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Treatment of acute abdominal pain in the emergency room: A systematic

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Article  in  European journal of pain (London, England) · August 2014

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REVIEW ARTICLE

Treatment of acute abdominal pain in the emergency room:

A systematic review of the literature
C. Falch1*, D. Vicente2*, H. Häberle3, A. Kirschniak1, S. Müller1, A. Nissan4,5,6, B.L.D.M. Brücher4,5,7
1 Surgery, University of Tübingen, Germany
2 Department of Surgery, Walter Reed National Military Medical Center, Bethesda, USA
3 Department of Anesthesiology, University of Tübingen, Germany
4 INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy®, Germany – Israel – Serbia – USA
5 Theodor-Billroth-Academy®, Germany – Israel – USA
6 Department of Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
7 Bon Secours Cancer Institute, Richmond, USA

Correspondence Abstract
Björn L.D.M. Brücher
E-mail: b-bruecher@gmx.de Appropriate pain therapy prior to diagnosis in patients with acute abdomi-
nal pain remains controversial. Several recent studies have demonstrated
Funding sources that pain therapy does not negatively influence either the diagnosis or
None.
subsequent treatment of these patients; however, current practice patterns
Conflicts of interest
continue to favour withholding pain medication prior to diagnosis and
None declared. surgical treatment decision. A systematic review of PubMed, Web-of-
Science and The-Cochrane-Library from 1929 to 2011 was carried out
This paper contains original material that has using the key words of ‘acute’, ‘abdomen’, ‘pain’, ‘emergency’ as well as
not been previously published. different pain drugs in use, revealed 84 papers. The results of the literature
review were incorporated into six sections to describe management of
* Equal contribution.
acute abdominal pain: (1) Physiology of Pain; (2) Common Aetiologies of
Accepted for publication
Abdominal Pain; (3) Pre-diagnostic Analgesia; (4) Pain Therapy for Acute
12 December 2013 Abdominal Pain; (5) Analgesia for Acute Abdominal Pain in Special Patient
Populations; and (6) Ethical and Medico-legal Considerations in Current
doi:10.1002/j.1532-2149.2014.00456.x Analgesia Practices. A comprehensive algorithm for analgesia for acute
abdominal pain in the general adult population was developed. A review
of the literature of common aetiologies and management of acute abdomi-
nal pain in the general adult population and special patient populations
seen in the emergency room revealed that intravenous administration of
paracetamol, dipyrone or piritramide are currently the analgesics of choice
in this clinical setting. Combinations of non-opioids and opioids should be
administered in patients with moderate, severe or extreme pain, adjusting
the treatment on the basis of repeated pain assessment, which improves
overall pain management.

consensus regarding the timing of neither analgesia

1. Introduction
Treating acute abdominal pain in the emergency room
(ER) is one of the most frequent tasks faced by sur-
geons. Appropriate analgesia requires evaluation of
the individual patient’s pain, as well as a broad base of
knowledge of the pathophysiology of common causes
of abdominal pain and the pharmacology of appropri-
ate analgesic agents. Currently, there is no clear
nor the type of analgesic medications that should
be used to effectively manage acute abdominal pain.
This uncertainty largely stems from concerns that pre-
diagnostic analgesia may confound patient evaluation,
particularly the abdominal examination. This paper is
intended to provide physicians-in-training and expe-
rienced surgical specialists with an overview of
modern management of acute abdominal pain in adult

902 Eur J Pain 18 (2014) 902–913 © 2014 European Pain Federation - EFIC®
C. Falch et al.
What’s already known about this topic?
• Currently, there is no clear consensus regarding
the timing of analgesia, and the type of analgesic
medications that should be used to effectively
manage acute abdominal pain in the emergency
room.
Database?
• Medline, PubMed, Web-of-Science and The-
Cochrane-Library.
What does this study add?
• Clinical and practical evidence that the intrave-
nous administration of paracetamol, dipyrone or
piritramide are currently the analgesics of choice
in the emergency room treating patients with
acute abdominal pain.
• Combinations of non-opioids and opioids should
be administered in patients with moderate,
severe or extreme pain, adjusting the treatment
on the basis of repeated pain assessment, which
improves overall pain management.
patients based on results of a comprehensive pub-
lished literature review.
2. Methods
A systematic review of PubMed, Web-of-Science and The-
Cochrane-Library from 1929 to 2011 was carried out using
the terms (number of results of papers) ‘acute surgical
abdomen (n = 13,840), ‘acute abdominal pain’ (n = 17,324),
‘pain therapy’ (n = 193,129), ‘pain treatment’ (n = 354,789),
‘paracetamol’ (n = 17,842), ‘metamizole’ (n = 1504), ‘dipyrone’
(n = 1319), ‘NSAID’ (n = 177,007), ‘non-opioid analgesics’
(n = 279,034), ‘opioid analgesics’ (n = 6531), ‘emergency’
(n = 200,416), ‘emergency room’ (n = 13,009), ‘emergency unit’
(n = 12,809), ‘pre-operative pain therapy’ (n = 4351), ‘rescue
service’ (n = 1040), ‘pain and pregnancy’ (n = 15,683), ‘opioid-
dependence’ (n = 19,359), ‘drug addict’ (n = 346,827), pub-
lished in the English and German languages. Adding the
term ‘review’ produced a significant decrease in search
results according to the type of search term: ‘acute surgical
abdomen’ (n = 1954), ‘acute abdominal pain’ (n = 1874), ‘pain
therapy’ (n = 3236), ‘pain treatment’ (n = 50,147), ‘paraceta-
mol’ (n = 1879), ‘metamizole’ (n = 71), ‘dipyrone’ (n = 66),
‘NSAID’ (n = 18,851), ‘non-opioid analgesics’ (n = 24,194),
‘opioid analgesics’ (n = 92,617), ‘emergency’ (n = 22,792),
‘emergency room’ (n = 1104), ‘emergency unit’ (n = 1241), ‘pre-
operative pain therapy’ (n = 654), ‘rescue service’ (n = 113),
‘pain and pregnancy’ (n = 2214), ‘opioid-dependence’
(n = 2016), ‘drug addict’ (n = 37,823). Including a combina-
tion of the terms above as well as adding the search terms
© 2014 European Pain Federation - EFIC®
Acute abdominal pain therapy in emergency patients
‘physiology’ and ‘abdominal pain physiology’ under the
category of reviews dealing with current clinical practices
of acute abdominal pain management both pre- and post-
diagnosis revealed 84 papers.
3. Results
The results of the literature review are incorporated
into six sections to describe management of acute
abdominal pain: (1) Physiology of Pain; (2) Common
Aetiologies of Abdominal Pain; (3) Pre-diagnostic
Analgesia; (4) Pain Therapy for Acute Abdominal
Pain; (5) Analgesia for Acute Abdominal Pain in
Special Patient Populations, and (6) Ethical and
Medico-legal Considerations in Current Analgesia
Practices. The results of the literature review will also
be used to develop a comprehensive algorithm for
analgesia for acute abdominal pain in the general
adult population.
3.1 Physiology of pain
Acute pain is a normal and expected physiological
response to an adverse chemical, temperature-related
or mechanical stimulus associated with acute disease,
trauma or surgery (US Federation, 1999). It thus rep-
resents a physiological protective mechanism against
tissue-damaging effects. After tissue damage has
begun, pain largely loses its function as a warning
signal and – in addition to impairing overall well-
being – leads to stimulation of the somatic and sym-
pathetic nervous systems (Stork and Hofmann-Kiefer,
2009).
Tissue trauma releases hyperalgesic substances such
as bradykinins, prostaglandins, histamines, serotonin,
‘nerve growth factor’, hydrogen ions, adenosine tri-
phosphate (ATP), and immune cells, which lead to
activation of the nociceptive system and the initiation
of pain sensation (Carr and Goudas, 1999; Stork and
Hofmann-Kiefer, 2009). The impulses are transferred
via fast Aδ fibres and slower C fibres via the spinal cord
and brainstem to the thalamus (Gallacchi and Pilger,
2001). The thalamus then acts as the central distribu-
tor and transfers the incoming pain signals to the
limbic system, hypothalamus and hypophysis. The
resulting stress response is associated with a catabolic
state, tachycardia, hypertension, as well as nausea and
vomiting (Stork and Hofmann-Kiefer, 2009). Pain-
related avoidance behaviour, such as impaired mobi-
lization and hypoventilation, may also result. In
addition to the immediate hyperalgesia, chronic pain
and visceral hypersensitivity may develop due to local
inflammation, nociceptor sensitization and central
Eur J Pain 18 (2014) 902–913 903
Acute abdominal pain therapy in emergency patients
sensitization. Hence, timely and adequate pain control
will assist in decreasing pain-related complications and
achieving faster recuperation, with an associated
increase in patient satisfaction, quality of life and
overall reduced health-care costs (Kehlet and Holte,
2001; Wilder-Smith et al., 2002; Kehlet, 2004; Reichl
and Pogatzki-Zahn, 2009).
3.2 Common aetiologies of abdominal pain
The term ‘acute abdominal pain’ is often used syn-
onymously with ‘acute abdomen’; however, since
acute abdomen often leads to emergency surgery, it is
important to differentiate the terms (Grundmann
et al., 2010). ‘Acute abdomen’ is a time-sensitive term
for an acutely painful condition in the abdominal
cavity, which cannot initially be specified as a non-
surgical or surgical aetiology until the final diagnostic
assessment has been made (Siewert and Brauer,
2007). Acute abdomen can manifest as a complex of
symptoms including ‘abdominal pain’, ‘peritoneal
symptoms and/or signs’, and/or ‘disturbed circulatory
regulation’, and requires emergent therapeutic
intervention.
In contrast, acute abdominal pain is a broader term
that refers to the nociceptive pain response from both
emergent acute abdominal aetiologies and more
benign indolent processes. The most frequent causes
of acute abdominal pain seen in the ER are non-
specific abdominal pain (22.0–44.3%), acute appendi-
citis (15.9–28.1%), biliary disease (2.9–14.0%),
gastrointestinal perforation (2.3–15.0%), adynamic
ileus (4.1–8.6%), diverticulitis (8.2–9.0%), pancreati-
tis (3.2–4.0%), ureteral colic (5.1%) and inflamma-
tory bowel diseases (0.6%) (De Dombal, 1988; Attard
et al., 1992; Miettinen et al., 1996; Strömberg et al.,
2007). Many of the reviews on acute abdominal pain
(Lankisch et al., 2006; Grundmann et al., 2010;
Trentzsch et al., 2011) are based on a small number of
original studies – e.g., the largest study, including
more than 10,000 patients, conducted by the World
Gastroenterology Organization dating from 1986, was
based on data obtained from Finland (De Dombal,
1988; Miettinen et al., 1996). Actual data from Chapel
Hill, which investigated the relationship between pain
intensity and patient satisfaction in 88 patients who
had been treated with opioid analgesics revealed no
statistical correlation between pain intensity and
patient satisfaction (Phillips et al., 2013); the authors
concluded, that future investigations should use
intensity scores together with measurement of patient
satisfaction.
904 Eur J Pain 18 (2014) 902–913
C. Falch et al.
3.3 Pre-diagnostic analgesia
There is a prevailing view, particularly among sur-
geons (Graber et al., 1999; Nissman et al., 2003), that
pre-diagnostic analgesia in patients with acute
abdominal pain obscures the clinical symptoms and
signs, and thereby has a negative effect on treatment
decisions (Nissman et al., 2003). This, in turn, often
leads to analgesia being initially withheld from the
patient with acute abdominal pain (LoVecchio et al.,
1997; Grundmann et al., 2010). These concerns on the
part of the surgeon date back to the turn of the 20th
century, when abdominal pain was regarded as the
only constant symptom available for establishing a
diagnosis, and basing a surgical decision (Cope, 1929).
McHale and LoVecchio noted in 2001 that in the
absence of prospective studies up to the mid-1980s,
withholding of opioid pain therapy in patients with
acute abdominal pain was based on dogma and belief,
rather than established facts (McHale and LoVecchio,
2001).
In addition to these fears, patients may receive inad-
equate pain therapy due to communication problems,
concerns over side effects from analgesics and crowd-
ing of patients in ERs (Stork and Hofmann-Kiefer,
2009). The described fears and barriers have led to
significant delays in appropriate pain management as
revealed by Mills et al. who demonstrated that almost
50% of patients with abdominal pain only received
pain medication more than an hour after admission to
the ER (Mills et al., 2009). Ultimately, these delays and
inadequate dosing of analgesia have impacted patient
care and patient satisfaction. In comparison with post-
operative analgesia, which has a patient satisfaction
level of more than 90% (Saur et al., 2008), patient
satisfaction with preoperative pain therapy remains
inadequate, only 40–60% (Marinsek et al., 2007;
Jawaid et al., 2009). Interestingly, this discrepancy in
pre-diagnostic analgesia has not been evident in
recent studies of trauma patients, in whom the focus
for many decades has been directed to prompt diag-
nosis with laboratory and imaging studies (Jawaid
et al., 2009). Evaluating the adequacy of preoperative
analgesia and patient’s satisfaction at an accident and
emergency department revealed that there was signifi-
cantly less prescription of analgesic to patients with
acute abdomen (47.1%) as compared to trauma
patients (73.5%; p = 0.001) (Jawaid et al., 2009).
In contrast to the described beliefs and fears, the
published evidence-based literature supports pre-
diagnostic administration of analgesia in the setting of
acute abdominal pain. Several studies (Attard et al.,
1992; Pace and Burke, 1996; LoVecchio et al., 1997;
© 2014 European Pain Federation - EFIC®
C. Falch et al.
Vermeulen et al., 1999; Mahadevan and Graff, 2000;
Thomas et al., 2003; Gallagher et al., 2006; Amoli
et al., 2008) and one Cochrane review published in
2007 (Manterola et al., 2007), which was updated in
2011 (Manterola et al., 2011), have demonstrated that
administering analgesia for acute abdominal pain is
appropriate prior to the diagnosis regardless of the
aetiology of the abdominal pain. The authors of the
Cochrane review concluded that the use of opioid
analgesics neither increased the risk of misdiagnosis
nor increased the risk of incorrect treatment decisions
being made; the Cochrane reviewers furthermore
stated that pain therapy may, in fact, make the clinical
examination easier in patients with an acute
abdomen. Based on these results, the authors of this
paper recommend early pre-diagnostic administration
of analgesia in the assessment and treatment of acute
abdominal pain.
3.4 Pain therapy for acute abdominal pain
Management of acute abdominal pain for the general
adult population in the ER requires different variables
(Stork and Hofmann-Kiefer, 2009): (1) rapid initial
evaluation of pain intensity; (2) administration of the
appropriate analgesic agent by the appropriate route
based on the clinical scenario; and (3) early imple-
mentation of adjuvant measures, which afterwards
should be repeated for a continuous pain assessments
to guide further analgesia.
No pain
0 1
No pain
Figure 1 One-dimensional pain scales depict- No pain
ing examples of pain ratings. Pain is assigned
to a range between 0 and 100 mm (VAS), a
selection of possible answers (VRS), a numeri- D
cal value between 0 and 10 (NRS), or a facial
expression (SAS). (A) Visual analogue scale
(VAS). (B) Numerical rating scale (NRS). (C)
0 1
Verbal rating scale (VRS). (D) The ‘Smiley’ ana- No pain
logue scale (SAS).
© 2014 European Pain Federation - EFIC®
Acute abdominal pain therapy in emergency patients
3.4.1 Pain intensity assessment
Initial evaluation of patients with acute abdominal
pain should rapidly and objectively assess the intensity
of the pain in order to guide appropriate pain man-
agement. The intensity of pain is a subjective percep-
tion, which does not correlate with clinical findings,
laboratory parameters or diagnostic imaging findings.
In point of fact, several studies have demonstrated that
the medical staff underestimate patient pain in com-
parison with the patient’s appraisal themselves
(Striebel et al., 1992; Mäntyselkä et al., 2001; Davoudi
et al., 2008). Simple and repeatable pain measure-
ments using one-dimensional and multidimensional
scales have been developed for objective assessment of
individual pain perception. One-dimensional scales
such as the visual analogue scale (VAS), verbal rating
scale (VRS) and numerical rating scale (NRS), as well
as the ‘Smiley analogue scale’ (SAS) are used in the
acute setting (Fig. 1) (Todd et al., 1996; Kelly, 1998;
Gallagher et al., 2001; Marinsek et al., 2007; Amoli
et al., 2008; Daoust et al., 2008; Jawaid et al., 2009;
Sharwood and Babl, 2009). Limitations for pain mea-
surement include disturbances of consciousness,
impaired vision and language barriers (Gallagher
et al., 2001). These clinical scenarios may make it nec-
essary to carefully select the scale used according to
the patient’s unique personal circumstance. Due to its
ease of use, with a low rate of error and a high level of
acceptance and sensitivity, the NRS shows the best
Worst imaginable
pain
2 3 4 5 6 7 8 9 10
Worst imaginable
pain
Mild pain Moderate pain Severe pain Very severe Worst imaginable
pain pain
2 3 4 5
Worst imaginable
pain
Eur J Pain 18 (2014) 902–913 905
Acute abdominal pain therapy in emergency patients
results in adults (Aubrun et al., 2003; Herr et al., 2004;
Gagliese et al., 2005); hence, the NRS is the objective
scale recommended in this paper.
3.4.2 Route of administration
Non-opioid and opioid analgesics are readily available,
with various forms of administration. In all clinical
scenarios, the route of administration of the analgesic
agent should be determined relative to the estimated
potential for enteric absorption of the delivered agent.
Sympathoadrenergic stress reactions during acute
pain and an increase in intraluminal pressure during
adynamic ileus and intestinal obstruction to more
than 30 mmHg can lead to reduced gastrointestinal
motility and microcirculatory disturbances, which
impair absorption of orally and rectally administered
medications (Feifel, 1985; Stork and Hofmann-Kiefer,
2009). In cases of acute abdominal pain in which
compromised enteric absorption is suspected, intrave-
nous analgesic administration should be achieved in
order to bypass the gastrointestinal system and attain
rapid onset of effect (Feifel, 1985; Stork and
Hofmann-Kiefer, 2009). Alternative parenteral
administration routes, such as intramuscular injection,
should be avoided given the potential risks of neural
and vascular injury, but may be necessary for prompt
pain relief if intravenous access cannot be obtained
(Greenblatt and Koch-Weser, 1976; Müller-Vahl,
1983; Tong and Haig, 2000; Deutsche Interdisziplinäre
Vereinigung für Schmerztherapie (DIVS) et al., 2008).
3.4.2.1 Opioid analgesics
Opioid medications are derived from opioid alkaloids
and bind to opioid receptors both in the central
nervous system as well as in peripheral tissues to
provide pain relief (Stork and Hofmann-Kiefer, 2009).
Each pharmaceutical opioid has a unique analgesic
potency and side effect profile, which impact dosing
and clinical indications for that medication. In the
setting of severe acute abdominal pain, a strong-acting
opioid, such as morphine, is required. Weak opioids
(e.g., tramadol and tilidine) are not considered
adequate first-line agents in the treatment of acute
abdominal pain, given that they have a well-
recognized maximum daily dosage with attendant
short duration of effect (Deutsche Interdisziplinäre
Vereinigung für Schmerztherapie (DIVS) et al., 2008).
Also, Pethidine (meperidine), a weak opioid, was
previously used for treating acute biliary pain;
however, it is no longer recommended due to the risk
of accumulation of its active neurotoxic metabolite,
906 Eur J Pain 18 (2014) 902–913
C. Falch et al.
norpethidine, and its relatively short duration of effect
(Greenblatt and Koch-Weser, 1976). Piritramide,
conversely, is a potent intravenous opioid with a
long duration of effect, and no clinically esta-
blished maximum dosage. It has demonstrated excel-
lent results in post-operative analgesia (Deutsche
Interdisziplinäre Vereinigung für Schmerztherapie
(DIVS) et al., 2008); it thereby lends itself well to
pre-diagnostic analgesia. As seen in Table 1, piritr-
amide, should be administered in small doses and
titrated to effect in order to keep side effects as low as
possible (Deutsche Interdisziplinäre Vereinigung für
Schmerztherapie (DIVS) et al., 2008; Stork and
Hofmann-Kiefer, 2009).
3.4.2.2 Side effects and complications of opioid
analgesics and their treatment
The wide range of tissues with opioid receptors allows
for effective analgesia with opioid agents, but this also
leads to potential side effects in almost all organ
systems, which occur in a dose-dependent fashion
(Schug et al., 1992; Tramèr, 2001; Harris, 2008; Stork
and Hofmann-Kiefer, 2009). Particular to opioid
dosing for acute abdominal pain, respiratory depres-
sion and nausea and vomiting are the most relevant
side effects.
Respiratory depression is the most feared side effect
of these medications; however, concerns of causing
respiratory depression are usually unfounded, as
alterations in vital signs are rare (Kanowitz et al.,
2006), and the pain itself is one of the most effective
antagonists to this side effect (Stork and Hofmann-
Kiefer, 2009). In a retrospective analysis of some 2000
patients who received pre-hospital treatment with
fentanyl, Kanowitz et al. reported that only 0.6% of
the patients showed any alteration in vital signs, but
the evaluation of the pain scales before and after
fentanyl application revealed a significant change
from 8.4 to 3.7 (p < 0.0001) (Kanowitz et al., 2006).
Despite this rare occurrence, it is safe and prudent
clinical practice to titrate strong opioids in order to
minimize respiratory and circulatory depression.
Treatment for respiratory depression and cardiovascu-
lar complications primarily involves oxygenation and
ventilation, as well as circulation-stabilizing measures
such as volume substitution and administration of cir-
culatory support drugs (theodrenaline/cafedrine) as
needed (Table 1). As a supplementary measure, the
opioid effect can be antagonized with naloxone
(Table 1) (Deutsche Interdisziplinäre Vereinigung für
Schmerztherapie (DIVS) et al., 2008; Harris, 2008);
however, it should be noted that at high dosages, the
© 2014 European Pain Federation - EFIC®
 Table 1 Analgesics, supplements and medications used to treat SEs and complications of analgesics for acute abdominal pain in adults in the emergency room.

Maximum daily Onset of

Agent Indication Single dose dosage effect Half-life Relevant SE and CI Remarks
C. Falch et al.

Non-opioid analgesics (intravenous administration)

Paracetamol Sole agent for mild pain.
(acetaminophen) Should be used in
combination with opioid for
moderate to extreme pain.
Dipyrone (metamizole) Sole agent for mild pain.
500–1000 mg 4000 mg 10–15 min 1–2 h CI: known hypersensitivity, severe Short infusion for 15 min; do
disturbance of liver function (e.g., in not mix with other drugs
chronic alcohol abuse), G6PD
1000–2500 mg 5000 mg 20–30 min 1.8–4.6 h SE: agranulocytosis (very rare) Short infusion for 15 min;

© 2014 European Pain Federation - EFIC®

Should be used in
combination with opioid for
moderate to extreme pain.
Strong-acting opioid analgesics (intravenous administration)
Piritramide To be used in combination
with non-opioid analgesics
in moderate to extreme
pain
Opioid antagonists (intravenous administration)
Naloxone Opioid antagonism in states
of central nervous sedation
(respiratory depression)
Medications to treat opioid-induced nausea and vomiting (intravenous administration)
Metoclopramide Nausea, vomiting
Ondansetron Nausea, vomiting
Medication for circulatory support for opioid-induced hypotension
Theodrenaline/cafedrine Hypotension refractory to
volume substitution
Spasmolytic (intravenous administration)
Butylscopolamine bromide Spasmolytic,
parasympatholytic
CI: known hypersensitivity, hypotension, hypotension with rapid
dyshematopoiesis, G6PD deficiency, infusion
acute intermittent hepatic porphyria,
renal insufficiency (dose reduction
required)
3.75–22.5 mg – 2–5 min 4–10 h CI: known hypersensitivity Slow i.v. (10 mg/min) or short
SE: sedation, respiratory depression, infusion → titrate!
hypotension, nausea, vomiting
0.1–0.2 mg – 70 min CI: known hypersensitivity 0.1 mg every 2 min,
SE: nausea, tachycardia, hypotension, depending on effect
hypertension
10 mg 30 mg 2.6–4.6 h CI: known hypersensitivity, Inhibition of central dopamine
pheochromocytoma, and serotinin-3 receptors
prolactin-dependent tumors,
mechanical ileus, epilepsy
4–8 mg 3.2–3.5 h CI: known hypersensitivity Blockade of central 5-HT3
receptors
0.5–1.0 ampoule 1h SE: angina pectoris, ventricular cardiac 0.5–1.0 ampoule (1–2 mL)
(1–2 mL) rhythm disturbances, palpitations slowly i.v. (1 mL/min)
CI: angle-closure glaucoma,
pheochromocytoma
20–40 mg (1–2 mL) 5.1 h SE: vertigo, hypotension Slow i.v.
CI: mechanical stenoses of the
gastrointestinal tract, angle-closure
glaucoma, myasthenia gravis

Eur J Pain 18 (2014) 902–913

CI, contraindication; G6PD, glucose-6-phosphate dehydrogenase deficiency; SE, side effect.

907
Acute abdominal pain therapy in emergency patients
Acute abdominal pain therapy in emergency patients
narrow therapeutic window for naloxone causes a
reduction in the analgesic effect of opioids in the
central nervous system, and can be associated with
significant exacerbation of pain for the patient.
Nausea and vomiting are common side effects of
opioid analgesia. Treatment for these side effects
depends on the receptors involved, and is mainly
based on treatment of post-operative opioid-related
nausea and vomiting (Tramèr, 2001; Apfel et al., 2004;
Büttner et al., 2004; Harris, 2008). Ondansetron and
metoclopramide, as seen in Table 1, are effective
agents to treat opioid-induced nausea and vomiting
(Tramèr, 2001; Apfel et al., 2004; Büttner et al., 2004;
Wallenborn et al., 2006). Alternative agents to treat
narcotic-associated nausea and vomiting in this setting
include droperidol, haloperidol and dexamethasone.
For patients with treatment-resistant symptoms, the
use of combinations of agents to achieve synergistic
effects has been discussed (Harris, 2008; Rittner and
Brack, 2011).
3.4.2.3 Non-opioid analgesics
Non-opioid analgesic agents are divided into acidic
and non-acid anti-pyretic analgesics (Brune and
Zeilhofer, 1999). Acidic anti-pyretic analgesics mainly
accumulate in tissues with a low pH, such as tissue
with active inflammatory processes, the kidneys and
the stomach, whereas non-acidic analgesics distribute
to all tissues (Brune and Zeilhofer, 1999). The main
representatives of acidic anti-pyretic analgesics are
non-steroidal anti-inflammatory drugs (NSAIDs)
(Brack et al., 2004). Non-acidic anti-pyretic analgesics
include pyrazolones [e.g., dipyrone (metamizole) ]
and anilines [e.g., paracetamol (acetaminophen) ]
(Brack et al., 2004). These non-opioid medications
induce both central and peripheral analgesic effects by
inhibiting cyclooxygenase and reducing prostaglandin
(PG) synthesis (Stork and Hofmann-Kiefer, 2009;
Toussaint et al., 2010).
In contrast to the majority of the non-opioid analge-
sics currently available, paracetamol and dipyrone can
be administered parenteral (Bannwarth and Péhourcq,
2003; Deutsche Interdisziplinäre Vereinigung für
Schmerztherapie (DIVS) et al., 2008) with rapid onset
of action, and thereby represent the two preferable
non-opioid analgesics in patients with acute abdominal
pain. As seen in Table 1, these non-opioid medications
have unique analgesic, anti-pyretic and anti-
inflammatory effects, as well as adverse side effect
profiles and contraindications (Elia et al., 2005;
McGettigan and Henry, 2006; Stork and Hofmann-
Kiefer, 2009; Toussaint et al., 2010; Zahn et al., 2010).
908 Eur J Pain 18 (2014) 902–913
C. Falch et al.
The recommended dosing to achieve pain relief with
a single dose is described in Table 1, as well as the
maximum daily doses to mitigate renal toxicity with
dipyrone (Abu-Kishk et al., 2010) and hepatotoxicity
with paracetamol, respectively.
Combinations of non-opioids, particularly NSAIDs
and paracetamol, remain controversial. Lange et al.
analysed 25 randomized controlled trials and investi-
gated if a combination of different non-opiods would
have an advantage of an improved analgesia regimen
and/or would lead to a reduction of opiod-related
adverse effects (Lange et al., 2007). Only three out of
25 trials revealed improved analgesic efficacy and
therefore the authors concluded that a combination of
non-opiod-analgesics cannot be recommended at the
present time. In contrast, combinations of opioids with
non-opioid analgesics improve the quality of analgesia
and allow for a reduced opioid dosage, with an overall
reduction in opioid-associated side effects such as
nausea, vomiting and respiratory depression (Dahl
et al., 1990; Elia et al., 2005; Marret et al., 2005; Stork
and Hofmann-Kiefer, 2009).
3.4.2.4 Significant side effects of non-opioid
analgesics and their treatment
While most side effects of non-opioid medications are
relatively benign, particularly for single-dose adminis-
tration of the agent, there is a known incidence of less
than one case in 1,000,000 of agranulocytosis after
administration of dipyrone (Ibáñez et al., 2005). For
this reason, dipyrone is not available in all countries,
and typically requires prescription in countries where
it is available. Initial patient evaluation should rule out
a history of dyshematopoesis, when possible, prior to
administering dipyrone (Bannwarth and Péhourcq,
2003).
3.4.2.5 Spasmolytics
In cases of colicky abdominal pain such as biliary or
ureteral colic, spasmolytic (parasympatholytic) agents
such as butylscopolamine bromide (Table 1) should be
considered (Makharia, 2011). There is no clear con-
sensus in the literature regarding the optimal analgesic
agent for acute colicky abdominal pain prior to diag-
nosis. While butylscopolamine demonstrated excel-
lent analgesia for biliary colic (Tytgat, 2008), it was not
as effective in relieving pain in renal colic patients
when compared to dipyrone (p < 0.05) (Stankov et al.,
1994). Further, combinations of butylscopolamine and
dipyrone did not potentiate analgesia (Edwards et al.,
2002). In this light, butylscopolamine should not be
© 2014 European Pain Federation - EFIC®
C. Falch et al. Acute abdominal pain therapy in emergency patients

used as a first-line analgesic agent in treating acute
abdominal pain, but rather as a supplementary
measure for colicky abdominal pain after initial
administration of analgesia.
3.4.2.6 Appropriate timing and dosing of analgesics,
and reassessment of pain intensity
Once the patient-reported pain intensity has been
assessed on the NRS scale, a targeted management
approach should be implemented to appropriately
treat the pain. The level of pain intensity at which
analgesia should be administered remains a matter of
controversy in the literature. Stork and Hofmann-
Kiefer do not believe that there is a compelling indi-
cation for pain therapy preclinically at intensity of ≤3
on the NRS (Stork and Hofmann-Kiefer, 2009). Other
authors (Trentzsch et al., 2011), the most recent S3
guidelines on the treatment of acute perioperative
and post-traumatic pain (Deutsche Interdisziplinäre
Vereinigung für Schmerztherapie (DIVS) et al., 2008),
and the authors of this paper recommend adminis-
tering non-opioid analgesic agents at a pain intensity
of NRS ≤ 3 (Trentzsch et al., 2011), and a combina-
tion of non-opioids and opioids at an intensity of
NRS > 3 (Deutsche Interdisziplinäre Vereinigung für
Schmerztherapie (DIVS) et al., 2008).
After initial management of abdominal pain,
repeated pain assessment will help improve and titrate
pain therapy to effect (Stork and Hofmann-Kiefer,
2009). Evaluation of pain intensity should be repeated
every 15–30 min, depending on the onset of effect and
efficacy of the analgesic agent used. Dosing and timing
of appropriate analgesics per intensity level as well as
analgesia supplements based on pain characteristic
(e.g., colicky abdominal pain) are illustrated in algo-
rithmic format in Fig. 2.
3.4.3 Adjuvant measures
In cases of acute abdominal pain, patient positioning
that relieves tension on the abdominal wall may
help reduce pain. Measurable reductions in pain
can also be achieved by offering sympathy, and
providing a competent, reassuring and solution-
oriented presence (Hofmann-Kiefer et al., 1998;
Stork and Hofmann-Kiefer, 2009). Adjuvant mea-
sures should be initiated early in the preclinical and
pre-diagnostic settings to maximize benefit to the
patient.

Acute abdominal pain

Pain intensity measurement and clinical assessment

NRS 1–3 (mild pain) NRS 4–5 (moderate pain) NRS 6–7 (severe pain) NRS ≥ 8 (extreme pain)

1 g paracetamol* i.v. 1 g paracetamol* i.v. as a 1 g paracetamol* i.v. as a Try:

as a short infusion short infusion over 15 min
over 15 min
OR
OR
2.5 g dipyrone** i.v. as a
1 g dipyrone** i.v. as short infusion over 15 min
a short infusion over (preferable in colicky pain)
15 min (preferable in Consider adding 3.75–
colicky pain) 7.5 mg piritramide*** i.v.
as a short infusion over
15 min
short infusion over 15 min
AND
7.5 mg piritramide** i.v.
as a short infusion over
15 min
OR
2.5 g dipyrone** i.v. as a
short infusion over 15 min
(preferable in colicky pain)
1 g paracetamol* i.v. as a
short infusion over 15 min
AND
7.5–15.0 mg piritramide
i.v. as a short infusion over
15 min
OR
2.5 g dipyrone i.v. as a
short infusion over 15 min
(preferable in colicky pain)

AND AND
7.5 mg piritramide*** i.v. 7.5–15 mg piritramide i.v.
as a short infusion over as a short infusion over 15 min
15 min OR
Titration with repeated
administration of 3.75 mg
piritramide i.v.
Consultation with
anesthesiologist

Supplements: For colicky pain consider 20 mg butylscopolamine bromide slowly i.v.

Figure 2 Algorithm for pre-diagnostic analge-
sia of acute abdominal pain in general adult
population.
Repeat clinical examination if not possible before pain treatment
Repetition of pain measurement after 15 min for pirtramide and 30 min for paracetamol and dipyrone→
Modification of pain therapy following algorithm
*Paracetamol maximum daily dose: 4g
**Dipyrone maximum daily dose: 5g
***Piritramide has no established maximum daily dose. Titrate analgesia per algorithm and monitor for
cardiopulmonary and nausea/vomiting side effects.

© 2014 European Pain Federation - EFIC® Eur J Pain 18 (2014) 902–913 909
Acute abdominal pain therapy in emergency patients
3.5 Analgesia for acute abdominal pain in
special patient populations
3.5.1 Pregnancy
Many drugs are not approved for use in pregnant
patients, not because there is evidence that they are
teratogenic, but rather because of a lack of evidence
that they are safe for the foetus (Østensen and Förger,
2009). Paracetamol has no known teratogenicity or
embryotoxicity (Briggs, 1998), and it can be adminis-
tered throughout pregnancy and breastfeeding; it is
therefore the non-opioid analgesic of choice in these
patients (Greenblatt and Koch-Weser, 1976; Østensen
and Förger, 2009; Scialli et al., 2010). Dipyrone is cur-
rently still regarded as being contraindicated during
the first trimester (gestational weeks 1–13) and third
trimester (gestational weeks 27–40), but it may be
administered in the second trimester (gestational
weeks 14–26) (Deutsche Interdisziplinäre Vereinigung
für Schmerztherapie (DIVS) et al., 2008). A recent
retrospective analysis has shown that there is no risk
of teratogenic effect with dipyrone during pregnancy,
and that this drug is not associated with intrauterine
death, premature birth or low birthweight (Da Silva
Dal Pizzol et al., 2009). Ibuprofen and diclofenac can
be administered in the first and second trimesters
(Greenblatt and Koch-Weser, 1976; Wilffert et al.,
2011), but there is a relative contraindication for them
in the third trimester (Deutsche Interdisziplinäre
Vereinigung für Schmerztherapie (DIVS) et al., 2008).
As ibuprofen is not transferred to breast milk, it is
regarded as safe during breastfeeding and is therefore
the NSAID of choice in this setting (Greenblatt and
Koch-Weser, 1976; Risser et al., 2009).
There are no randomized controlled trials available
on preoperative pain therapy to evaluate opioid anal-
gesia for acute abdominal pain during pregnancy and
breastfeeding. However, piritramide should be consid-
ered in this setting based on successful post-operative
pain therapy results for these patients (Deutsche
Interdisziplinäre Vereinigung für Schmerztherapie
(DIVS) et al., 2008). Patients who are breastfeeding
should only resume breastfeeding ≥24 h after the last
dose of piritramide (Deutsche Interdisziplinäre
Vereinigung für Schmerztherapie (DIVS) et al., 2008).
It is important to note that opioid analgesics adminis-
tered as long-term therapy and during birth can lead
to withdrawal syndromes (Schaefer and Weber-
Schöndorfer, 2009). Sudden withdrawal of opioids
that have been taken for a prolonged period during
pregnancy can trigger intrauterine abstinence syn-
drome and neonatal abstinence syndrome (McCarthy,
910 Eur J Pain 18 (2014) 902–913
C. Falch et al.
2012). There is inadequate data on the effects on
the foetus of short-term administration of opioid
analgesics.
3.5.2 Patients with opioid tolerance and/or
drug dependency
Patients with opioid tolerance often report severe pain
perioperatively, and require more analgesics over a
longer period (Rittner and Brack, 2011). All patients
who become accustomed to opioids develop physical
dependency and tolerance. Psychological dependence
and addiction, however, usually only develop in cases
of opioid abuse. Associated physical and psychological
factors in opioid abuse patients may make it difficult to
distinguish between pain, opioid withdrawal and psy-
chiatric pathology. Concern over increased depen-
dency in opioid-tolerant patients is not usually
justified in the management of acute abdominal pain,
and withdrawal should not be attempted periopera-
tively (Rittner and Brack, 2011). To avoid inadequate
or inappropriate care, early interdisciplinary collabo-
ration, and if necessary psychological or psychiatric
involvement in the patient’s care, should be sought. In
opioid-addicted patients, perioperative withdrawal
symptoms may require treatment with L-methadone,
perhaps in addition to intravenous clonidine (0.5–
2.0 μg/kg body weight per hour). Former drug addicts
do not require withdrawal prophylaxis.
3.6 Ethical and medico-legal consideration in
current analgesia practices
In addition to the clinical benefits of appropriate anal-
gesia, there are also ethical and legal obligations to the
patient. Giesa et al. point out that failure to provide
adequate pain treatment may count as failure to
render assistance in an emergency (Section 323c of the
German Criminal Code) (Giesa et al., 2007). In terms
of professional regulations, the duty to relieve pain is
stipulated in Section 1, Paragraph 2 of the professional
code of conduct for physicians in Germany. It has been
stated, that inadequate pain therapy due to poor train-
ing or time shortages makes the hospital trust manage-
ment culpable for failure to provide an adequate
organizational system (Biermann, 1999; Giesa et al.,
2007).
4. Summary and recommendations
In summary, our comprehensive review of the lite-
rature revealed that abdominal pain is the most fre-
quent reason for acute pain therapy in emergency
© 2014 European Pain Federation - EFIC®
C. Falch et al.
departments relevant to the general surgeon.
Untreated pain affects patient comfort and impairs the
organism, with sometimes far-reaching and enduring
negative consequences (Amoli et al., 2008). In this
light, every patient should be offered adequate and
timely pain therapy when indicated. Unfortunately,
prevalent concerns remain over administration of
analgesics fearing that they may negatively influence
diagnosis and management of acute abdominal pain
(LoVecchio et al., 1997; Grundmann et al., 2010).
Notably, the net result is that up to three-quarters of
all these patients initially have analgesics withheld
from them (Jawaid et al., 2009). In contrast to these
fears, several evidence-based studies (Attard et al.,
1992; Pace and Burke, 1996; LoVecchio et al., 1997;
Vermeulen et al., 1999; Mahadevan and Graff, 2000;
Thomas et al., 2003; Gallagher et al., 2006; Amoli
et al., 2008), and one Cochrane review (Manterola
et al., 2011), support prompt analgesia administration
prior to the aetiological diagnosis of acute abdominal
pain patients. Pain therapy should, therefore, no
longer be withheld from or delayed for these patients,
and it should be initiated prior to diagnosis after
assessment of relevant pain characteristics, by admin-
istering the most appropriate analgesic agents in a
timely manner. This process includes:
(1) Focused assessment of the intensity of pain with
NRS (Fig. 1B).
(2) Intravenous analgesia:
(a) Non-opioid (dipyrone or paracetamol) for
NRS ≤ 3
(b) Combination of opioids (piritramide) and
non-opioids for NRS > 3
(c) Consideration of supplementing analgesia
with a spasmolytic (butylscopolamine
bromide) if renal or biliary colic is suspected.
(3) Early initiation of adjuvant measures to promote
patient comfort.
(4) Repeated NRS pain intensity evaluations every
15–30 min, as well as identification and treatment of
analgesic side effects and complications.
These recommendations are illustrated in a clinical
decision support algorithm in Fig. 2. While the algo-
rithm applies well to the general adult population, the
patient population seen in the ER for acute abdominal
pain is heterogeneous and several considerations must
be taken into account on their behalf. Alternative
analgesic strategies should be considered for both
special patient populations (as described above) and
for contraindications (e.g., allergies) to the recom-
mended analgesic agents. Further, closer monitoring
should be implemented in cases of cardiovascular or
pulmonary suppression attributable to either the
© 2014 European Pain Federation - EFIC®
Acute abdominal pain therapy in emergency patients
underlying abdominal pathology or patient comor-
bidities, particularly when administering opioids.
Author contributions
All authors substantially contributed to the (1) conception
and design; (2) drafting and critical revising of the paper; and
(3) final approved the submitted version.
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