Case Presentation: 57-year-old male, with history of recurrent idiopathic hypothermic episodes, HFrEF on carvedilol, T2DM on no medication for 3 months, and stage 4 CKD, presented to the ED for altered mentation. Vitals were unremarkable except for hypothermia (86.4°F). Patient was hypoglycemic (62 mg/dL). WBC count was low (1.26 10^3/uL). Urine WBCs were elevated (31-50/HPF). Urine drug screen was negative for drugs of abuse/ethanol. Renal/liver function were impaired—specifically, BUN (67 mg/dL), creatinine (3.8 mg/dL), AST (119 U/L), ALT (136 U/L), and alkaline phosphatase (452 U/L). Serum albumin was low (2.0 gm/dL). Blood pH was 7.38. Patient was hyperkalemic (5.5 mEq/L) and hyperchloremic (113 mEq/L). Ammonia level was normal (25.7 umol/L).EEG did not detect any electrographic seizures, and non-contrast CT head revealed no acute abnormalities.With hypothermia and leukopenia, patient met criteria for systemic inflammatory response syndrome and was admitted to the ICU. Empiric antibiotics including IV metronidazole, vancomycin, and cefepime were initiated. Urine culture was positive for Proteus vulgaris, and vancomycin and metronidazole were discontinued. Warming blanket was initiated to treat hypothermia. TSH was normal (3.18 mU/L), cortisol was normal (15.7 ug/dL), and blood creatinine peaked at 5.4 mg/dL. Persistent hypothermia was likely due to hypoperfusion from congestive heart failure and CKD.Following a literature review, patient’s carvedilol was held to achieve normothermia. Non-contrast pituitary MRI was unremarkable. Genetic lab workup, consisting of a plasma amino acid, urine organic acid, and acylcarnitine profile, did not reveal inborn error of metabolism. Two weeks later, clonidine 0.1 mg, cyproheptadine 2 mg, and clomipramine 25 mg were trialed to achieve normothermia. Clonidine was later discontinued due to hypotension, clomipramine was increased to 50 mg, and cyproheptadine was increased to 4 mg. Periods of hypothermia subsequently decreased.Renal function decreased, as indicated by increasing creatinine (5.6 mg/dL) and BUN (83 mg/dL). Hemodialysis three times weekly was initiated, and the patient no longer needed a warming blanket three days later. Mentation continuously improved. Three weeks later, patient was discharged with medication additions of clomipramine 50 mg and cyproheptadine 4 mg.

Discussion: Hypothermic patients should be evaluated for reversible conditions such as hypothyroidism, adrenal insufficiency, sepsis, and substance use. Hypothermia exacerbates hypotension, especially during the rewarming process, so blood pressure should be closely monitored. Beta-blockers and alpha-adrenergic agonists impair thermoregulatory processes and should be modified (1). Cyproheptadine and clomipramine, neuromodulatory regulators that act as serotonin-2A and histamine receptor antagonists, were effective in restoring normothermia in our patient (2). Scarce literature has hypothesized that uremic toxicity impairs thermoregulation, suggesting the utility of hemodialysis in achieving normothermia.

Conclusions: Recurrent primary hypothermia is rare but dangerous. Failure to manage hypothermia with appropriate pharmacotherapy leads to morbidities, such as delirium, a higher risk for acquired complications such as DVT/pneumonia, and deconditioning. In the right circumstances, neuromodulatory regulators, such as clomipramine and cyproheptadine, along with hemodialysis can help achieve prolonged normothermia and improved mentation.