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Emergency — Nephrology / Critical Care
32

Fever and Clonus in a Dialysis Patient

Serotonin syndrome, rhabdomyolysis, and a fluid decision that goes the wrong way

Presentation

A 64-year-old woman on maintenance hemodialysis (anuric, MWF schedule) is admitted with a tunneled-catheter infection. Blood cultures grow vancomycin-resistant Enterococcus, and infectious disease starts linezolid. Her outpatient medications include sertraline 100 mg daily for depression, amlodipine, and a phosphate binder.

Roughly 36 hours after the first linezolid dose, nursing calls: she is agitated, diaphoretic, and shivering.

Examination

Temp 38.9 °C · BP 178/104 · HR 122 · RR 24. She is tremulous and hyperreflexic, with sustained clonus at both ankles and greater rigidity in the legs than the arms. Pupils are dilated. CK 8,400 U/L, potassium 6.2 mmol/L, bicarbonate 16.

Questions

1

Which diagnosis best fits, and which single examination finding most supports it?

A) Neuroleptic malignant syndrome — supported by rigidity
B) Serotonin syndrome — supported by lower-limb-predominant clonus
C) Anticholinergic toxicity — supported by dilated pupils
D) Sepsis from the catheter infection — supported by fever and tachycardia
Correct Answer: B
Learning Point: Clonus is the discriminating finding, and it is characteristically worse in the legs than the arms. The Hunter Serotonin Toxicity Criteria use seven features — clonus (inducible, spontaneous, or ocular), agitation, diaphoresis, tremor, hyperreflexia, hypertonicity, and temperature above 38 °C — and are more sensitive and specific than Sternbach's criteria (84% vs 75%; 97% vs 96%). NMS produces lead-pipe rigidity with bradykinesia over days to weeks after a dopamine antagonist, not hyperreflexia and clonus in 36 hours. Anticholinergic toxicity produces dry skin and normal reflexes — she is diaphoretic and hyperreflexic. Sepsis does not cause clonus.
📚 Reference: Clinical Mastery: Psychotropic and ADHD Medications in Hypertension and CKD — Section 6.5
2

Which medication precipitated this, and by what mechanism?

A) Vancomycin, by direct neurotoxicity
B) Sertraline alone, from accumulation in renal failure
C) Linezolid, which is a reversible non-selective MAOI
D) Amlodipine, via a hypertensive interaction
Correct Answer: C
Learning Point: Linezolid is a reversible non-selective monoamine oxidase inhibitor — a fact routinely forgotten because it is filed mentally as an antibiotic. Combined with an SSRI it produces serotonin syndrome, and hypertensive crisis alongside serotonin syndrome after linezolid is documented. This is the realistic trigger on a renal service, because linezolid treats VRE and resistant MRSA in precisely the population most likely to be on an SSRI. Sertraline is not meaningfully renally cleared and had been stable for months.
📚 Reference: Lecture: Psychiatric & ADHD Medications and Blood Pressure
3

Her CK is 8,400 and rising. A resident orders 2 litres of normal saline wide open, citing rhabdomyolysis protocol. What is the problem?

A) Nothing — this is correct rhabdomyolysis management
B) She is anuric; there is no kidney to protect and nowhere for the fluid to go
C) Saline will worsen her hyperkalemia directly
D) Bicarbonate should be used instead to alkalinize the urine
Correct Answer: B
Learning Point: Aggressive volume expansion in rhabdomyolysis works by maintaining urine flow to limit myoglobin cast formation. In an anuric dialysis patient there is no residual function to protect and no urine to produce — the fluid has nowhere to go and buys pulmonary edema. Management is temperature and CK control plus urgent dialysis for the hyperkalemia and acidosis. D fails for the same reason: urinary alkalinization requires urine.
📚 Reference: Clinical Mastery: Psychotropic and ADHD Medications in Hypertension and CKD — Section 6.5
4

She is thrashing and difficult to control. Which intervention is CONTRAINDICATED?

A) Intravenous benzodiazepines
B) Active external cooling
C) Four-point physical restraints
D) Cyproheptadine
Correct Answer: C
Learning Point: Physical restraints are contraindicated. A patient straining against restraints generates isometric muscle contraction, which worsens hyperthermia, lactic acidosis, and muscle breakdown — the exact triad already injuring her. Chemical sedation with benzodiazepines is the correct control measure, alongside active cooling and cyproheptadine (a 5-HT2A antagonist) in moderate-to-severe cases. Dantrolene and bromocriptine treat other syndromes and have no role here.
📚 Reference: Student Handout — Section 6
5

Which of the following would NOT have been a plausible alternative trigger in this patient?

A) Fentanyl added for catheter-site pain
B) Ondansetron for nausea
C) Methylene blue given for vasoplegia
D) Amlodipine continued at her home dose
Correct Answer: D
Learning Point: Fentanyl, tramadol, methadone, ondansetron, and methylene blue are all serotonergic and can precipitate the syndrome in a patient already on an SSRI. Ondansetron is the most commonly missed because it is treated as a benign antiemetic and given reflexively. Amlodipine is a dihydropyridine calcium channel blocker with no serotonergic activity and is not implicated.
📚 Reference: Clinical Mastery: Psychotropic and ADHD Medications in Hypertension and CKD — Section 6.5

Take-Home

Two reflexes to build

1. Dorsiflex the ankle in any febrile, agitated patient on a serotonergic drug. Clonus makes the diagnosis and separates it from NMS and anticholinergic toxicity in seconds.

2. Reconcile the psychiatric list before the antibiotic is ordered, not after the pressure hits 220. Linezolid plus an SSRI is the version of this you will actually meet.

Protocols are written for patients who make urine. Before applying any volume-based algorithm — rhabdomyolysis, contrast nephropathy, tumour lysis — ask whether this particular patient has residual kidney function. In the anuric patient the protocol inverts.

Andrew Bland, MD, FACP, FAAP

Medical Associates Department of Nephrology · University of Illinois College of Medicine at Peoria · University of Dubuque PA & DPT Programs · Butler College of Osteopathic Medicine

Interactive teaching case · Psychotropic & ADHD Medications and Blood Pressure

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