Case Report
A NEWLY DEVISED VASOPRESSIN DRIP PROTOCOL
IN THE MANAGEMENT OF CHRONIC CENTRAL DIABETES
INSIPIDUS DURING FACIAL TRANSPLANTATION SURGERY
Khawla F. Ali, MD1; Vicente T. San Martin, MD1; Lea El-Hage, MD1;
Christine Ahrens, PharmD, RPh2; Kevin M. Pantalone, DO1; Robert S. Zimmerman, MD1;
Laurence Kennedy, MD1; Pratibha Rao, MD1
ABSTRACT
Objective: Titration of desmopressin can be challeng-
ing during complex, lengthy surgical procedures in patients
with chronic central diabetes insipidus (DI). Arginine vaso-
pressin (AVP) may be the preferred treatment modality in
these settings. No data currently exist on the use of AVP
during lengthy operations.
Methods: We report a novel AVP infusion protocol for
the management of chronic DI during a 27-hour total facial
transplantation surgery.
Results: A 21-year-old woman was admitted for a total
facial transplantation surgery. Her medical history was
significant for severe facial injuries and panhypopituita-
rism, both secondary to a ballistic trauma sustained 3 years
prior. For the management of her chronic central DI during
the complex surgery, a unique AVP infusion protocol was
developed. Intraoperatively, the infusion was adjusted
hourly following an internally developed algorithm with
pre-specified goal parameters for urine output (50 to 200
mL/hour) and serum sodium levels (136 to 144 mmol/L;
reference range: 136 to 144 mmol/L). The short half-life
of AVP provided ease of dose titration. Under this proto-
col, the patient’s hemodynamic values and serum sodium
levels remained stable throughout the 27-hour transplanta-
tion surgery.
Submitted for publication April 3, 2018
Accepted for publication June 11, 2018
From the Departments of 1Endocrinology, Diabetes and Metabolism, and
2Pharmacy, Cleveland Clinic, Cleveland, Ohio.
Address correspondence to Dr. Pratibha Rao, Department of Endocrinology,
Diabetes and Metabolism, Cleveland Clinic Foundation, 9500 Euclid Avenue
/ F-20, Cleveland, Ohio 44195.
E-mail: raop@ccf.org.
DOI:10.4158/ACCR- 2018-0153
To purchase reprints of this article, please visit: www.aace.com/reprints.
Copyright © 2018 AACE.
Copyright © 2018 AACE AACE CLINICAL CASE REPORTS Vol 4 No. 6 November/December 2018 e497
This is an Open Access article under the CC-BY-NC-ND license.
Conclusion: We describe the successful use of a novel
AVP infusion protocol for the management of DI during a
27-hour facial transplantation surgery. This protocol may
also be effective in managing other patients with chronic
central DI during lengthy intraoperative periods. (AACE
Clinical Case Rep. 2018;4:e497-e500)
Abbreviations:
AVP = arginine vasopressin; DDAVP = 1-deamino-
8-D-arginine vasopressin; DI = diabetes insipidus
INTRODUCTION
Central diabetes insipidus (DI) is a clinical syndrome
characterized by impairment of the hypothalamic-pituitary
axis’ ability to produce, transfer, or restore arginine vaso-
pressin (AVP), also known as antidiuretic hormone (1,2).
In chronic central DI, desmopressin (1-deamino-8-D-ar-
ginine vasopressin; DDAVP) is the preferred treatment
modality given its ease of administration, tolerability, and
favorable safety profile (3). However, from our experi-
ence, the titration of DDAVP could be very challenging
during prolonged (>10-hour) intraoperative periods, due to
its relatively long duration of action (4). Complex surgi-
cal procedures involve significant hemodynamic shifts
making DDAVP an unreliable predictor of intraoperative
serum sodium levels. In this sense, AVP yields a more
favorable pharmacodynamics profile; it has a shorter half-
life estimated at 10 minutes (5), and consequently, it can be
promptly titrated if needed.
Continuous intravenous infusion of dilute AVP has
been utilized to manage acute central DI in postoperative
neurosurgical settings (6); however, no data currently exist
on the use of AVP for the management of chronic central
DI during surgical procedures (7). Herein, we report the
development and implementation of a newly devised AVP
e498 Operative Vasopressin in Chronic DI, AACE Clinical Case Rep. 2018;4(No. 6)
protocol for the management of a patient with chronic,
central DI during a 27-hour facial transplantation surgery.
CASE REPORT
A 21-year-old woman was admitted in 2017 for a
total facial transplantation surgery. Her medical history
was significant for severe facial injuries and panhypopi-
tuitarism, both secondary to a ballistic penetrating trauma
sustained 3 years prior. Her home medication regimen
included levothyroxine (125 μg orally daily) for second-
ary hypothyroidism and DDAVP (0.5 mg orally daily, in 3
divided doses of 0.2 mg at 9:00 am, 0.1 mg at 1:00 pm, and
0.2 mg at bedtime) for central DI. She had been on hydro-
cortisone (total daily dose of 15 mg) for secondary adrenal
insufficiency, but this had been successfully tapered off
several months prior to transplantation based on normal
cortisol response to cosyntropin stimulation. Her baseline
serum cortisol measured 7.2 μg/dL (reference range: 3.4
to 26.9 μg/dL). Thirty and 60 minutes post-administration
of 0.25 mg of intramuscular cosyntropin, serum cortisol
levels were 16.5 and 23.7 μg/dL, respectively. The patient
had also developed secondary hypothalamic amenorrhea
as a result of the earlier trauma. She weighed 70 kg at the
time of surgery.
The outpatient management of her central DI had been
difficult, mainly due to associated adipsia. Her thirst mech-
anism was severely impaired, indicating concomitant post-
traumatic hypothalamic osmoreceptor dysfunction. Her
inpatient management, especially during past admissions
for surgical procedures, had also been very challenging due
to occurrences of significant sodium derangements despite
minimal fluid interventions.
In one instance, the patient was electively admitted
for a brief plastic surgical procedure of only 1.5 hours in
duration. On the morning of that surgery, she was adminis-
tered her home dose of desmopressin of 0.2 mg orally. She
received 1.5 L of Ringer’s lactate solution during the surgi-
cal intervention and, postoperatively, she was started on a
5% dextrose and 0.45% sodium chloride solution at a rate
of 75 mL/hour and was given her evening dose of DDAVP
of 0.2 mg orally. A few hours later, the patient sustained
a witnessed tonic-clonic seizure and had to be trans-
ferred to the intensive care unit. The cause of the seizure
was deemed hyponatremia; her serum sodium level had
dropped from a presurgical level of 142 mmol/L (reference
range: 136 to 144 mmol/L) to 122 mmol/L at the time of
seizure activity. The drop in serum sodium was attributed
to the volume (despite its relatively miniscule amount) and
the type of fluids administered (dextrose-containing fluid).
The patient had a subsequent long recovery period in the
intensive care unit but was discharged in stable condition
with good neurological recovery.
Given the challenges encountered during the patient’s
previous hospital stays as demonstrated above, a unique
Copyright © 2018 AACE
vasopressin protocol was developed to manage her DI
during the complex and lengthy facial transplantation
surgery. Her serum sodium level on the night prior to the
surgery was within normal limits (138 mmol/L) and she
received her bedtime dose of DDAVP 0.2 mg at 9:00 pm.
On the morning of the surgery, she received her regu-
lar dose of levothyroxine 125 μg at 6:00 am. The organ
retrieval process had started earlier that day and she was
scheduled to enter the operating room at 1:00 pm. She was
given her usual dose of DDAVP of 0.2 mg at 9:00 am, 4
hours before the surgery. At 1:00 pm, when she was due for
her next dose of DDAVP, an infusion of AVP was started at
a rate of 0.02 U/minute.
Intraoperatively, the infusion was titrated hourly based
on the devised algorithm (Table 1). The patient’s serum
sodium levels had no significant variations throughout the
27-hour long surgery. Figure 1 illustrates sodium levels,
hourly urine output rates, and hourly AVP infusion rates
during the facial transplantation surgery. Her hemody-
namic values (blood pressure and heart rate) were stable
throughout. For intravenous fluid replacement, the patient
received a continuous infusion of Plasma-Lyte, an isotonic
solution (osmolality of 294 mOsmol/L, normal physiologic
serum osmolality range: 280 to 310 mOsmol/L), at a rate of
350 mL/hour.
At the end of the surgical procedure, she was given 1
DDAVP dose of 0.1 mg through her feeding tube. Bridging
with AVP infusion was done for 2 hours post-administra-
tion of enteral DDAVP and the infusion was then discon-
tinued. Thereafter, the enteral doses of DDAVP were deter-
mined based on her urine output and serum sodium levels.
During the 48 hours that followed the transplantation, the
patient’s serum sodium levels remained stable, with mini-
mal variations ranging from 135 to 140 mmol/L.
DISCUSSION
As surgical techniques continue to evolve, complex
procedures are now available for a larger cohort of patients.
The management of fluid shifts during these complex and
prolonged surgical interventions continues to present with
challenges. Patients with chronic DI can develop intraop-
erative sodium derangements even when receiving their
usual doses of DDAVP. The ability of DDAVP to rapid-
ly counteract intraoperative volume changes is limited,
mainly due to its relatively long duration of action (5).
In this regard, although the vast majority of DI patients
are currently managed intraoperatively with DDAVP and
intravenous fluid titration, we believe AVP constitutes a
better option in lengthy operative settings for patients with
a proven record of unusual and difficult-to-control DI in
past surgical operations.
No clinical data exist regarding an adequate conver-
sion of DDAVP into AVP, so the determination of an appro-
priate infusion rate of AVP was challenging. For patients
Copyright © 2018 AACE Operative Vasopressin in Chronic DI, AACE Clinical Case Rep. 2018;4(No. 6) e499

Table 1
Vasopressin Infusion Algorithm
• Inject 20 units of vasopressin in D5W 100-mL bag (20% concentration bag)
• Initiate vasopressin infusion at 0.02 U/minute when patient’s next dose of DDAVP is scheduled
immediately prior to surgery
• Titrate vasopressin infusion (by 0.001-0.01 U/minute) based on the following*:
- Increase rate of infusion if UOP >200 mL/hr (deviation: if sodium reaches 136 mmol/L or lower, do not
increase rate of infusion)
- Decrease rate of infusion if UOP <50 mL/hour
- Increase or decrease rate of infusion if ≥3 mmol/L change in sodium per hour for 2 hours consecutively
- Increase rate of infusion if sodium reaches >145 mmol/L
- Decrease rate of infusion if sodium reaches <136 mmol/L
• Vasopressin takes its effects 30 minutes after dose change; if goal UOP or sodium is not achieved in 60
minutes, titrate infusion further
• Obtain hourly serum sodium levels (through point-of-care arterial blood gas testing)
• Obtain hourly inputs and outputs
• Goal sodium is 136-144 mmol/L (sodium reference range: 136-144 mmol/L)
• Goal UOP is 50-200 mL/hour
Abbreviations: D5W = dextrose 5% water; DDAVP = 1-deamino-8-D-arginine vasopressin; UOP = urine output.
*Degree of change in infusion rate is at the discretion of the anesthesiologist.

Fig. 1. Sodium levels, hourly urine output rates, and hourly arginine vasopressin infusion rates during the facial transplantation surgery. The values outside
of the circles represent hourly arginine vasopressin infusion rates (U/minute). The values inside of the circles represent UOP in mL/hour. Dark grey circles
represent UOP >200 mL/hour, light grey circles represent UOP between 50 to 200 mL/hour, and white circles represent UOP <50 mL/hour. Abbreviation:
UOP = urine output.

who are already receiving AVP, the current guidelines
recommend converting the intramuscular or subcutaneous
requirements into a continuous intravenous infusion rate
(8). Since our patient was not being managed with AVP
prior to her surgery, we decided to use the recommended
total daily dose of AVP to estimate an appropriate start-
ing rate for the infusion. The recommended starting dose
for AVP in adults with acute DI ranges from 10 to 40 U/
day, which is equivalent to 0.007 to 0.03 U/minute (8). We
selected a starting rate of 0.02 U/minute given our patient’s
high baseline DDAVP requirements prior to surgery. A
previous report had used a constant rate of 0.04 U/minute
(2.5 U/hour) for the management of a patient with posttrau-
matic acute DI (9). From our clinical experience, we felt
this initial dose would have been too high for this patient,
given that AVP requirements are usually observed to be
lower in patients with chronic versus acute DI.
In contrast, data from the pediatric literature suggest a
starting dose of 0.5 mU/kg/hour (10,11). This is equivalent
to 0.0006 U/minute for a 70-kg subject. Certainly, the latter
dose would have been too low for this patient. Additionally,
due to likely residual effects of oral DDAVP administered
the morning of surgery, we have seen lower AVP rates in
the first 10 hours of surgery compared to the remainder
of surgery.
Another key element in the development of our AVP
protocol was the use of a low-concentration solution of
AVP to allow for the slowest possible rate of infusion
(0.001 U/minute). We also allowed for a higher urine
output threshold (200 mL/hour) for adjustment of AVP
e500 Operative Vasopressin in Chronic DI, AACE Clinical Case Rep. 2018;4(No. 6)
infusion rate, to account for the high volume of crystal-
loids administered during prolonged surgical interventions.
Additionally, if urine output exceeded 200 mL/hour but
serum sodium measured 136 mmol/L or lower, the rate of
AVP infusion would not be increased in order to avoid free
water toxicity and further lowering of sodium levels. Once
serum sodium rises to >136 mmol/L, the AVP rate would
then be increased as outlined in the algorithm (Table 1).
Recent reports published by Bohn et al (12) indicated
the use of a tonicity balance in understanding the basis for
changes in sodium levels and proposing goals for natremia
therapy in polyuric settings. The tonicity balance formula
takes into account both intravenous gains and renal losses
of electrolytes (sodium and potassium) and fluids to predict
changes in sodium and direct goals of therapy. The formula
assumes that non-renal losses are small and are therefore
not accounted for in the calculation (12). Due to the nature
of facial transplantation surgeries where large surface areas
are exposed to air for prolonged periods of time leading to
significant insensible water losses, a tonicity balance could
not be utilized for this case. However, it remains a good
consideration for future surgical cases with less insensible
water losses.
CONCLUSION
We demonstrated the successful use of a novel AVP
infusion protocol for the management of chronic DI in a
27-hour facial transplantation surgery. This protocol may
also be effective in managing other patients with chronic,
unusual, and difficult-to-control DI during lengthy intraop-
erative periods.
DISCLOSURE
The authors have no multiplicity of interest to disclose.
Copyright © 2018 AACE
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