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L WESLEY ALDRED, MD; MELANIE MCCAULEY, MD; JASON PICKETT; CONNELL KNIGHT; MOHAMMAD ULLAH, MD UNIVERSITY OF MISSISSIPPI MEDICAL CENTER Hypophosphatemia.

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Presentation on theme: "L WESLEY ALDRED, MD; MELANIE MCCAULEY, MD; JASON PICKETT; CONNELL KNIGHT; MOHAMMAD ULLAH, MD UNIVERSITY OF MISSISSIPPI MEDICAL CENTER Hypophosphatemia."— Presentation transcript:

1 L WESLEY ALDRED, MD; MELANIE MCCAULEY, MD; JASON PICKETT; CONNELL KNIGHT; MOHAMMAD ULLAH, MD UNIVERSITY OF MISSISSIPPI MEDICAL CENTER Hypophosphatemia Masquerading as Meningitis

2 Objectives Review the causes of altered mental status Illustrate the importance of revisiting your differential diagnosis in the face of treatment failure Discuss how bisphosphonates contributed to this case Examine the signs and symptoms of hypophosphatemia

3 History 68 yo WF with RA and osteoporosis found unresponsive Found with fentanyl patch in place Some response to naloxone Complained of HA and stated that “pirates attacked [her] ship” Home medicines: fentanyl patch, alprazolam, butalbital- ASA-caffeine-codeine

4 Physical Exam VS: T 99.6, RR 22, BP 140/90, HR 105 C-collar in place Photophobia

5 Initial Differential Diagnosis Meningitis Drug overdose Intracranial lesion Electrolyte abnormalities

6 Investigations WBC 21.4 UDS: +benzodiazepines, +opiates, +barbiturates Acetaminophen <15 mcg/mL, salicylate <1 mg/dL, alcohol <10 mg/dL Na+ 130, K+ 2.9, Ca Urinalysis negative for UTI

7 Investigations

8 Lumbar puncture attempted by two physicians but unsuccessful

9 Initial Differential Diagnosis Meningitis  SIRS+, CXR negative, UA normal Drug overdose  Acute drug overdose vs chronic polypharmacy Intracranial lesion  No large masses, no acute hemorrhage  No focal deficits to suggest ischemic event Electrolyte abnormalities  Mild hyponatremia, hypokalemia  Take note, no Mg or Ph at admission

10 Hospital Course Admitted for sepsis secondary to meningitis Started on ceftriaxone, vancomycin, and ampicillin Hospital day 2: witnessed seizure activity, resolved with lorazepam Hospital day 3: developed vertical nystagmus and remained confused

11 Hospital Course Full electrolyte panel ordered given new nystagmus K+ 2.5 mmol/L, Ca mg/dL, Mg 1.6 mg/dL, Ph 0.6 mg/dL Follow-up PTH found to be pg/mL Replaced electrolytes  hospital day 4: nystagmus and confusion resolved

12 Hospital Course Blood cultures negative Patient afebrile WBC trending down Hospital day 4: d/c antibiotics with continued improvement

13 Chart Review IV infusion of zoledronic acid 3 days prior to admission

14 Discussion Causes of altered mental status  Meningitis  SIRS+, photophobia, CSF unable to be obtained  Drug overdose  Fentanyl patch, benzodiazepines, barbiturates  Responded to naloxone  CNS lesion  s/p fall; CT head negative for bleed  No focal deficits to suggest ischemic event  Electrolyte abnormalities  Not investigated thoroughly enough at admission

15 Discussion Pathogenesis of hypophosphatemia after zoledronic acid infusion  Zoledronic acid  dec Ca++  2° hyperPTH  dec reabsorption of PO4 in proximal tubule  Decreased osteoclastic activity leads to decreased release of PO4 from bone compartment into serum

16 Discussion SIRS and hypophosphatemia  Hypophosphatemia associated with cardiac arrhythmias  Hypophosphatemia shown to decrease diaphragmatic strength  Hypophosphatemia associated with leukocyte abnormalities

17 Discussion Neurologic manifestations of hypophosphatemia  Metabolic encephalopathy resulting from ATP depletion  Mild irritability  Paresthesia  Generalized seizures  Coma

18 When All Else Fails… Blame the bisphosphonate

19 References Maalouf NM, Heller HJ, Odvina CV, Kim PJ, Sakhaee K. Bisphosphonate- induced hypocalcemia: report of 3 cases and review of literature. Endocr Pract. 2006; 12 (1): Rosen CJ, Brown S. Severe hypocalcemia after intravenous bisphosphonate therapy in occult vitamin D deficiency. N Engl J Med. 2003; 348 (15): Silvis SE, DiBartolomeo AG, Aaker HM. Hypophophatemia and neurological changes secondary to oral caloric intake: a variant of hyperalimentation syndrome. AM J Gastroenterol. 1980; 73 (3): Subramanian R, Khardori R. Severe hypophosphatemia. Pathophysiologic implications, clinical presentations, and treatment. Medicine (Baltimore). 2000; 79 (1): 1-8. Kennel K, Drake M. Adverse effects of bisphosphonates: implications for osteoporosis management. Mayo Clinic Proc. Jul 2009; 85 (7): Liamis G, Milionis HJ, Elisaf M. Medication-induced hypophosphatemia: a review. QJM. 2010; 103 (7):


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