**4. Treatment of severe hypocalcemia with our algorithm**

Cozzolino et al. [27, 28] proposed a dose corresponding to the rate of 1–2 mg/kg/h for i.v. Ca gluconate, which could be increased or decreased by 25–50% from the initial value. Loke et al. [17] developed a titration regimen in which a 10% Ca gluconate infusion was started at 4.5 mL/h when serum Ca levels were < 8 mg/dL and then increased to 6.5 mL/h and finally to 9.5 mL/h if Ca levels continually declined. The algorithms they proposed were too complicated for clinical applications, and therefore, we modified it into our clinical algorithm (**Figure 2**). We adopted the clinical algorithm developed by Cozzolino et al. [28], with some modifications.

**Figure 2.**

*Mineral Deficiencies - Electrolyte Disturbances, Genes, Diet and Disease Interface*

**Mild hypocalcemia**

Ca [7.9–9.9 mg/dL] 7.3 (6.8–7.9) 7.0 (6.6–7.7) 0.013 P [2.4–4.7 mg/dL] 4.0 (3.2–5.1) 4.1 (3.2–4.9) 0.958 Alk-ptase [28–94 IU/L] 192 (113–343) 349 (191–636) <0.001 iPTH [14–72 ng/mL] 8.8 (2.9–16.4) 10.1 (2.8–20.6) 0.343

**[Normal ranges] Group A (N = 247)**

to normal levels at 3 months post-operation (**Table 4**). Before patients were discharged in our series, the mean Alk-ptase level was still higher in Group B than in Group A showing that oral Ca carbonate and calcitriol should be continually administered for 2 weeks to 3 months, according to serum Ca levels [15].

*Risk factors of severe hypocalcemia after total parathyroidectomy plus auto transplantation.*

0.003 0.010

Preoperatively, high iPTH levels were a clear indicator of the severity of renal hyperparathyroidism and bone disease. Preoperatively, high iPTH levels increased both bone formation and bone resorption; after parathyroidectomy, bone resorption would decrease and bone formation would increase; thus, severe hypocalcemia could

**Risk factors unit Coefficient p Odds ratio 95% CI** Age 1year −0.045 =0.001 0.956 0.931–0.982 Ca 1 mg/dL −0.520 0.007 0.595 0.409–0.866

*Serum calcium (Ca), phosphate (P), alkaline phosphatase (Alk-ptase) and intact parathyroid hormone (iPTH) levels at the day of discharge. Comparison between mild (Group A) and severe (Group B)* 

> <0.001 0.016

1.003 1.010

**Group B (N = 75) Severe hypocalcemia**

> 1.001–1.004 1.002–1.018

**p**

We found that the total weight of the removed parathyroid glands was more in Group B than in Group A, as was the operation time. The total weight of parathyroid glands and the operation time contributed to severe hypocalcemia, might be due to advance disease and extensive dissection during surgery, but were rarely

Multi-variant binary logistic regression test showed that young age, low preoperative Ca levels, high preoperative Alk-ptase levels, and long operation time were independent risk factors for severe hypocalcemia, with associated odds ratio of 0.956, 0.595, 1.003, and 1.010, respectively (*p* = 0.001, *p* = 0.007, *p* < 0.001, and

In our study, Ca levels were negatively correlated with P levels (*r* = −0.255, *p* < 0.001), and Alk-ptase levels were positively correlated with iPTH levels (*r* = 0.449, *p* < 0.001); therefore, preoperative Ca and Alk-ptase levels were finally identified as independent risk factors for severe hypocalcemia combined with

**104**

develop after surgery [14, 22, 24].

Alk-ptase 1 IU/L Operation time 1 min

*hypocalcemia groups.*

*Using Mann-Whitney U test.*

*All data = median (interquarter range) (IQR).*

*Ca = calcium levels.*

**Table 4.**

**Table 3.**

*Using binary logistic regression test.*

*Alk-ptase = alkaline phosphatase.*

reported before [20, 25, 26].

*p* = 0.016, respectively) (**Table 4**).

young age and long operation time.

*The clinical algorithm for the treatment of hypocalcemia after total parathyroidectomy plus autotransplantation for secondary hyperparathyroidism.*

At 18 h post-operation, Ca, P, and iPTH levels were checked to ensure that the operation had been successful and the levels of iPTH were < 72 pg/mL and P levels were above the normal lower limit (2.4 mg/dL).

If serum Ca levels were > 7.6 mg/dL at 18 h post-operation, oral Ca carbonate 2–4 g/day and calcitriol 0.5–1 μg/day were administered; Ca levels were checked on alternate days.

If serum Ca levels were ≤7.6 mg/dL and >6.5 mg/dL at 18 h post-operation, i.v. Ca gluconate (10%) 4–6 g in 75 mL of 5% glucose in water (D5W) or normal saline was administered for 24 h, concomitant with oral Ca carbonate 4–6 g/day and calcitriol 2 μg/day; Ca levels were checked daily.

If serum Ca levels were ≤6.5 mg/dL at 18 h post-operation, i.v. Ca gluconate 8 g in 150 mL D5W was administered for 24 h, concomitant with oral Ca carbonate 6–8 g/day and calcitriol 4 μg/day; Ca levels were checked daily except Ca levels <6.0 mg/dL. In that situation, Ca levels were checked every 12 h until they reached levels ≥6.0 mg/dL.

If patients had symptoms and signs of hypocalcemia, such as paresthesia of the mouth and extremities, muscle spasms, Chvostek's sign, Trousseau's sign, seizure, tetany, EKG abnormalities, arrhythmia, and hypotension, Ca levels were checked immediately and i.v. Ca gluconate 2 g in 15 mL D5W was administered in 15 min; Ca levels were then checked as usual and treated accordingly (**Figure 2**).

At 5–7 days post-operation, if patients' Ca levels were > 7.6 mg/dL, they were discharged with oral calcium carbonate 2–4 g/day and calcitriol 0.5–2 μg/day.

If Ca levels were stable and ≥ 6.5 mg/dL, they were discharged with oral Ca carbonate 6–8 g/day and calcitriol 4 μg/day. If Ca levels were < 6.5 mg/dL, they were kept in hospitalization and treated as per the clinical algorithm (**Figure 2**).

Following the clinical algorithm post-operatively, we administrate i.v. Ca gluconate 4–6 g in 75 mL D5W or normal saline in 24 h for patients with Ca levels <7.6 mg/dL, Ca gluconate 8 g/day in 150 mL D5W or normal saline in 24 h for patients with Ca levels <6.5 mg/dL, and i.v. Ca gluconate 2 g/15 mL D5W or normal saline in 15 min for patients with symptoms and signs of hypocalcemia. More concentrated solution for continuous infusion should be infused via central line [29]. Either 10% Ca gluconate (40 mg of elemental calcium per 10 mL) or 10% Ca chloride (270 mg of elemental calcium per 10 mL) can be used to prepare the infusion solution. Ca gluconate is preferred because it causes less tissue necrosis if extravasated [30]. The amount of i.v. Ca gluconate is adjusted by serum Ca levels and duration (days), neither by patients' body weight nor i.v. speed.

The K/DOQI guidelines and others suggest that serum Ca levels should be measured every 4–6 h post-operation [27, 31], but according to our experience and some other authors [28], this is not necessary except when Ca levels are <6.0 mg/dL. In such cases, we measured Ca levels every 12 h, until they were stable and reached ≥6.0 mg/dL.
