg. Hemodialysis was initiated two hours after admission. This was associated with decline in aspirin level, improvement in cardiovascular stability, diminution in vasopressor requirement, resolution of metabolic acidosis, improvement in mental status and normalization of temperature. Serial aspirin levels (ASA), CO and SVR measurements are shown in the following table (time is approximate). After extubation, she admitted to having taken a large dose of aspirin in a suicidal attempt. She was discharged from the hospital on day #13 in a good condition. TIME (hours) 0 4 8 12 16 24 28 36 ASA (mg/dl) 64 66 37 17 16 14 6 CO (L/min) 19 13 11 7.5 9.5 7.3 7.9 7.9 SVR (dyne·s/cm⁵) 200 333 460 550 500 850 700 760 Linear regression analysis revealed strong correlation between ASA and CO (r=0.79, p=0.025) and ASA and SVR (r=-0.89, p<0.0001). Discussion: This case illustrates several important points. First, although her presentation was suggestive of sepsis in an immunocompromised host, evaluation of the anion gap metabolic acidosis led to the correct diagnosis. Second, chronic salicylate intoxication has been described as pseudosepsis syndrome. This patient illustrates that acute intoxication can present similarly. Third, the clinical manifestations/ hemodynamic profiles and their resolution were temporally related to the aspirin levels. Fourth, the linear correlation observed between ASA and CO/SVR confirms the effect of excessive aspirin in the hemodynamic pattern. Fifth, inhibition of regulatory eicosanoids with an increase in IL-6 and TNF-α has been implicated in hyperdynamic shock in chronic ASA intoxication.^2,3 The mechanism in acute intoxication, although possibly similar, remains undefined. Conclusion: Acute salicylate intoxication should be considered in the differential diagnosis of hyperdynamic shock with anion gap metabolic acidosis.