Running head: POST-OPERATIVE PAIN

Post-Operative Pain: Exploring the Use of Intravenous Acetaminophen

Lacey Burke
Clemson University

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Abstract

Purpose: The purpose of this paper is to explore the effects of IV acetaminophen on pain
control, describe the advantages and disadvantages of IV acetaminophen compared to current
postoperative pain medications used, and discuss implications for nursing practice, education,
and research.
Methods: A systematic literature review was conducted using Medline and CINAHL
databases. The electronic database search yielded an acceptable number of articles in which 15
articles were chosen for literature review.
Results: Although the goal was to find literature that supported postoperative IV
acetaminophen use in the cardiac surgical patient, an inadequate number of articles were found in
cardiac surgery alone. Only six articles were found that supported IV acetaminophen use in
cardiac surgery while the remaining number of articles supported IV acetaminophen use in
abdominal, orthopedic, and gynecological surgeries. The systematic literature review revealed
several common themes among the surgical population of which included acetaminophen
benefits, safety of acetaminophen, and decreased postoperative complications.
Conclusions: Acetaminophen is a non-opioid medication that helps to provide sustained
pain relief. Acetaminophen use provides decreased postoperative complications when compared
to narcotics. It was found to decrease nausea and vomiting, decrease hospital length of stay,
quicken extubation time due to less airway obstruction, quicken mobilization after surgery,
accelerate removal of chest drainage tubes, and decrease oxidative stress that leads to acute renal
failure.
Keywords: cardiac, post-operative, paracetamol, acetaminophen, heart, surgery, pain.

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Post-Operative Pain: Exploring the Use of Intravenous Acetaminophen

Postoperative pain causes decreased healing and results in several complications
including tachycardia, hypertension, and ileus (Upadya, Pushpavathi, & Seetharam, 2015).
Managing postoperative pain with narcotics, however, can be problematic. While opioid
medications help to control pain, they have many side effects including respiratory depression,
nausea, vomiting, sedation, itching, and constipation (Upadya et al, 2015). These adverse effects
delay mobility and slow the healing process (Upadya, et al, 2015). Finding a pain medication that
relieves pain without interfering with care and decreasing alertness can be challenging.
Intravenous (IV) acetaminophen (paracetamol) is a nonopioid analgesic used for many
types of pain (Raffa, Pergolizzi, Taylor, Decker, & Patrick, 2013, p. 668). Oral acetaminophen
has been used for almost a century, but the FDA recently approved IV acetaminophen in 2010
(Raffa et al, 2013). Although acetaminophen is an older drug, the exact mechanism of action is
unknown (Baley, Michalov, Kossick, & McDowell, 2014). It is thought that acetaminophen is
active in both the central and peripheral nervous systems (Baley et al, 2014).
The adult dose is 1,000 milligrams every six hours with a maximum dose of four grams
per day (Baley et al, 2014, p 61). The onset and peak action of the drug when given IV is less
than 15 minutes and the duration is six hours (Baley et al, 2014).
Several studies have shown the positive effects of intravenous acetaminophen in
controlling post-operative pain with a variety of surgeries (Macario & Royal, 2010). A recent
study found that IV acetaminophen provided relief of pain following gynecological, abdominal,
back, thyroid, dental, orthopedic, and eye surgeries (Macario & Royal, 2010), however, little is
known about the effects of scheduled IV acetaminophen for postoperative pain in cardiac
surgical patients, particularly those with coronary artery bypass grafting (CABG).

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There are over 500,000 CABG surgeries performed in the United States each year with an
average length of stay of eight days (Bypass surgery, 2015) (Coronary artery, 2014).
Approximately one third of patients are women, and two thirds of patients are men with the
average age between 45 and 65 years old (Bypass surgery, 2015). CABG patients experience
both visceral and somatic pain from multiple incision sites (Upadya et al, 2015). This postoperative pain and/or sedation resulting from medications for pain control can delay recovery
and increase length of stay. Despite recent research supporting the use of IV acetaminophen for
postoperative pain in various surgeries, many hospitals have not adopted this practice for
postoperative CABG patients. Evidence of the effectiveness of IV acetaminophen in the cardiac
surgical patient could generate positive results, including increased alertness and mobility after
surgery, resulting in a shorter hospital stay.
Purpose
The purpose of this paper is to explore the effects of IV acetaminophen on pain control,
describe the advantages and disadvantages of IV acetaminophen compared to current
postoperative pain medications used, and discuss implications for nursing practice, education,
and research.
Methods
Using electronic databases, research articles were searched for peer-reviewed articles
published between 2010-2015. The databases searched were CINHAL and Medline. Key words
used in various combinations included cardiac, post-operative, paracetamol, acetaminophen,
heart, surgery, and pain. Inclusion criteria were the English language, adult, peer-reviewed,
postoperative surgery, and pain. Exclusion criteria were studies in pediatric populations,
newborns, and any article that did not include acetaminophen as its treatment variable. The

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search yielded an acceptable number of research articles ranging from 2001 to 2015. Fifteen
articles were chosen based on relevance in which a literature review was conducted.
Literature Review
In this systematic literature review, acetaminophen is a widely reported drug used in the
postoperative surgical patient. Although the goal was to find literature that supported
postoperative IV acetaminophen use in the cardiac surgical patient, an inadequate number of
articles were found in cardiac surgery alone. IV acetaminophen is a well-studied drug in surgical
patients, but little research exists specifically in the cardiac surgical population. Only six articles
were found that supported IV acetaminophen use in cardiac surgery while the remaining number
of articles supported its use in abdominal, orthopedic, and gynecological surgeries (See Chart I).
A retrospective cohort study by Eisenberg, Pulorak, & Bar-El (2001) studied pain after
CABG surgery. With a total sample size of 387 participants, 217 patients reported to have
chronic pain after surgery that differs from preoperative pain (Eisenberg, Pulorak, & Bar-El,
2001). Having a better control of pain during the initial postoperative period helps to gain longterm pain control (Gjeilo, Stenseth, & Klepstad, 2014). Utilizing acetaminophen during the
initial postoperative period may help relieve chronic pain (Gjeilo et al, 2014). The systematic
literature review revealed several common themes among the surgical population of which
included acetaminophen benefits, safety of acetaminophen, and decreased postoperative
complications.
Acetaminophen Benefits
Nine articles revealed adequate pain control using IV acetaminophen in the initial
postoperative setting. Three articles explored the use of IV acetaminophen in cardiac surgical
patients. Two articles studied acetaminophen use in CABG patients, and one article studied

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acetaminophen use among patients undergoing internal cardioverter defibrillator insertion. Fard,
Babaee, Alavi, Nasiri, Ghoresishi, Noori, and Mahjoubifard compared IV remifentanil with IV
acetaminophen (Fard et al, 2014). Fard et al found that the study group receiving IV
acetaminophen had better pain control than the group receiving patient controlled remifentanil
(Fard et al, 2014). However, Khaled (2015) studied the effects of giving IV acetaminophen
preventively to CABG patients but found no statistical significance in pain control using IV
acetaminophen when compared to normal saline placebo (Khaled, 2015). Khalil, Ebade, and
Azeem (2012) studied the use of IV acetaminophen during internal cardioverter defibrillator
placement. This study found statistical significance in pain control with IV acetaminophen
compared to IV fentanyl (Khalil et al, 2012).
Three articles studied the use of IV acetaminophen in abdominal surgery patients, all with
favorable results. Gonzalez, Romero, Ojeda-Vaz, and Rabaza (2014) studied the use of IV
acetaminophen in bariatric surgeries. Gonzalez et al found that the study group who received IV
acetaminophen had less opioid consumption when compared to the control group (Gonzalez et
al, 2014). Wininger, Miller, Minkoqitz, Royal, and Ang (2010) studied various dosages of IV
acetaminophen in patients undergoing abdominal surgery. Both regimens of IV acetaminophen
given in 1000mg and 650mg showed statistical significance with pain control as opposed to the
placebo group (Wininger et al, 2010). Upadya, Pushpavathi, and Seetharam (2015) compared IV
acetaminophen with intra-peritoneal bupivacaine during laparoscopic cholecystectomy. IV
acetaminophen showed the greatest pain control during the 24th postoperative hour. Intraperitoneal bupivacaine provided pain control in the early postoperative period, but IV
acetaminophen offered sustained relief (Upadya et al, 2015).

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Three articles examined the use of IV acetaminophen and its effects on pain control for
various surgeries. Khalili, Janghorbani, Saryazdi, and Emaminejad (2013) studied using IV
acetaminophen as preventative therapy during lower extremity surgery. There was statistical
significance at the sixth postoperative hour in the treatment group. There was an increase in the
pain scale at the 12th hour, but there was no increase in pain in the control group. All groups
received rescue meperidine. This study suggested that acetaminophen might decrease analgesic
consumption (Khalili et al, 2013). Apfel, Souza, Portillo, Dalal, and Bergese (2014) reviewed
five randomized, controlled studies that used IV acetaminophen in the treatment group and a
placebo in the control group. All five studies of various surgeries including abdominal,
orthopedic, and gynecological surgery found statistical significance in the treatment group with
patient satisfaction scored as excellent (Apfel et al, 2014). Macario and Royal (2010) performed
a literature review on IV acetaminophen clinical trials. This study reviewed sixteen articles of
various surgeries including abdominal, back, and cardiac surgeries. Macario and Royal found
significant reduction in opioid use, less patients using rescue medications, and longer time to
rescue medication use with IV acetaminophen (Macario and Royal, 2010).
Safety of Acetaminophen
There are many concerns with acetaminophen use including liver toxicity and overdose;
however, studies have demonstrated it is safe to use. Ahlers, Gulik, Dongen, Bruins, Tibboel, and
Knibbe (2011) studied aminotransferase levels in patients receiving four grams of acetaminophen
daily after cardiac surgery. The results of the study showed minimum increase in
aminotransferase levels suggesting the possibility of liver damage is low (Ahlers et al, 2011).
Needleman (2013) studied the infusion rates of acetaminophen. A sample size of 100
patients received a rapid infusion of IV acetaminophen and was observed for IV complications or

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pain. No adverse effects resulted from rapid administration of IV acetaminophen (Needleman,

2013).
Decreased Postoperative Complications
Acetaminophen postoperatively causes less side effects and complications when
compared to narcotics. Five articles examined postoperative complications, all with favorable
results. Shah, Jaishree, and Bhavar (2013) studied a combination medication approach using IV
tramadol and acetaminophen compared to oral tapentadol and thoracic epidural analgesia in
patients undergoing CABG surgery. The patients receiving IV tramadol and acetaminophen had a
decreased hospital length of stay, quicker time to mobilization, and quicker chest drainage
removal than the other group. Side effects increased in patients receiving oral tapentadol and
thoracic epidural analgesia including nausea and tachycardia (Shah et al, 2013).
Memis, Inal, Kavalci, Sezer, and Sut (2010) studied the use of IV acetaminophen and IV
meperidine as related to postoperative complications in a sample size of 40 patients. One group
received IV meperidine alone and the other group received IV meperidine with IV
acetaminophen. Patients who received both IV meperidine and IV acetaminophen had a quicker
extubation time and less postoperative nausea and vomiting (Memis et al, 2010).
Billings, Petracek, Roberts and Pretorius (2015) studied IV acetaminophen and its effects
on oxidant injury on patients undergoing CABG. The patients who received IV acetaminophen
had a shorter hospital length of stay. The group who received the placebo was more likely to
receive red blood cell or platelet transfusions during the operation. Billings et al found that the
acetaminophen group had reduced serum isofurans, which is an indicator of oxidative damage
that leads to acute kidney injury (Billings et al, 2015).

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Khalil, Ebade, and Azeem (2012) studied the use of IV acetaminophen and its effect
during internal cardioverter defibrillator placement. One hundred patients were randomly
assigned to one of two groups. One group received fentanyl, and the other group received IV
acetaminophen. The researchers found that the patients who received fentanyl as opposed to
acetaminophen showed airway obstruction and hypoventilation while no complications were
shown in the acetaminophen group (Khalil et al, 2012).
Literature Critique
Gaps
There was little research found for IV acetaminophen use in CABG surgery during the
last five years. Since the FDA did not approve IV acetaminophen until 2010, it has not been a
well-researched topic. There are several articles that focused on multi-modal medication use, but
no specific combination of medications was identified that offered adequate pain control for
CABG patients.
Limitations
Several limitations existed during this literature review. Performing a systematic
literature review alone can be challenging with the use of online electronic databases. Each study
used different scales to rate pain, nausea, and patient satisfaction. Not having one consistent
rating scale made it challenging to compare results from the studies and accurately report
findings.
Strengths/Weaknesses
Strengths and weaknesses were both identified in this literature review. Due to the
various types of surgeries, it was difficult to make comparisons that extended from one surgery

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to the other. Six of the fifteen studies stated that a larger sample size was needed and further
studies should be conducted.
Known/Not Known
There are many benefits to using acetaminophen for patients after surgery.
Acetaminophen provides sustained pain relief while narcotics help control acute pain (Upadya et
al, 2015). There are less postoperative complications when using acetaminophen compared to
narcotics. Acetaminophen was found to decrease nausea and vomiting (Memis et al, 2010),
decrease hospital length of stay (Shah et al, 2013), quicken extubation time due to less airway
obstruction (Memis et al, 2010) (Khalil et al, 2012), quicken mobilization after surgery (Shah et
al, 2013), accelerate removal of chest drainage tubes (Shah et al, 2013), and decrease oxidative
stress that leads to acute renal failure (Billings et al, 2015). Patients have an overall shorter
hospital length of stay that benefits patient cost (Shah et al, 2013).
Acetaminophens maximum benefit is seen when used with other narcotics. This
approach helps to decrease narcotic use (Khalil, 2012) (Macario & Royal, 2010) (Gonzalez et al,
2014). The more accurate combination of acetaminophen and narcotics to provide sustained pain
relief with the least amount of side effects is unknown.
Implications for Nursing Education/Practice/Research
Education
Acetaminophen is a non-opioid medication that helps to provide sustained pain relief
(Upadya et al, 2015). Acetaminophen use provides decreased postoperative complications when
compared to narcotics (Memis et al, 2010) (Shah et al, 2013) (Khalil et al, 2012) (Billings et al,
2015). The education curriculum for registered nurses and advanced practice nurses should
include the benefits of acetaminophen and the safety of its use for postoperative pain.

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Practice
The information obtained from the literature review can be used for prescribing pain
medications in practice. The use of IV acetaminophen in postoperative pain control can be
beneficial to hospitals as well as patients. IV acetaminophen is a cost-effective drug in that it
reduces narcotic use and improves patient safety (Shah et al, 2013). Patients are mobile more
quickly after surgery (Shah et al, 2013). Mobility alone decreases hospital length of stay by
preventing complications such as pulmonary embolism, pneumonia, and pressure ulcers (Fard et
al, 2014).
Research
Further research for CABG surgical population should include more robust sample sizes.
Further research should also include using the multi-modal approach with acetaminophen to
achieve pain control.
In summary, acetaminophen, when compared to epidural analgesia and narcotics such as
tapentadol and fentanyl, offers sustained pain relief and decreased postoperative complications
(Fard et al, 2014) (Upadya et al, 2015) (Shah et al, 2013) (Khalil et al, 2012). Acetaminophen
may help to shorten hospital length of stay and provide cost-effective pain relief (Shah et al,
2013).

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References

Ahlers, S., Gulik, L, Dongen, E. Bruins, P. Tibboel, Dl, & Knibbe, C. (2011). Aminotransferase
levels in relation to short-term use of acetaminophen four grams daily in postoperative
cardiothoracic patients in the intensive care unit. Anesthesia Intensive Care, 39(1), 10561063.
Apfel, C., Souza, Kl, Portillo, J., Dalal, P., & Bergese, S. (2014). Patient satisfaction with
intravenous acetaminophen: A pooled analysis of five randomized, placebo-controlled
studies in the acute postoperative setting. Jounral of Healthcare Quality 00(0), 1-7.
Argoff, C. E. (2013). Recent management advances in acute postoperative pain. Pain Practice,
14(5), 477-487.
Baley, K., Michalov, K., Kossick, M. A., & McDowell, M. (2014). Intravenous acetaminophen
and intravenous ketorolac for management of pediatric surgical pain: A literature review.
AANA Journal, 82(1), 53-64.
Billings, F., Petracek, M. Roberts, J, & Pretorius, M. (2015). Perioperative intravenous
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Bypass surgery in women (2015). Cleveland Clinic. Retrieved July 2, 2015 from
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Coronary artery bypass grafting: CABG (2014). University of Michigan Health System.
Retrieved July 2, 2015 from www.med.umich.edu/cardiacsurgery/patient/adult/adultcandt/cabg.shtml

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Eisenberg, E., Pultorak, Y., Pud, D., & Bar-El, Y. (2001). Prevalence and characteristics of post
coronary artery bypass graft surgery pain (PCP). Pain, 92(1-2), 11-17.
Fard, Al, Babaee, T., Alavi, S., Nasiri, A., Ghoreishi, S. Noori, N., & Mahjoubifard, M. (2014).
Intravenous patient-controlled remifentanil versus paracetamol in post-operative pain
management in patients undergoing coronary artery bypass graft surgery. Anesthesia
Pain Medication, 4(5), 1-6.
Gjeilo, K, Stenseth, R., & Klepstad, P. (2014). Risk factors and early pharmacological
interventions to prevent chronic postsurgical pain following cardiac surgery. Am J
Cardiovascular Drugs, 14(1), 335-342.
Gonzalez, A., Romero, R., Ojeda-Vaz, M., & Rabaza, J. (2014). Intravenous acetaminophen in
bariatric surgery: Effects on opioid requirements. Journal of Surgical Research, 1(95),
99-104.
Khaled, A. (2015). Preemptive parenteral paracetamol analgesia in off-pump coronary artery
bpass graft. Ain-Shams Journal of Anaesthesiology, 8(1), 21.
Khalil, M. (2012). The role of intravenous paracetamol in conscious sedation during internal
cardioverter defibrillator insertion in geriatric patients. Egyptian Journal of Anaesthesia,
29(1), 41-45.
Khalili, G., Janghorbani, M., Saryazdi, H., & Emaminejad, A. (2013). Effect of preemptive and
preventative acetaminophen on postoperative pain score: A randomized, double-blind
trial of patients undergoing lower extremity surgery. Journal of Clinical Anesthesia,
25(3), 188-192.

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Marcario, A. & Royal, M. A. (2010). A literature review of randomized clinical trials of

intravenous acetaminophen (paracetamol) for acute postoperative pain. Pain Practice
11(3), 290-296.
Memis, D., Inal, M., Kavalci, G., Sezer, A., & Sut, N. (2010). Intravenous paracetamol reduced
the use of opioids, extubation time, and opioid-related adverse effects after major surgery
in intensive care unit. Journal of Critical Care, 25(3), 458-462.
Needleman, S. (2013). Safety of rapid intravenous infusion of acetaminophen. Baylor University
Medical Center Proceedings, 26(3), 235-238.
Raffa, R. B., Pergolizzi, J. V., Taylor, R., Decker, J. F., & Patrick, J.T. (2013). Acetaminophen
(paracetamol) oral absorption and clinical influences. Pain Practice, 14(7), 668-677.
Shah, H., Jaishree, S., & Bhavsar, M. (2013). A comparative study of oral tapentadol with
thoracic epidural analgesia versus intravenous tramadol and paracetamol combination for
postoperative analgesia in off pump CABG. International Journal of Basic & Clinical
Pharmacology, 2(7), 723-727.
Upadya, M., Pushpavathi, S. H., & Seetharam, K. R. (2015). Comparison of intra-peritoneal
bupivacaine and intravenous paracetamol for postoperative pain relief after laparoscopic
cholecystectomy. Anesthesia: Essays and Researches 9(1), 39-43.
Wininger, S., Miller, H., Minkoqitz, H., Royal, M., & Ang, R. (2010). A randomized, doubleblind, placebo-controlled, multicenter, repeat-dose study of two intravenous
acetaminophen dosing regimens for the treatment of pain after abdominal laparoscopic
surgery: Original research. Clinical Therapeutics, 32(14), 2348-2369.

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Chart I

Types of Surgeries

Abdominal

Cardiac

Lower Extremity

Various

Bariatric