Abstract
To the Editor:
We report the association of polyuria and severe hyperkalemia with TMPS use in a critically injured trauma victim. A 36-year old woman was involved in a motor vehicle crash and sustained severe closed head injury with frontal lobe intracerebral hemorrhage, multiple facial and skull fractures, as well as bilateral posterior arch fractures of C1 and an odontoid fracture. She had been taken by emergency medical services from the scene to an outside hospital, where she was intubated because of a Glasgow Coma Scale score (GCS) of nine. Thereafter, she was airlifted to our center. After initial stabilization, she underwent sequential operative repair of her facial and skull fractures and received clindamycin for perioperative prophylaxis. Her vertebral fractures were managed non-operatively.
She recovered slowly from her injuries but required both percutaneous tracheostomy and placement of a percutaneous endoscopic gastrostomy secondary to a persistently altered GCS, facial swelling, and a high-risk airway secondary to her cervical fractures. One week after admission, she developed pneumonia, which was treated empirically with doripenem, tobramycin, and vancomycin. She underwent bronchoalveolar lavage, and Stenotrophomonas maltophilia and Acinetobacter baumannii, both sensitive to TMPS, were isolated. Thus, TMPS was started at a dose of 224 mg q 6 h. Two days after initiation of TMPS therapy, the patient developed polyuria, and her serum potassium started to increase, peaking at 6.1 mg/dL (Fig. 1). Kayexalate and insulin were administered, and 40 mg of furosemide was given; however, the serum potassium concentration decreased only to 5.8 mg/dL. No evidence of myoglobinuria or compartment syndrome was present, and renal function (blood urea nitrogen/creatinine clearance) appeared normal. At this stage, TMPS was recognized as a potential cause of the hyperkalemia, the drug was stopped, and the serum potassium declined to 4.8 mg/dL. Her pneumonia had improved clinically, with improvement in her chest radiograph, temperature curve, white blood cell count, and PaO2:FIO2 (P:F) ratio. Additional doses of furosemide were given, and her serum potassium concentration normalized within 36 h. The patient's further hospital course was uncomplicated, and she was discharged to a rehabilitation facility one week after the event.
Serum potassium and urine output in trimethoprim sulfamethoxazole-induced hyperkalemia in young accident victim.
Development of hyperkalemia should be recognized as a potentially dangerous side effect of TMPS therapy [9–14]. Although this type of toxicity has been described most commonly as a consequence of high-dose intravenous TMPS, cases following oral therapy using low-dose TMPS also have been published [9, 11]. In one study, the incidence of this side effect was seven fold higher than with other antibiotics such as beta-lactams or fluoroquinolones [15]. Predisposing factors include renal failure, advanced age, use of angiotensin converting enzyme (ACE) inhibitors, and exposure to some drugs, such as spironolactone [15–17]. In the case presented here, hyperkalemia developed within 48 h after the start of drug exposure, which is earlier than in many published cases. However, numerous confounding treatments may contribute to a more rapid increase in potassium. Corticosteroids have been advocated to abrogate this specific side effect of trimethoprim, and fludrocortisone has been used as treatment of the condition [18]. However, Mohan et al. found that administration of prednisone, which also has some mineralocorticoid properties, was unable to prevent hyperkalemia in a series of HIV-positive individuals who received TMPS for Pneumocystis pneumonia [16]. As TMPS is increasingly used for CA-MRSA, Acinetobacter spp., and Stenotrophomonas maltophila infections, clinicians should be aware of this potentially life-threatening side effect.