Running Head: PICO: MEPERIDINE VERSUS MORPHINE 1

Is Meperidine or Morphine Better for Treating Pain Related to Cholecystitis and Pancreatitis?
Alyssa Breda
NURS 612.01: Care of the Adult with Acute Illness II
Dr. Susan Fetzer
University of New Hampshire
5/6/2014








MEPERIDINE VERSUS MORPHINE 2
Abstract
This paper will give a brief overview about the function of the gallbladder and pancreas, as
well as the background of cholecystitis and pancreatitis. It will then review and discuss research
findings to determine whether morphine or meperidine is more effective in treating the pain
related to these conditions.



















MEPERIDINE VERSUS MORPHINE 3
Background and Rationale
Cholecystitis and pancreatitis are both conditions that interfere with the digestive process,
since they inhibit normal functioning of the gallbladder and pancreas. The gallbladders function
is to store bile, which is made in the liver. The purpose of bile is to breakdown fat. Therefore,
when fat is ingested, the gallbladder releases the bile, which then travels through the cystic duct
and common bile duct to the sphincter of Oddi, which allows it to pass into the duodenum of the
small intestine. In cholecystitis, there is inflammation of the gallbladder wall, often caused by
gallstones. These gallstones usually form in the cystic duct or common bile duct, causing back
up of bile into the gallbladder. This results in irritation and inflammation of the gallbladder wall
(Sommer et al.).
The function of the pancreas in terms of digestion is to secrete enzymes that break down
carbohydrates, proteins, and fats. These enzymes are created by the pancreas and released during
digestion, at which point they travel from the pancreas through the Sphincter of Oddi and into
the duodenum of the small intestine. In pancreatitis, however, the digestive enzymes are
prematurely activated, causing auto-digestion of the pancreas (Sommer et al.). The mechanism of
action for this condition is unknown, however it is speculated that there may be a dysfunction of
the sphincter of Oddi. If this is the case, the sphincter would not open to allow the passage of
enzyme into the small intestine, causing back up of enzymes and auto-digestion of the pancreas
(Sphincter of Oddi Dysfunction).
Cholecystitis is characterized by sharp pain located in the right upper quadrant. This has the
potential to radiate, often to the right shoulder. There is also severe pain when the client inhales
deeply, as well as when the client eats a high-fat meal, also referred to as biliary colic. Those
who suffer from pancreatitis also have pain in the abdomen, located in the middle-upper region.
This worsens upon eating, drinking alcohol, or consuming foods that are high in fat. This pain is
MEPERIDINE VERSUS MORPHINE 4
very debilitating for these patients, and it is important for the health care team to decide how to
best alleviate this pain in order to increase quality of life (Sommer et al.).
In this paper, both morphine and meperidine will be discussed in terms of their effectiveness
to treat pain related to these conditions. There is much debate about which of these opioid
analgesics is more effective in treating the pain related to both cholecystitis and pancreatitis.
Many believe that meperidine is more beneficial, and doesn't irritate the sphincter of Oddi to the
extent of which morphine does. However, looking at research and recent studies will provide
answers as to which is most effective in evidence-based treatment.
Search Methods
Databases that were searched include CINAHL, EBSCO, UpToDate, PubMed, and
ScienceDirect. Google search engine was also used to search specific references cited in articles
found on the databases, as well as basic definitions and pathophysiology of the conditions. When
a database was found through Google, research was conducted through the database via the UNH
Library online. Key words used to search for the articles were Morphine cholecystitis,
Cholecystitis pain treatment, Meperidine versus Morphine, Pancreatitis and cholecystitis
pain, Sphincter of Oddi morphine, Sphincter of Oddi meperidine, and meperidine for pain
in cholecystitis. These searches eventually led to articles that were relevant and pertinent to the
research topic. Some articles were accessed through the references of articles found directly
through the databases. Limits that were applied include English Language, Linked Full Text, and
Abstract available. The number of citations identified for this article is a total of nine. The
inclusion criteria included articles and research studies that compared morphine and meperidine
related to cholecystitis and/or pancreatitis, and for treatment of pain with sphincter of Oddi
dysfunction. Articles were also chosen that addressed the affects of these opioids on the body in
relation to the sphincter of Oddi and in relation to the conditions specifically. Any articles that
MEPERIDINE VERSUS MORPHINE 5
discussed these drugs in relation to each other or the relevant digestive conditions were taken
into consideration. Articles that were excluded were ones that did not directly address the topic,
that were outdated, and that did not yield any significant results.
Critical Appraisal of the Evidence
The first research study is titled A cross-over comparison of the effect of morphine, pethidine,
pentazocine, and phenazocine on biliary pressure. Although this study was published in 1971, it
still provides a strong base for the current argument that meperidine should be used over
morphine in the treatment of biliary and pancreatic pain. This study compares the effects of
morphine, meperidine, pentazocine, and phenazocine on the pressure of the biliary duct leading
to the sphincter of Oddi. For the purpose of this paper, however, only pethidine (meperidine) and
morphine will be the focus (Economou et al.).
In the study, 31 patient underwent surgery and had T tubes inserted to measure biliary
pressure. According to the study, Bile pressure was measured directly in centimeters of bile
through a transparent plastic tube attached to the shortened 12F 'T' tube (Economou et al.). Each
patients resting pressure was measured with him or her lying flat with one pillow. All patients
were measured at 18 cm or less of bile above the duct. Out of these 31 patients, 11 were given a
dose of 30-45 mg of morphine injected intramuscularly. Another 11 patients were given 30-45
mg of pethidine intramuscularly. Pressures were measure at 30, 60, and 120-minute intervals
after medication administration. The morphine group experienced an increase of 7 cm at 30
minutes, 8.4 cm at 60 minutes, and 5.9 cm at 120 minutes. In the pethidine group, patients
experienced an increase of 3.2 cm at 30 minutes, 3.9 cm at 60 minutes, and 3.7 cm at 120
minutes. Thus, this study concludes that the pressure within the biliary duct is increased
significantly more by morphine than it is by that of pethidine. Weaknesses of this study however,
are that it is an older study, and used a measurement system that did not use any official
MEPERIDINE VERSUS MORPHINE 6
recording devices that would reveal the actual biliary pressure. This may allow for some error in
the studys results. Another weakness was that these tests were done a couple of days after the
operation, which could have caused an increase in biliary pressure as well, possibly skewing the
results (Economou et al.).
The findings regarding the increase of biliary pressure related to morphine was also confirmed
by another study, entitled, Effects of morphine on the human sphincter of Oddi. This study is also
rather dated, and was published in 1988. However it, too, explains why the medical field favors
meperidine over morphine in terms of pressure within the biliary ducts. The study examines 19
patients, ages 25-73, without evidence of biliary or pancreatic diseases. The patients underwent
an endoscopic retrograde cholangiopancreatography (ERCP) to measure the pressures in the
sphincter of Oddi via a manometeric catheter to determine if morphine increases pressure or
causes spasms. Each patient was given 4 doses of morphine, each at five-minute intervals. The
doses consisted of 2.5, 2.5, 5, and 10 g/kg intravenously. Before the procedures, the patients
were given 10-15 mg of Diazepam for sedation, which reportedly does not affect the sphincter of
Oddi. The study showed that the doses of morphine cause significant increases in both the phasic
wave pressures and basal pressures of the sphincter of Oddi, as indicated by multiple graphs
throughout the article that show the increase of pressures that occur after the doses of morphine
were administered. Naloxone was also administered to reverse the morphine, but when the
pressures only decreased slightly, it was concluded that other receptors, in addition to the mu
receptors, were being influenced by morphine in the sphincter of Oddi. In conclusion, this study
shows that morphine not only causes increased pressure in the sphincter of Oddi, but also causes
spasms, as indicated by the increase in basal pressure. Weaknesses to this study include the fact
that morphine is not being compared to meperidine, making it hard to determine the effect of one
MEPERIDINE VERSUS MORPHINE 7
versus the other. Another weakness is that the patients were sedated, which may or may not have
some underlying effect of the results. The participants of the study also did not have biliary or
pancreatic disease or pain, which makes it hard to relate the increase in pressure to an increase in
pain. The study also did not give exact measurements of the differences in pressure before and
after morphine administration, although the graphs do provide rough estimates of these values.
Thus, this study shows that morphine causes an increase in pressure of the sphincter of Oddi.
This, however, does not directly correlate to an increase in pain for the participant (Helm et al.).
The third study, published in 1996, provides a comparison for the effects of morphine on
sphincter of Oddi pressures. In this study, it is meperidine being examined in regards to its
effects on pressure within the sphincter of Oddi. Forty-seven patients with pancreaticobiliary
pain underwent sphincter of Oddi manometry, just as the participants in the previous study. The
participants were sedated with diazepam, and meperidine was given intravenously in doses
ranging from 45-75 mg, with an average of 56 mg. The results showed that meperidine actually
lowered phasic pressure in 72.2% of participants, but increased the phasic wave frequency in
77.8% of the participants. These results differ from the results found in the first study, which
concluded that meperidine raised the pressures in the biliary ducts. This poses a predicament,
since these studies are contradictory in their final results for meperidines effect on the pressure
in biliary ducts and the sphincter of Oddi. A weakness of this study includes the fact that the
participants were sedated, and as stated before, this may have produced some type of error in the
results. Also, since they were sedated, the participants could not report if any pain relief was
experienced. This means the study was limited to examining the pressure in the sphincter instead
of how the pressure related to pain levels. This is also limiting because, like the previous two
MEPERIDINE VERSUS MORPHINE 8
studies, this article is somewhat older, and therefore it may have lower credibility than newer,
more recent studies (Sherman et al.).
These older research articles examine the effect of meperidine and morphine internally on the
sphincter of Oddi. Two of the studies were performed when the patients were sedated, and the
other did not mention the effect of the medications on pain. However, since these studies found
how the drug influences pressure, it is presumed that an increase in pressure would lead to an
increase in irritation in both the gallbladder and pancreas if disease were present. This would be
due to the back up of either bile or pancreatic enzymes due to increased pressure within the
sphincter of Oddi. This however, is not specified. Due to this, newer research is claiming that
there is no scientific evidence to say that meperidine is superior to morphine in treatment of
biliary or pancreatic pain.
According to one article published in 2004, the 'pethidine is better than morphine sulphate'
debate is based on a common misconception that pethidine does not affect the sphincter of Oddi.
In fact, like all opioids it can increase smooth muscle tone and so reduce biliary and pancreatic
secretions and so increase bile duct pressure There is no research evidence for using pethidine
over morphine in patients with pancreatitis, (Parker). Many other recent studies claim this to be
true as well. S. S. Vege also states, there are no clinical studies to suggest that morphine can
aggravate or cause pancreatitis or cholecystitis. In addition, meperidine has a short half-life and
repeated doses can lead to accumulation of the metabolite normeperidine that causes
neuromuscular side effects and, rarely, seizures, (Vege). Lastly, a third article states this as well,
saying Traditionally, pethidine was the drug of choice as it was believed that this caused less
spasm in the Sphincter of Oddi than morphine. However, there are no definitive studies that
support this view, (Sargent).
MEPERIDINE VERSUS MORPHINE 9
Not only do most recent research articles claim that there is insufficient research-based
evidence to suggest that meperidine is superior to morphine in the treatment of cholecystitis and
pancreatitis, but most recent research also agrees that morphine is in fact more safe to use than
meperidine. In the article titled Meperidine Misuse in a Patient with Sphincter of Oddi
Dysfunction, a 55 year-old woman with a history of sphincter of Oddi dysfunction was admitted
to a hospital with severe abdominal pain, vomiting, diarrhea, and dysuria. She was admitted to
the hospital and started on intravenous meperidine for the pain. Her doses were as follows: 175
mg on day one, 700 mg on day two, 950 mg on day three, and 300 mg on day four. On day four,
she became disoriented and suffered a generalized seizure lasting 30-60 seconds. This was
presumably due to a build of normeperidine, a metabolite that forms as a result of the breakdown
of meperidine. Normeperidine is a toxin that acts as a CNS stimulant and has the potential to
cause agitation, irritability, nervousness, tremors, muscle twitches, myoclonus, and seizures. It
builds up in the body due to its long half-life of about 8-21 hours, which differs from
meperidines short half-life of 2-4 hours. The article then goes on to claim that No studies or
evidence indicate that meperidine is superior to morphine when treating pain in conditions
associated with the biliary tree, (Hubbard et al.). Due to the evident danger of using meperidine
that is illustrated in this article, recent research suggests that morphine may be more effective
and safer than meperidine.
Evidence Synthesis
Overall, older research focuses on the effects of meperidine and morphine related to pressures
within the common bile duct and sphincter of Oddi, which releases both bile and pancreatic
juices into the duodenum of the small intestine. These studies suggest that morphine may
increase pressures more so than meperidine, but do not confirm that this directly correlates to an
MEPERIDINE VERSUS MORPHINE 10
increase in pain. Therefore, these studies do not conclude that meperidine is a better opioid
analgesic for pain related to cholecystitis or pancreatitis. In addition to this, more recent research
claims that there is not sufficient evidence to suggest that meperidine is better than morphine. In
fact, some go to say that morphine may in fact be superior to meperidine based on a risk/benefit
ratio due to normeperidine build up and risk of seizures in meperidine use.
Clinical Research and Recommendations
More research is needed regarding the use of meperidine versus morphine in treatment of
biliary and pancreatic pain. Almost all of the research that compares the two opioid analgesics is
outdated and is contradictory in some cases. Although morphine was shown to increase the
pressure of the sphincter of Oddi, there is not evidence that this directly correlates to an increase
in pain level. There are also no studies that directly compare the two in terms of pressure or
perceived pain level. More studies are needed to determine the effects of these drugs on pain
levels of patients. Members of the healthcare team will not understand the full effect of these
drugs on pain related to cholecystitis and pancreatitis until this research is conducted.
Overall, however, it is important for nurses to realize how both morphine and meperidine
affect the patient and how they act in the body to alleviate pain. Based on these findings, it is
both the nurses and the doctors responsibility to understand the risks and benefits associated
with the use of each drug. Morphine may cause spasm of the sphincter of Oddi, which may or
may not increase pain. If pain does ensue, it may be only partially reversible by Naloxone, a
morphine-antagonist. Meperidine, on the other hand, may irritate the sphincter of Oddi to the
extent of morphine, but leads to build up of a toxin called normeperidine, which has the potential
to cause seizures. Thus, it is the nurses responsibility to be aware of these possible side effects
MEPERIDINE VERSUS MORPHINE 11
and intervene if necessary. Until more research is conducted to determine whether morphine or
meperidine is more effective in reducing pain, it may be more intelligent to use morphine, as
recent research suggests, due to the fact that it has a longer half-life and may be safer than
meperidine, which poses a risk for seizures.













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References
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