Treatment of Suspected Cholelithiasis With Nitroglycerin
| Status: | Recruiting |
|---|---|
| Conditions: | Gastrointestinal |
| Therapuetic Areas: | Gastroenterology |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 10/1/2017 |
| Start Date: | October 2014 |
| End Date: | March 2019 |
| Contact: | steven j portouw, MD |
| Email: | steven.portouw@med.navy.mil |
| Phone: | 619-532-8274 |
Treatment of Suspected Cholelithiasis With Nitroglycerin: a Randomized, Prospective Double-blind Trial
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
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.
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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