DOI: https://doi.org/10.21203/rs.3.rs-1976368/v1
Background: Prescribing physicians must be aware of drug-drug interactions and exercise caution to prevent life-threatening electrolyte abnormalities. Here, we present a case of hyperkalemia-induced cardiac arrest in a patient treated with lisinopril with underlying chronic kidney disease and a recent course trimethoprim-sulfamethoxazole. We emphasize the need for awareness and vigilance when reconciling medications to thwart life-threatening consequences of even seemingly benign drug interactions.
Case presentation: A 55-year-old male was brought to the emergency room after being found unresponsive and pulseless for an unknown period due to cardiac arrest. Resuscitative efforts were successful in achieving return of spontaneous circulation after 15 minutes. In the emergency department, he was found to have a potassium level of 6.9. Further history obtained from the medical proxy revealed that the patient recently completed a course of trimethoprim-sulfamethoxazole, and he had underlying past medical history of chronic kidney disease and hypertension requiring treatment with lisinopril. The patient was subsequently transferred to the intensive care unit for neuroprognostication after arrest, continuous renal replacement therapy, and pressor support. Workup to investigate other causes of his arrest was unremarkable, leaving drug-induced hyperkalemia as the leading diagnosis made by exclusion.
Conclusions: We underscore the need to recognize drug interactions when prescribing new medications and the potential complications they may have in patients with particular risk factors. In this case, our patient had underlying chronic kidney disease and hypertension requiring management with lisinopril. The addition of TMP-SMX precipitated life-threatening hyperkalemia which caused his cardiac arrest. We underscore the importance of preventing dangerous arrhythmias through detailed medication reconciliations and diligence when prescribing new medications to prevent adverse interactions.
Trimethoprim-sulfamethoxazole (TMP-SMX) is a common bactericidal antibiotic used to treat a multitude of infections. Renin-angiotensin-aldosterone system (RAAS) inhibitors, often used to treat hypertension and heart failure, can predispose patients to hyperkalemia by inhibiting aldosterone secretion. Due to the widespread use of both TMP-SMX and RAAS inhibitors in the general population, coadministration is not uncommon. Prescribing physicians must be aware of drug-drug interactions and exercise caution to prevent life-threatening electrolyte abnormalities. The medical literature contains numerous examples of hyperkalemia induced by interactions from antibiotics and RAAS inhibitors. We share a unique clinical case of hyperkalemia-induced cardiac arrest precipitated by trimethoprim-sulfamethoxazole and lisinopril in a patient with additional predisposing risk factors. We underscore the need for detail-oriented medication reconciliations and awareness of drug-drug interactions to prevent dangerous electrolyte derangements.
An unresponsive 55-year-old man presented to the Emergency Department (ED) with a reported cardiac arrest after being found down for an unknown period of time. Chest compressions and endotracheal intubation were performed by first responders. Return of spontaneous circulation was achieved after 15 minutes. His records indicated a past medical history of type 2 diabetes mellitus on metformin, hypertension on lisinopril, stage 5 chronic kidney disease (CKD) not on dialysis, and recent treatment with trimethoprim-sulfamethoxazole (TMP-SMX) therapy for an ear infection. Further work-up in the hospital revealed the following labs: potassium of 6.9 mEq/L, lactic acid of 11.4 mmol/L, bicarbonate of 11 mEq/L, anion gap of 37 mEq/L, creatinine of 17.18 mg/dl, and CK 663 U/L. ECG showed sinus tachycardia with peaked T waves. His urine drug and ethanol levels were unremarkable, and a non-contrast head CT scan showed no acute intracranial abnormalities. CT scan of the chest and the abdomen/pelvis demonstrated no acute findings. Transthoracic echocardiography showed a left ventricular ejection fraction of 60% with no regional wall motion abnormalities, valvular disease, or pericardial effusions. Temporizing measures for hyperkalemia were started with intravenous calcium gluconate, insulin, and dextrose. He was subsequently transferred to the intensive care unit for neuroprognostication, continuous renal replacement therapy, pressor support, ventilatory support, and further investigation of the cause for arrest.
Hyperkalemia is a clinically significant derangement with the potential to cause muscle weakness, paralysis, cardiac conduction abnormalities, and arrhythmias [1]. The most common drugs known to precipitate hyperkalemia include antibacterials, renin-angiotensin-aldosterone system (RAAS) inhibitors, potassium-sparing diuretics, beta-blockers, non-steroidal antiinflammatory drugs, and digoxin [1, 2]. TMP-SMX is a bactericidal antibiotic known to predispose to hyperkalemia through the blockade of collecting tubule sodium channel. Hyperkalemia due to high dose TMP-SMX is often observed in HIV patients being treated for Pneumocystis jirovecii infection but is also known to cause symptomatic hyperkalemia in individuals without HIV when administered at standard doses [3, 4]. In fact, sudden death due to hyperkalemia has been reported in elderly patients receiving a combination of TMP-SMX with other predisposing medications [5, 6].
RAAS inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), are frequently used to treat heart failure and hypertension. Through inhibition of aldosterone secretion, these medications can also increase the risk for hyperkalemia. As such, coadministration of medications like TMX-SMX and ACE inhibitors cumulatively increase the risk for life-threatening electrolyte derangements. Antoniou et al. identified over 4,000 admissions due to hyperkalemia and observed a 7-fold increase in the risk of hyperkalemia with TMP-SMX as compared with beta-lactam antibiotics among elderly patients receiving RAAS inhibitors (odds ratio, 6.7; 95% CI, 4.5–10.0) [4]. Another prospective randomized study found a statistically significant increase in serum potassium in patients treated with TMP-SMX, compared to other antibiotics, with the rise taking place after five days of treatment in conjunction with ACE inhibitors and ARBs [4].
We highlight the awareness that providers must have for drug interactions and the caution they must exercise when reconciling medications. Unfortunately, our patient was prescribed TMP-SMX with underlying risk factors which likely precipitated hyperkalemia, including type 2 diabetes mellitus, stage 5 CKD, and hypertension requiring lisinopril treatment. After ruling out other causes of cardiac arrest in our patient, including hypovolemia, hypothermia, tamponade, pneumothorax, toxin overdose, acute coronary syndrome, arrhythmia, intracranial pathology, and infection, we attributed his cardiac arrest to hyperkalemia as a diagnosis of exclusion supported by his medical risk factors, medication interactions, and his markedly elevated serum potassium, lactic acid, and anion gap. We conclude that increased awareness combined with the adoption of a comprehensive approach is imperative in the management of patients to avoid dangerous electrolyte anomalies.
Trimethoprim-sulfamethoxazole (TMP-SMX), Renin-angiotensin system (RAAS), Emergency department (ED), Chronic kidney disease (CKD), Continuous renal replacement therapy (CRRT), Angiotensin-converting enzyme (ACE)
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AS, NJ, and AK made substantial contributions to the conception and design of the work, acquisition, analysis, manuscript writing, and interpretation of data. CV approved the submitted version.
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