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“The Science Behind the Art” 
Volume 6 - No. 7 2018 

Anesthesia eJournal - Online
ISSN 2333-2611

Page 33

Safety of Glucagon Use During Endoscopic Retrograde Cholangiopancreatography in 
Patients With Diabetes and Renal Insufficiency: Case Discussion and Review of the 
Literature
Lisa Erlinger, PhD, CRNA1

Terri Monk, MD, MS2

Steven McAfee, MD3

Affiliation:
1 Assistant Professor MidWestern University-St. Louis University, Director of Surgical and Anesthesia Services Wickenburg Community Hospital
2. Professor of Clinical Anesthesiology University of Missouri-Columbia
3. Anesthesiologist University of Missouri-Columbia

Funding/Conflict of Interest Disclosure: 
The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation 
in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or nonfinancial inter-
est (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.
No patient identifying information was used in this case report.

KEYWORDS: Endoscopic retrograde cholangiopancreatography, Glucagon, Diabetes, Renal insufficiency, Hyperkalemia

Abstract
We describe the use of glucagon during endoscopic retrograde cholangiopancreatography (ERCP) resulting in 
significant hyperkalemia. A 45-year-old man with physical classification 3 and type 1 diabetes mellitus, hypertension, 
and chronic kidney disease underwent ERCP with general anesthesia for evaluation of a bile duct stricture. After 
intravenous administration of 0.75 mg glucagon (0.25-mg doses over 1 hour), tall, peaked T waves were noted on the 
electrocardiogram in lead II. Blood was collected and sent to the laboratory for evaluation. The patient’s potassium 
level was 6.6 mEq/L and his glucose concentration was 568 mg/dL (31.5 mmol/L). Calcium chloride 1000 mg was 
administered intravenously. His repeat potassium level was 6.1 mEq/L and his repeat glucose concentration 393 mg/dL 
(21.8 mmol/L). The remainder of the procedure was uneventful and his postoperative potassium level was 5.2 mEq/L.

INTRODUCTION
Endoscopic retrograde cholangiopancreatography (ERCP) is a valuable diagnostic tool in the evaluation of pancreatic-
related diseases such as choledocholithiasis, benign and malignant strictures, and biliary tract disease. ERCP was first 
introduced in the 1960s,1 and its use has steadily grown to approximately 500,000 cases per year in the United States, 
according to the last reported data from 2009.2,3 In the endoscopic portion of the examination, a side-viewing duodenoscope 
is passed through the esophagus and stomach into the second portion of the duodenum. The scope in this position can 
identify the major duodenal papilla and can be used to search for abnormalities. This structure is a projection of the 
hepatopancreatic ampulla (also known as the ampulla of Vader) into the duodenal lumen. The ampulla of Vader is the 
conjunction point of the ventral pancreatic duct and the common bile duct and thus acts as a conduit for drainage of bile 
and pancreatic excretions into the duodenum.4 The ampulla of Vader contains the sphincter of Oddi.5 Cannulation can 
occur in either the common bile duct or the ventral pancreatic duct. Once the duct is cannulated, either a cholangiogram 
(common bile duct) or a pancreatogram (pancreatic duct) is obtained fluoroscopically after injection of radiopaque contrast 
material into the duct.

AEJ
Volume 6 - No. 7 2018



Anesthesia eJournal          www.anesthesiaejournal.com
Volume 6 - No. 7 2018 Page 34

Insulin and glucagon are hormones secreted by islet cells within 
the pancreas. Each counterbalances blood glucose levels to keep 
the body within the normal therapeutic range. One of the many 
functions of insulin is to decrease blood glucose by moving 
glucose into cells. Glucagon is released into the circulation when 
blood glucose is too low, increasing plasma glucose levels. This 
maintains homeostasis in the body and keeps blood glucose 
stable.6

 Glucagon (rDNA origin) for injection (GlucaGen; Novo 
Nordisk A/S) is produced by expression of recombinant DNA in 
a Saccharomyces cerevisiae vector with subsequent purification. 
Glucagon for injection is an anti-hypoglycemic agent and inhibits 
gastrointestinal motility. Hepatic stores of glycogen are necessary 
for glucagon to produce an anti-hypoglycemic effect.7 Glucagon 
induces liver glycogen breakdown, releasing glucose from the liver. 
Blood glucose concentrations rise within 10 minutes of injection, 
and peak concentration is attained approximately 30 minutes 
after injection.

Glucagon also inhibits gastrointestinal motility by relaxation of 
the smooth muscles. The administration of sphincter-relaxing 
agents, like glucagon, enables the endoscopist to extract small, 
common bile duct stones without performing a papillotomy.8 
A papillotomy is performed by cutting the ampulla of Vater to 
widen its outlet to improve bile drainage and allow the passage 
of stones from the common bile duct. Glucagon decreases the 
frequency and amplitude of phasic activity of the sphincter of 
Oddi.8-10 Intravenous glucagon is often used during ERCP to 
inhibit duodenal motility and enhance cannulation. However, 
glucagon can cause significant side effects, including nausea and 
vomiting, hyperglycemia, and hyperkalemia in patients with 
diabetes.11

CASE SUMMARY
A 45-year-old man weighing 61 kg with a body mass index of 22 
presented for an ERCP with cholangiogram. Three months before 
the procedure, he had undergone a laparoscopic cholecystectomy 
with intraoperative cholangiogram. During this initial procedure, 
it was noted that he had a common bile duct stricture. The 
pathology results at that time revealed a high-grade dysplasia of 
the cystic duct stump. He was recommended to undergo further 
evaluation with an ERCP with common bile duct brushings and 
biopsies.

The patient’s medical history included a 30-year history of 
type 1 diabetes mellitus, chronic kidney disease, hypertension, 
hyperlipidemia, and a 20-pack-year smoking history. 
Preoperative laboratory results revealed a creatinine level of 
2.6 mg/dL (230 µmol/L) and a glycated hemoglobin (HbA1c) 
value of 10.4%. He was taking insulin glargine (Lantus), 20 
units subcutaneously at bedtime, and using an insulin lispro 
(Humalog) sliding scale regimen during the day with an average 
use of 40 units daily. His diabetes was poorly controlled with 
daily blood glucose values ranging from 200 to 300 mg/dL 
(11.1-16.6 mmol/L. His preoperative vital signs were blood 
pressure of 130/88 mm Hg and heart rate of 90 beats per minute. 
He had not taken any medications on the day of surgery. His 
preoperative fasting blood glucose concentration was 160 mg/dL 
(8.9 mmol/L) and his potassium level was 4.9 mEq/L.

General anesthesia was induced intravenously with 100 
µg fentanyl, 100 mg lidocaine, and 100 mg propofol. After 
administration of 100 mg succinylcholine, the patient was orally 
intubated and anesthesia was maintained with sevoflurane to 
maintain approximately 1 minimum alveolar concentration. 
The video gastroduodenoscope was advanced to the second 
part of the duodenum and an attempt was made to cannulate 
the common bile duct. Intravenous (IV) glucagon 0.25 mg was 
requested by the gastroenterologist to relax the common bile 
duct. This dose was repeated twice over the next 30 minutes. 
After the third dose, tall, peaked T waves were noted on the 
electrocardiogram (ECG), an acute change from the normal 
ECG at the start of the procedure. The patient’s blood was drawn 
and sent to the laboratory and the findings revealed a potassium 
level of 6.6 mEq/L and a glucose concentration of 568 mg/dL 
(31.5 mmol/L). Calcium chloride 1000 mg IV was administered 
over 10 minutes with improvement in the ECG shown as a 
decrease in amplitude of the peaked T waves. Four puffs of 
nebulized albuterol were also administered via the endotracheal 
tube. Repeat measurements of electrolytes conducted 30 
minutes later showed a potassium level of 6.1 mEq/L and a 
glucose concentration of 393 mg/dL (21.8 mmol/L). Calcium 
chloride 1000 mg IV was administered over 10 minutes with 
improvement in the ECG shown as a decrease in amplitude of 
the peaked T waves. Four puffs of nebulized albuterol were also 
administered via the endotracheal tube. Repeat measurements 
of electrolytes conducted 30 minutes later showed a potassium 
level of 6.1 mEq/L and a glucose concentration of 568 mg/
dL (11.1 mmol/L). The procedure was completed, the patient 
was extubated without incident, and he was monitored in the 
post-anesthesia care unit for 2 hours. Repeat measurements 
of electrolytes showed a potassium level of 5.2 mEq/L and a 
glucose concentration of 505 mg/dL (28.0 mmol/L). The patient 
was transferred to the intensive care department for glucose 
management.

DISCUSSION
Normally, hyperkalemia elicits its own “self-treatment.” This 
is done automatically by the body with endogenous glucose 
and insulin release, insulin-increasing potassium tolerance, and 
endogenous glucagon, which provides enough glucose to prevent 
hypoglycemia.11 This self-regulation allows for administration 
of glucagon in a nondiabetic patient to result in inconsequential 
increases in glucose or potassium. However, as far back as 
1973, a study by Santeusanio et al12 raised the possibility of 
hyperglucagonemia in diabetic ketoacidosis. Santeusanio et al 
had an incidental finding of clinical relevance. They warned 
that patients with diabetic ketoacidosis are at increased risk 
of developing hyperkalemia. This risk is increased if patients 
are administered potassium or encounter a stressful condition 
because endogenous insulin responsiveness is impaired by 
hypercatecholaminemia. They suggested that the risk may be 
excessive unless affected insulin action has been established, 
particularly in patients with kidney disease. Similarly, Massara et 
al13 investigated the role played by glucagon in the regulation of 
plasma potassium. They found low blood insulin and increased 
glucagon could be one of the mechanisms that trigger or magnify 
the hyperkalemia observed in cases of severe stress for patients 
with decompensated diabetes.



Anesthesia eJournal          www.anesthesiaejournal.com
Volume 6 - No. 7 2018 Page 35

Christensen et al14 explored factors that affect the variability in 
heart rate during ERCP. The researchers divided the volunteers 
into 3 groups. Each group received an administration of 
butylscopolamine, glucagon, or saline, and the researchers looked 
for myocardial ischemia and changes in the variability of heart 
rate. Two patients in the butylscopolamine-free group developed 
ischemia, resulting in unexplained pathophysiologic changes.14 

The ST segment depressions in the Christensen et al study lasted 
226 s and 550 s, respectively. Could this be the result of transient 
hyperkalemia from glucagon? No further information was given 
concerning patient histories to make any conclusions for practice.

Tall, peaked T waves are findings of concern in the perioperative 
setting, particularly, as in this case, when they represent a 
change from the patient’s baseline. The differential diagnosis 
of prominent T waves can include hyperkalemia, myocardial 
ischemia, left ventricular hypertrophy, benign early repolarization, 
bundle branch block, pericarditis, and normal variant, especially 
in the young.15

Hyperkalemia or myocardial ischemia was most likely the cause 
in this case, because the T wave elevation developed as an acute 
change from the start of the procedure. The laboratory evaluation 
confirmed that hyperkalemia was the diagnosis. The treatment 
of acute hyperkalemia included administration of calcium 
chloride IV to stabilize the cardiac membrane from potentially 
fatal arrhythmias. The recommended dose is 10 to 20 mL of a 
10% calcium chloride solution and a ß-adrenergic agonist such 
as nebulized albuterol to redistribute extracellular potassium 
into the cells. A sodium bicarbonate–glucose-insulin mixture 
could also have been used. Sodium bicarbonate 0.5-1.0 mEq/
kg IV shifted potassium intracellularly while the glucose-insulin 
infusion (50 mL of 50% glucose plus 10 units regular insulin) 
produced a sustained transfer of extracellular potassium into 

the cells. Therapeutic agents could also have been administered 
to lower the total body potassium. Polystyrene compounds 
(Kayexalate) or loop-diuretics both increase potassium excretion 
via gastrointestinal and renal systems, respectively.

This case demonstrates the importance of considering alternative 
means of duodenal antiperistalsis and sphincter of Oddi 
relaxation to allow for ampullar cannulation in patients with 
diabetes and/or chronic kidney disease undergoing ERCP. One 
such agent is L-hyoscyamine, an anti-cholinergic, anti-muscarinic 
alkaloid that is frequently administered via the sublingual 
route. A review of the literature did not support widespread use 
of L-hyoscyamine. L-Hyoscyamine is associated with peri-
procedural adverse effects including nausea and vomiting and 
has not been shown to decrease the amount of glucagon patients 
receive.11,16 Perhaps a better strategy would be to minimize the 
use of glucagon in patients with diabetes at elevated risk for 
hyperkalemia.

CONCLUSION
This is the first report of acute hyperkalemia during ERCP. 
Although rare, this complication can be life-threatening if not 
recognized and immediately treated. In nondiabetic patients, 
glucagon administration causes a modest increase in plasma 
potassium levels, but these effects are magnified in patients with 
diabetes, especially in individuals who are insulin deficient or 
have a history of uncontrolled diabetes. The anesthesia provider 
should be aware of the possibility of hyperkalemia during ERCP 
and its effects on the myocardium. It is important to formulate 
a suitable approach to the management of hyperkalemia during 
ERCP. It may be prudent to check serum potassium and blood 
glucose in all patients with diabetes, especially those with chronic 
kidney disease.



Anesthesia eJournal          www.anesthesiaejournal.com
Volume 6 - No. 7 2018 Page 36

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