Management of the Hospitalized Patient Nephrology Cases Kerry C. - PDF document

Management of the Hospitalized Patient Nephrology Cases Kerry C. Cho, MD Associate Professor of Clinical Medicine Fellowship Program Director Division of Nephrology October 16, 2015 Case 1: Hyponatremia HPI: 49 yo M without significant medical hx had minor MVA 2 weeks prior to admission. He was the restrained passenger of a car when his car was rear-ended by another car. He had mild occipital trauma and brief LOC for an unclear duration, possibly minutes. At an OSH, he was evaluated, head CT was negative, and he discharged home with Norco, Flexeril, and Naproxen. Over the next two weeks, he had progressive nausea, vomiting, headaches, confusion, and difficulty concentrating. He came to ED at UCSF for evaluation. 2 1 10/26/2015 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Case 1, continued Physical examination  Temp 36.9°, Pulse 71, Resp 16, 135/93, O2 sat 98% RA, Wt 80 kg  Nystagmus with bilateral lateral gaze  Lateral chest wall contusions from seat belt Labs 118 86 13 glucose 94 serum osms 259 4.5 22 0.72 AG 10 LFT, TSH, cortisol negative Urine Na 99, Urine K 53 UA trace ketones 3 Case 1, continued ED Course  Given 1 L normal saline in ED, Na decreased from 118 to 117  Repeat Head CT negative Admitted to medicine service  Initiated on 3% hypertonic saline at 40 mL/hour, free water restricted  Na corrected to 125 mEq/L, HTS d/c, Na dropped to 120.  I/O not adequately recorded  Nephrology consulted for persistent hyponatremia  Neurology consulted for nystagmus 4 2 10/26/2015 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

What is 0.9% and 3% Saline? Normal Saline  154 mEq/L of NaCl  0.9% = 0.9 g/dL = 0.9 g per 100 mL = 9 g/L  2 gram per day Na diet = 5 grams NaCl Hypertonic Saline  513 mEq/L of NaCl  3% = 3 g/dL = 3 g per 100 mL = 30 g/L 5 Basic Nephrology for Hospitalists Electrolyte Free Water Clearance (EFWC)  EFWC = Urine Flow x [1 – (U Na + U K /P Na )] where U Na + U K are urine concentrations, and P Na is plasma [Na] Implications of (U Na + U K ) > P Na  Free water restriction will not work  Hypertonic saline will likely be necessary to prevent desalination with retention of free water  Consider nephrology consultation 6 3 10/26/2015 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

“Safe” Serum Sodium Correction Fast and Slow correction Symptomatic/severe hyponatremia  FAST correction  Raise serum Na 4-6 mEq/L within 6 hours  Consider 3% HTS bolus 50-100 mL IV  Goal correction rate: 4-6 mEq/L and ≤ 8 mEq/L over any 24 hour period Chronic severe hyponatremia with mild/moderate symptoms: SLOW  HTS AND desmopressin 1-2 mcg IV/SQ q 8 hrs for 24 to 48 hours*  Desmopressin prevents unanticipated water diuresis from reversible cause of ADH release. Contraindicated in patients who cannot adhere to water restriction 7 General Advice for Hypertonic Saline in Hyponatremia Mgmt Hypertonic Saline  Rule of thumb: HTS infusion rate is typically <0.5 mL/kg/hour  If > 0.5 mL/kg/hour, then you either made a mathematical error or you’re correcting the serum Na too quickly.  Consider nephrology consultation Severe Symptomatic Hyponatremia  Na < 120 mEq/L typically acute (< 48 hours) OR hyponatremic patients who cannot tolerate increased ICP  3% HTS 100 mL IV q 10 mins prn, up to 2-3 total doses  Goal: rapid correction of hyponatremia by 4-6 mEq/L 8 4 10/26/2015 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Treatment of Osmotic Demyelination or Na Correction Rate > 8 mEq/L per 24 hr  D5W at 6 mL/kg lean body weight IV over two hours, repeat prn  Desmopressin 2 mcg IV/SQ q 6 hours  Goal: drop serum Na by 1 mEq/L per hour to original target Na • Example: Initial Na 110 mEq/L, original goal Na 116 mEq/L, actual Na 125 mEq/L. • Treatment with D5W and desmopressin should return Na to 116 mEq/L over about 8-10 hours  Limitations: rat model, case reports in humans; ideal goal Na and rate of correction undefined. 9 Hospital Course, continued Hyponatremia  3% Hypertonic restarted at 40 mL/hour, Na checks q 2-3 hours  Na reached 125 mEq/L, 3% HTS d/c, Na returned to 120 with next lab draw  Urine output never adequately recorded  Pt insistent that free water restriction followed Nystagmus  Labyrinthine dysfunction given +head thrust to R and gaze evoked nystagmus to L, probable labyrinthine concussion  Hyponatremia likely related to TBI, recommended MRI 10 5 10/26/2015 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Hospital Course, continued Brain MR  Multiple areas susceptibility in the left occipital lobe, likely due to age indeterminate microhemorrhages, possibly traumatic. With recurrent hyponatremia off HTS, tolvaptan 15 mg PO given once  Na corrected 6-8 mEq/L over first 24 hours  Second dose of tolvaptan 15 mg the following day, observed overnight then discharged.  Required 2-3 additional doses of tolvaptan over next two weeks at outpatient  Na normalized on labs 2, 3, and 6 weeks post-discharge 11 ADH receptor antagonists: Vaptans Three receptors for vasopressin/ADH  V1a - vasoconstriction  V1b - ACTH release  V2 - antidiuretic response Vaptans – ADH receptor antagonists  V2R specific: tolvaptan, mozavaptan, satavaptan, and lixivaptan (only tolvaptan available in the US)  Conivaptan: V2 and V1a antagonist, IV formulation, available in US  True aquaretics/diuretics, not natriuretics: free water loss with neutral effect on Na balance 12 6 10/26/2015 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Tolvaptan Information Dosages, Indications and Adverse Effects  15 and 30 mg tablets available in US  Tablets > 30 mg available outside US; 45, 60, and 90 mg tablets  Not approved for usage in symptomatic/severe hyponatremia  Poorly tolerated chronically due to aquaresis, nocturia, thirst, dry mouth  Limited data on clinical outcomes and long term outcomes  May result in overrapid correction of serum Na, especially if used inappropriately. 13 Tolvaptan Information FDA Warning  Should not be used for longer than 30 days  Contraindicated in patients with liver disease (including cirrhosis)  Higher incidence of increased AST and ALT (0.9% in tolvaptan group vs. 0.4% in placebo group) in Tempo 3:4 ADPKD trial, NEJM 2012;367(25):2407. 14 7 10/26/2015 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Practical Advice on Vaptans  Start with tolvaptan 15 mg PO x 1, first dose during daytime  D/C exogenous sources of Na (NaCl tablets, normal saline, hypertonic saline)  D/C free water restriction: thirst and access to free water protect against overly rapid correction of serum [Na]  Repeat serum [Na] within 4-6 hours of first dose • Onset of action 2-4 hours, peak action 4-8 hours  Expensive (list price $400 per tablet)  Consider nephrology consultation 15 Teaching Points  MVA and traumatic brain injury  hyponatremia  (U Na + U K ) > P Na  Free water restriction will not be effective, consider hypertonic saline  Consider nephrology consultation if you are considering hypertonic saline, ddAVP, or tolvaptan use  Tolvaptan: Stop exogenous Na intake and free water restriction, monitor serum Na closely 16 8 10/26/2015 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Case 2 Reason for Consultation: increased osmolar gap 62 yo WM hx morbid obesity, OSA, CHF presents with several year hx of malaise, weakness, dizziness, and head/hand tremor over the last several years, worsening over the last few weeks. He is a difficult historian with inappropriate affect, delusions, grandiosity, and confabulation. Case 2 Medical History  Morbid obesity  Obstructive sleep apnea  Congestive heart failure  Atrial fibrillation  Parathyroid carcinoma s/p PTX  Kidney stones  CKD, creatinine 2.0-2.6  Hypothyroidism 9 10/26/2015 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Case 2, continued Medications Allergies:  KCl 8 mEq day Cefazolin  HCTZ 25 mg daily Dilantin  Amiodarone 200 mg daily PCN  Synthroid 125 mcg daily  Metoprolol 100 mg daily  Furosemide 20 mg daily  Atorvastatin 10 mg daily  Coumadin  Vitamin C Case 2, continued Family Hx: Non-contributory Social Hx  Lives at home with a friend, formerly homeless.  Worked for the British Royal Family  Doctorates in criminology and business, master degree in business administration and social psychology  Former UC Berkeley professor 10 10/26/2015 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Case 2, Health-related behaviors  Former smoker with 7 pack-years  No EtOH or drugs. Review of Systems  Dizziness, weakness, feeling of impending doom, uneasiness, insomnia, anhedonia, depression Case Presentation Physical Exam 36.5 158/92 65 18 99% RA HEENT normal Cardiac normal Chest normal Abdomen obese, otherwise normal Ext trace pitting edema Skin abrasion over RLE, no rash Psych grandiosity 11 10/26/2015 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]