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10/23/2010

Objectives
Physiology
Risk factors for hypocalcemia
Management strategies
Passive vs. active

Head and Neck


Endocrine Surgery
Department of
Otolaryngology Head and
Neck Surgery

Treatment of hypocalcemia

Management of Calcium in Thyroid


and Parathyroid Surgery

Ted H. Leem, MD MS
Assistant Professor
Division of Head and Neck Oncology
Otolaryngology
Head and Neck
Surgery

October 23, 2010

Physiology

Calcium Homeostasis via PTH

Calcium is the most abundant mineral


~ 1% is found in plasma
bound to proteins
ionized

Functions
Bone and teeth
Nervous system
Muscular tone and contraction
Clotting cascade

Regulated by Parathyroid Hormone (PTH)


Otolaryngology
Head and Neck
Surgery

Otolaryngology
Head and Neck
Surgery
Kronenberg: Williams Textbook of Endocrinology, 11 ed.

10/23/2010

Post-surgical Hypocalcemia

Risk factors for hypocalcemia

Hypoparathyroidism

Thyroid surgery

paresthesias, cramps, mental status changes, tetany,


EKG changes

Total vs. subtotal


Malignancy, goiter

Most commonly reported complication

Reoperative procedures

Similar rates for thyroid and parathyroid surgery

Central neck dissection

Temporary 10%-40%

Parathyroid surgery

Permanent 1%-3%

Adenoma vs. hyperplasia


Markedly elevated preoperative PTH

Who is at risk?

Previous surgery
Renal hyperparathyroidism

Otolaryngology
Head and Neck
Surgery

Otolaryngology
Head and Neck
Surgery
Complications of Thyroid Surgery. In Complications of Head and Neck Surgery. Ed Eisele D. and R. Smith. 2nd ed. 2009
Complications of Parathyroid Surgery. In Complications of Head and Neck Surgery. Ed Eisele D. and R. Smith. 2nd ed. 2009

3 Approaches Following Surgery

Wait and See

Spectrum of Passive to Active

If it aint broke, dont fix it


Treat only when hypocalcemia develops
Serial blood draws
Majority of hypocalcemia develops within 24 hours but
can be as late as 72 hours

Increase length of hospitalization

Wait and
see

Otolaryngology
Head and Neck
Surgery

Selective
treatment

Costly

Empiric
treatment

Otolaryngology
Head and Neck
Surgery

10/23/2010

Monitoring Calcium
Serum calcium measurements
Most common
Correct for hypoalbuminemia
Add 0.8 for every 1g/dL of albumin that is missing
0.8[4 (g/dL) - albumin (g/dL)] + Ca (mg/dL)

Affected by acid-base disorders

Measured serum calcium 6h and 12h postoperatively

Cheaper

If calcium increased, 0% hypocalcemia

Ionized calcium

Calcium was stable or decreased, 70%


hypocalcemia

Sick patients
Calcium drip

< 8 mg/dL at 12h  75% developed hypocalcemia


> 8 mg/dL at 12h  13% developed hypocalcemia

Special handling
Otolaryngology
Head and Neck
Surgery

Otolaryngology
Head and Neck
Surgery

Costly
Calvi LM, Bushinsky DA. When is it appropriate to order an ionized calcium? J Am Soc Nephrol. 2008. Jul;19(7):1257-60.

Nahas et al. Laryngoscope 2006.

Serum Calcium
Serum Calcium is adequate to monitor for
hypocalcemia
Using this algorithm
Safe and early discharge
Decrease hospital stays

Otolaryngology
Head and Neck
Surgery

Otolaryngology
Head and Neck
Surgery
Nahas et al. Laryngoscope 2006.

10/23/2010

Selective Treatment

PTH and Calcium

Predicting what/who will break

Perioperative PTH levels have been shown to be


predictive of hypocalcemia

Identifying those at risk for symptomatic or


severe hypocalcemia

Sensitivity and specificity have been suboptimal


Timing and cutoff values variable

Risk stratifying based on calcium and PTH

Different labs and assays

Treat prophylactically with calcium +/- Vitamin D

Evaluated pooled data from 3 studies


Looked at PTH and calcium at 1h 6h post-op

Otolaryngology
Head and Neck
Surgery

Otolaryngology
Head and Neck
Surgery
Jumaily JS et al. Prediction of hypocalcemia after using 1- to 6-hour postoperative PTH and calcium levels. Head Neck. 2010 Apr;32(4):427-34.

PTH and Calcium

PTH and Calcium

PTH levels 1h 6h after surgery was predictive

1 and 6 hours allows for early prediction

60% reduction

Outpatient surgery

When combining 60% reduction in PTH with a


10% decline in serum calcium at 6 hours

Decreased duration of inpatient stay


Cost savings

100% sensitivity
100% specificity
100% positive-predictive value

Not statistically different than using PTH values


alone at 1h 6h post-operatively

Otolaryngology
Head and Neck
Surgery

Otolaryngology
Head and Neck
Surgery
Jumaily JS et al. Prediction of hypocalcemia after using 1- to 6-hour postoperative PTH and calcium levels. Head Neck. 2010 Apr;32(4):427-34.

Jumaily JS et al. Prediction of hypocalcemia after using 1- to 6-hour postoperative PTH and calcium levels. Head Neck. 2010 Apr;32(4):427-34.

10/23/2010

UCLA Protocol

Which PTH Assay


Depends on your local resources
Specialized training
Lab timetables
Standard and rapid PTH have been shown to be
highly correlated

Otolaryngology
Head and Neck
Surgery

Otolaryngology
Head and Neck
Surgery
Wiseman JE et al. An algorithm informed by the PTH level reduces hypocalcemic complications of thyroidectomy. World J Surg. 2010 Mar;34(3):532-7.

Prophylactic Treatment
Pre-emptive calcium, vitamin D, or both can
decrease the risk for hypocalcemia
Moore. J Am Coll Surg 1994;178:11-6

n = 706

Bellantone et al. Surgery 2002;132:1109-12


Seybt M and Terris D. Laryngoscope 2010;
120:959963, 2010

Control
72

Motivated by short stay or outpatient surgery

Calcium
288

Calcium + Vitamin
D
346

Non-randomized, observational
Hypocalcemia
31%
Otolaryngology
Head and Neck
Surgery

Hypocalcemia
19%

Hypocalcemia
4%

Otolaryngology
Head and Neck
Surgery
International Journal of Surgery. 2010

10/23/2010

Empiric Treatment

Treatment

Reduce the rates of hypocalcemia

Its broken, now what?


Calcium

May allow for early discharge

Vitamin D

Same day discharge

Safe

Magnesium

Patient counseling is extremely important

PTH

Cost savings
Protocols vary
3g Calcium carbonate/day
Vitamin D vs. calcitriol
Otolaryngology
Head and Neck
Surgery

Otolaryngology
Head and Neck
Surgery

Treatment

Oral Calcium

Goal: low-normal

Greatest absorption with doses < 500 mg

Severe hypocalcemia

Large doses may cause

IV Calcium gluconate
peripherally

Gas
Bloating

Bolus vs. drip

Constipation

Symptomatic
hypocalcemia
IV or PO
2 g 10 g of elemental
calcium divided BID or
TID

Otolaryngology
Head and Neck
Surgery

Lin C-Y et al. Surg Today. 2007

Walker Harris V, Jan De Beur S . Postoperative hypoparathyroidism. Thyroid. 2009 Sep;19(9):967-73.

Otolaryngology
Head and Neck
Surgery
Office of Dietary Supplements. Nih.gov 2010

10/23/2010

Calcium Preparations

Otolaryngology
Head and Neck
Surgery

Vitamin D

Calcium salt

% elemental
calcium

Other

Carbonate

40

Requires
acid

Phosphate

38

Acetate

25

Citrate

21

Lactate

13

Gluconate

Glubionate

Mechanism
Increases enteric calcium absorption 400%
Stimulates bone resorption in response to PTH

Calcitriol 1,25(OH)2D3
Active and most potent
Added empirically or when oral calcium is inadequate

Better GI
tolerance

Starting dose is .25 mcg/day


Shorter half life  safer in Vitamin D toxicity

Otolaryngology
Head and Neck
Surgery

Walker Harris V, Jan De Beur S . Postoperative hypoparathyroidism. Thyroid. 2009 Sep;19(9):967-73.

Walker Harris V, Jan De Beur S . Postoperative hypoparathyroidism. Thyroid. 2009 Sep;19(9):967-73.

Magnesium

Follow-up

Improves enteric calcium absorption and


Vitamin D production

Endocrinology Colleagues

Replace when hypocalcemia is associated with


hypomagnesemia

Every 1-3 weeks depending on stability

Calcium can inhibit levothyroxine absorption

Calcium and Vitamin D are tapered over several


weeks

IV
Magnesium chloride 4 g IV

In cases of subtotal or total parathyroidectomy

Avoid Magnesium sulfate (MgSO4)

Consideration of autotransplantation of
cryopreserved glands

Sulfate can bind calcium and reduce absorption

PO Magnesium
Diarrhea
Magnesium citrate is often used for bowel prep
Otolaryngology
Head and Neck
Surgery

Otolaryngology
Head and Neck
Surgery
Kronenberg: Williams Textbook of Endocrinology, 11 ed.

Walker Harris V, Jan De Beur S . Postoperative hypoparathyroidism. Thyroid. 2009 Sep;19(9):967-73.

10/23/2010

Cryopreservation

PTH

Success rates of cryopreserved autografts vary


widely

Recombinant PTH administration is being


studied

60% with partial or full function

Unclear what the metabolic risks are

40% with full function

Expensive

Time to reimplant may affect survival

Injected

Variability in freezing techniques

Otolaryngology
Head and Neck
Surgery

No FDA approval for iatrogenic


hypoparathyroidism

Otolaryngology
Head and Neck
Surgery
Cohen MS et al. Long-term functionality of cryopreserved parathyroid autografts: a 13-year prospective analysis. Surgery. 2005

Walker Harris V, Jan De Beur S . Postoperative hypoparathyroidism. Thyroid. 2009 Sep;19(9):967-73.

Summary
Calcium homeostasis is important for normal
function
Post-surgical hypocalcemia is common and
predictable
Post-operative serum calcium and PTH can be
used to risk stratify those at greatest risk
Prophylactic treatment of these individuals will
improve patient care
Do not forget to involve Endocrinology
colleagues
Otolaryngology
Head and Neck
Surgery