Treatment of Suspected Cholelithiasis With Nitroglycerin
Treatment of Suspected Cholelithiasis With Nitroglycerin
ABSTRACT: Sublingual nitroglycerin has been advocated for the treatment of acute pain from
 suspected symptomatic cholelithiasis. There is, however, no clinical studies that validate
 its use. This study is designed to evaluate the efficacy of nitroglycerine in relieving acute
 pain of suspected biliary tract origin.

 Nitroglycerin is a potent smooth muscle relaxant used for biliary tract dilation during ERCP,
 (Chelly, J) and has been recommended for treatment of biliary colic based on anecdotal
 experience and small case reports. Nitroglycerin effect is a result of the nitric oxide
 component of the medication which acts as a smooth muscle relaxant in vascular, bronchial,
 esophageal and biliary smooth muscles. [McGowan(1936), Chelly (1979),Toyoyama (2001)] The
 typical dose of nitroglycerin is 0.4 mg given sublingually in pill form or, more recently, in
 a metered spray form. In a case series reported by Hassel (1993), positive response times
 ranged from 20 to 60 seconds with duration of action of two to twelve hours. Sublingual
 nitroglycerin is most commonly used for treatment of chest pain related to insufficient
 cardiac perfusion. It has also been noted to relieve the pain of esophageal spasms.
 Nitroglycerin has an excellent safety profile if used in patients with adequate pretreatment
 blood pressures. [Newberry (2005), Nitroglycerine (2011), Nitro (2011), Wolters (2009)] This
 study proposes to compare sublingual 0.4 mg doses of nitroglycerin to placebo for the initial
 treatment of acute pain from suspected symptomatic cholelithiasis
General Approach: This study proposes to compare sublingual 0.4 mg doses of nitroglycerin to
 placebo for initial treatment for acute pain from suspected symptomatic cholelithiasis.
 Patients with right upper quadrant abdominal pain of less than 24 hour duration between ages
 18 and 60 years of age will be offered treatment with sublingual nitroglycerin or placebo.
 Patients with obstructive hypertrophic cardiomyopathy, pronounced hypovolemia, STEMI or
 presumed cardiac chest pain, inferior myocardial infarction with right ventricular
 involvement, raised intracranial pressure, cardiac tamponade, and patients taking certain
 drugs for erectile dysfunction (phosphodiesterase inhibitors), pregnancy, or with a known
 allergy to nitroglycerin will be excluded from the study.

 2. Methods: A convenience sample of patients presenting to the Emergency Department will be
 randomized to receive either sublingual 0.4 mg doses of nitroglycerin or placebo. Pain prior
 to and at two minutes and five minutes after medication administration will be assessed using
 a visual analog scale. The medication will be either a 0.4 mg dose of nitroglycerin or a
 placebo. If pain is not completely relieved within five minutes, a second dose will be
 administered after blood pressure assessment. If the pain is not completely relieved after an
 additional two minute and five minute assessment or the pain returns, it will be treated in
 the standard manner at the discretion of the treating Emergency Physician. Ancillary studies
 and other treatments will be at the discretion of the treating physician. The 0.4mg dose of
 nitro has been proven to be a safe and well tolerated dose when administered to our patient
 population in treatment of acute coronary syndrome or suspected angina. Our attending,
 resident, and nursing staff are very familiar with this dose, the potential side effects of
 the medication, and its administration procedure. Therefore, we believe that 0.4mg will be a
 optimal starting dose for enrollees in our study.

 3. Retrovirology Research: None

 4. Investigational Drugs/Devices/Biologics Research: None

 5. Statistical Analysis: Demographic information, patient characteristics, assignment to
 experimental group, and visual analog pain scale data will be entered into a spreadsheet .
 Pain will be recorded per patients at 5 time points: 0, 2, 5, 7, and 10 minutes. Descriptive
 statistics will be presented in tables and graphs. Pain scale results will be analyzed by a
 two-way (2x5) repeated measures analysis of variance with interaction and post hoc multiple
 comparisons. The primary time pair to be tested will be the difference between treatment and
 placebo groups in pain reduction from 0 to 2 minutes. The planned sample size is 62, with 31
 in the placebo group and 31 in the nitro group. The sample size was calculated with the aid
 of Dr Riffenburgh. He agrees with sample size suggested above.

 6. Military Relevance / Operational Use, if any: Sublingual nitroglycerin is a standard AMAL
 list item for independent providers in most field and operational settings. Relief of biliary
 colic can significantly reduce the number of urgent medical evacuations for right upper
 quadrant pain. There is also no mental status degradation with the use of nitroglycerin,
 unlike the opioids commonly used to treat biliary colic.
Inclusion Criteria: Patients with right upper quadrant abdominal pain of less than 24
 hours' duration between ages 18 and 60 years of age will be offered treatment with
 sublingual nitroglycerin or placebo.

 Exclusion Criteria: Patients with obstructive hypertrophic cardiomyopathy, pronounced
 hypovolemia, alcohol use in the last 8 hours, clinical intoxication, STEMI or presumed
 cardiac chest pain, inferior myocardial infarction with right ventricular involvement,
 raised intracranial pressure, cardiac tamponade and patients taking certain drugs for
 erectile dysfunction (phosphodiesterase inhibitors), pregnancy or with a known allergy to
 nitroglycerin will be excluded from the study. Patients unable to give consent will be
 excluded.

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