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Volume 4 - Issue 1 2016

AEJ

Educated Hand Publishing LLC 
“The Science Behind the Art”  

 Anesthesia eJournal - Online
ISSN 2333-2611

Page 43

Effectiveness of Intravenous Acetaminophen Administration in the Postoperative Pain 
Management of the Cesarean Delivery Patient

Hazel Pickering-Luttrell, MS, CRNA
Johnny Gayden MS, CRNA
Joseph Pellegrini PhD, DNP, CRNA

Affiliations: 
University of Maryland, Baltimore School of Nursing

Conflicts/Disclosures:
 None

Keywords IV acetaminophen, paracetamol, cesarean delivery, neuraxial anesthesia, postoperative pain

INTRODUCTION
Intravenous (IV) acetaminophen has been used internationally to relieve pain in many surgical arenas. With the recent 

release of IV acetaminophen (Ofirmev; Mallinckrodt Pharmaceuticals) in the United States, many anesthetists have 
implemented using it for post-cesarean-delivery pain management, despite the lack of evidence supporting its use. An 
attractive feature supporting the use of IV acetaminophen in multimodal pain management for this population of patients is 
that it can reduce the overall side effect profile while reducing post-cesarean opioid consumption. Intravenous acetaminophen 
is typically administered as a onetime dose at the end of the surgical procedure, and research supports its use in various surgical 
procedures.1,2 What makes IV acetaminophen so attractive in the cesarean delivery patient who has received regional anesthesia 
with neuraxial opioids is the limited number of medications available to treat any breakthrough pain. Because of this, many 
practitioners began administering IV acetaminophen at the end of the cesarean delivery in an effort to reduce breakthrough 
pain and the need for supplemental opioids beyond those administered neuraxially. While there are many benefits for 
administration of IV acetaminophen, we should also discuss that a percentage of adult patients may have some adverse effects 
such as nausea, vomiting, insomnia, and headache. Pediatric patients are susceptible to those adverse effects with a potential 
for pruritus, constipation, agitation, and atelectasis as well.3 This article aimed to explore the efficacy of IV acetaminophen use 
in multimodal therapy to decrease overall opioid requirements in post-cesarean pain management. Our PICOT (population, 
intervention, comparison, outcome, time frame) research question thus examined the efficacy of IV acetaminophen as an 
adjunct to spinal anesthesia techniques with local anesthetics (bupivacaine and lidocaine) along with intrathecal opioids 
(fentanyl and morphine) in minimizing the incidence of rescue opioids or nonsteroidal anti-inflammatory drugs (NSAIDs) for 
postoperative pain management during the first 24 hours after cesarean delivery. The purpose of this evidenced-based literature 
review was to determine whether IV acetaminophen reduces opioid requirements in patients who have elective cesarean 
deliveries with neuraxial anesthesia.

Abstract
Intravenous (IV) acetaminophen has been used internationally as part of a multimodal approach to pain management 

for general surgeries and in some cesarean deliveries for postoperative pain management. In the case of post-cesarean 
pain management, however, little evidence supports the use of IV acetaminophen. The purpose of this evidenced-
based literature review was to determine whether IV acetaminophen reduces opioid requirements for elective cesarean 
deliveries with neuraxial anesthesia. Google Scholar, CINAHL, PubMed, Cochrane, and Medline were searched. Articles 
addressing IV acetaminophen and cesarean delivery with neuraxial anesthesia were included. Outcome measurements 
were specific for postoperative opioid requirements, pain control satisfaction, and visual analogue scores. The literature 
review resulted in 3 randomized controlled trials with a total of 225 patients, of which 112 received IV acetaminophen. 
Two studies used fentanyl, and 1 used morphine. All articles found IV acetaminophen improved outcomes; 3 articles 
suggested that IV acetaminophen in combination with a nonsteroidal anti-inflammatory drug was more effective. 
Analysis of the evidence revealed IV acetaminophen is a valuable component of multimodal therapy in the reduction 
of post-cesarean opioid requirements. On the basis of the current body of evidence, we can reasonably recommend IV 
acetaminophen for elective cesarean delivery patients using neuraxial anesthesia.



Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 4 - Issue 1 2016 Page 44

 Analysis of the literature suggests that IV acetaminophen is 
effective in reducing surgical opioid requirements. Arici et al1 
conducted a prospective randomized controlled trial to evaluate 
the effectiveness of IV acetaminophen in patients undergoing 
total hysterectomy and found that 1 g IV acetaminophen 
30 minutes before induction decreased visual analogue scale 
(VAS) scores, decreased total morphine consumption over 24 
hours, produced fewer side effects, and even decreased length 
of stay in the hospital. This study further purported that 1 g IV 
acetaminophen is comparable to 10 mg morphine.1 Remy et 
al2 conducted a meta-analysis that showed acetaminophen, oral 
or IV, reduced morphine consumption in surgical patients of 
amounts up to 10 mg (approximately 20%) in the first 24 hours. 
It is important to note that this meta-analysis did not restrict 
its population to obstetric surgery and that acetaminophen 
was administered both intravenously and orally.2 The meta-
analysis included a study by Siddik et al,4 which examined a 
small sample of elective cesarean delivery patients who received 
neuraxial anesthesia, IV propacetamol (a prodrug form of 
acetaminophen), and oral diclofenac. In this study, diclofenac 
compared to propacetamol significantly reduced morphine 
consumption postoperatively.4 Newer studies have replicated 
those results with a positive correlation in treatment with IV 
acetaminophen in conjunction with diclofenac for a decrease in 
postoperative opioid consumption.5 Additionally, Munishankar et 
al6 found that patients who received a combination of diclofenac 
and paracetamol required less morphine than did those given 
paracetamol alone. One limitation is the route of delivery for the 
medications; it was given as a suppository.6 The article failed to 
address whether diclofenac alone or paracetamol alone showed a 
significant difference. These studies were included to acknowledge 
that using a multimodal approach to pain therapy, including IV 
acetaminophen, is worthwhile. The limitations of this analysis 
include a small sample size of articles available for the literature 
search.

The present article focused on the obstetric population 
undergoing cesarean delivery with spinal anesthesia. The 
independent variable examined was IV acetaminophen 
administered after spinal anesthesia using hyperbaric bupivacaine 
or lidocaine and intrathecal opioids. Control groups included 
those who received placebo with IV opioids during the 
perioperative period. Evaluated dependent variables included 
the incidence of rescue opioids using the different objective 
scales as outlined in Appendix A. Other studies included were 
for supportive information regarding pharmacokinetics and 
pharmacodynamics.

HISTORY
 Intravenous acetaminophen recently entered the market 

in the United States with the brand name Ofirmev.3 Patients 
who are unable to take medications by mouth or who may 
have absorption issues can be given this IV formulation as an 
adjunct in multimodal therapy in the perioperative period. Many 
practitioners refrain from using IV ketorolac owing to patient 
allergies, platelet dysfunction, or renal status. However, IV 
acetaminophen may be used in place of IV ketorolac.

 Opioid administration has a dose-dependent side effect profile 
that includes nausea, vomiting, and respiratory depression that 
can delay discharge times.3 Additionally, the use of IV opioids 
is often limited in the cesarean delivery population owing to the 
concomitant administration of intrathecal opioids with a local 
anesthetic for postoperative analgesia, thereby limiting opioid 
administration within the first 24 hours following surgery.7

 Acetaminophen is a centrally acting analgesic and antipyretic; 
however, the exact mechanism of action is not completely 
understood.8,9 Some authors have proposed that acetaminophen 
inhibits the nitric oxide synthesis pathway and inhibits 
prostaglandin synthesis.10 Although other studies agree with 
the nitric oxide pathways, they also provide information about 
the possibility of inhibition of cyclooxygenase, opioidergic, 
N-methyl-D-aspartate receptor (NMDA) inhibition, 
serotonergic, and endocannabinoid systems as a mechanism 
of action.7-12 Acetaminophen dosing and administration 
considerations include hepatic first-pass metabolism and 
potential hepatic damage whether the route is oral, rectal, or IV. 
The bioavailability of medications administered affect timing 
for prescribing them in a multimodal therapy model. The 
maximum blood concentration (Cmax) of acetaminophen given 
intravenously is 29 mcg/mL, that for the oral formulation is 
14.2 mcg/mL, and that for the rectal formulation is 10.3 mcg/
mL.13 Pharmacokinetic information indicates that dosing of IV 
acetaminophen does not reach the hepatotoxic levels of 150 mcg/
mL, even with repeat dosing.14

 Kulo et al15 collected plasma or urine samples from 39 
women scheduled for elective cesarean delivery to evaluate the 
pharmacokinetics of IV paracetamol. Eight of these women 
were then enrolled again for evaluation at weeks 10 and 15 
postpartum for evaluation of clearance. According to their 
plasma concentration factors, women show a higher clearance 
of paracetamol at delivery than at 12 weeks postpartum. 
The information presented suggests that the likelihood of 
hepatotoxicity should be decreased. The article does note that 
because there is a higher clearance to potentially hepatotoxic 
oxidative metabolites at delivery, one may consider a higher 
dosing during this period. Additional research is needed to 
determine the incidence of hepatotoxicity with the current 
recommended perioperative dose of 1 gram IV acetaminophen 
in elective cesarean delivery patients.15 Moreover, hepatotoxicity 
has not been widely examined as an adverse reaction, even with a 
onetime dose.

 Multimodal therapy is accepted as common practice today 
owing to its ability to be specific and sensitive to each patient’s 
pain management requirements. However, it should also be noted 
that the cost of IV acetaminophen has more than doubled in the 
United States between 2013 and 2014. The usual cost per dose to 
the hospital at wholesale was $12 to $13 in 2013 and is now more 
than $35.3,14 Ordinarily, an increase in the price of the medication 
would translate to an increase in cost to the patient. Because 
billing is typically a whole collected fee in the elective cesarean 
delivery patient population, research studies have not evaluated 
the cost-effectiveness of IV acetaminophen in this scenario. The 
cost-effectiveness of IV acetaminophen can also be an eliminating 
factor to a hospital’s choice to carry the drug on formulary and its 
consistent use within a particular population.



Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 4 - Issue 1 2016 Page 45

REVIEW OF THE LITERATURE
 An extensive literature review was performed by using 

Google Scholar (Google Inc), CINAHL (EBSCO Health), 
PubMed (US National Library of Medicine), Cochrane Library 
(Cochrane), and MEDLINE (US National Library of Medicine) 
to evaluate the PICOT question. Keywords used in the search 
were as follows: IV acetaminophen, paracetamol, cesarean section, 
spinal anesthesia, epidural anesthesia, neuraxial anesthesia, and 
postoperative pain.

 Articles were excluded on the basis of pain medication, 
method of delivery, and year of available articles. Any article 
older than 5 years was not included in the analysis, but may have 
been included in the supportive data. A total of 3 articles met all 
inclusion criteria. All 3 were prospective randomized controlled 
studies. Three randomized controlled trials included a total of 225 
patients, 112 of whom received IV acetaminophen. All studies 
utilized neuraxial anesthesia with an adjunct of fentanyl11,12 
and morphine (Duramorph; West-Ward Pharmaceuticals)8 for 
primary pain management and a prescribed multimodal pain 
management plan. All evaluated whether IV acetaminophen 
and neuraxial anesthesia had any impact on decreasing 
postoperative opioid requirements. Two articles suggested that 
IV acetaminophen in combination with an NSAID was superior 
to IV acetaminophen alone.5,11 Evaluation of the evidence in the 
articles is noted in Appendix A; a critique of all 3 articles is noted 
in Appendix B.

 Analysis of the evidence revealed that IV acetaminophen 
is effective in reducing cesarean delivery postoperative opioid 
requirements.8,11,12 VAS scores showed a statistically significant 
reduction (P<0.05) in the side effect profile at 4 hours and 24 
hours postoperatively.8,11 The prospective randomized controlled 
trial by Atashkhoyi et al12 showed an increased time to first 
analgesic and decreased time to ambulation with decreased 
cumulative postoperative analgesic consumption than the study 
group receiving a placebo. These findings were reinforced in 
another prospective, double-blind randomized placebo-controlled 
study by Omar and Issa8 with findings showing no rescue drug 
required in the IV acetaminophen group as compared to 25% of 
the control group who required multiple doses of meperidine for 
pain control. This can be attributed to adjunct administration of 
IV acetaminophen and is thought to be directly proportionate to 
decreased overall opioid requirements.8,11,12

 Alhashemi et al11 analyzed a spinal anesthetic technique with 
8 to 10 mg of hyperbaric bupivacaine plus 10 mcg fentanyl and 
the effectiveness of IV acetaminophen compared with those of an 
oral NSAID as part of the multimodal pain management plan. 
A morphine IV patient-controlled anesthesia (PCA) device with 
settings of 2-mg bolus, 10-minute lockout, and no basal infusion 
was included for opioid requirement measurement.11 Atashkhoyi 
et al12 examined a spinal anesthetic technique with 1.5 mL of 
hyperbaric lidocaine and 15 mcg fentanyl. Spinal anesthesia was 
confirmed and then the patients were randomized into 2 groups 
of patients receiving IV acetaminophen and a placebo, 20 minutes 
before the end of the procedure. Omar and Issa8 examined 
a spinal anesthetic technique with 8 to 10 mg of hyperbaric 
bupivacaine with 0.2 mg morphine (Duramorph; West-Ward 
Pharmaceuticals). After a T4 sensory deficit was achieved, 
patients were randomly divided into 2 equal groups. One group 

received IV acetaminophen (1 g/100 mL) at the end of the 
procedure and every 6 hours for 24 hours. The second group 
received a placebo 100-mL infusion at the same time intervals.8 
Breakthrough pain, antiemetic therapy, and opioid consumption 
were measured throughout the perioperative period. A VAS for 
pain measurement ranging from 0 to 10 was utilized throughout 
the studies. Time to first analgesic rescue, ambulation time, 
antiemetic therapy, and hemodynamic changes were analyzed for 
the first 24 hours postoperatively.

DISCUSSION
 Although the studies followed a prospective design, some 

problems were noted in each. For example, in the study by 
Alhashemi et al,11 a post hoc analysis showed 160 patients were 
needed to demonstrate a statistical difference and a follow-up 
study was not done. No statistical data were available at 48 hours 
postoperatively.11 In addition, the differing routes of medication 
administration between IV acetaminophen and oral ibuprofen 
could have confounded the outcomes. In terms of the second 
study by Atashkhoyi et al,12 this research was published in a 
journal without the benefit of peer review and the authors did 
not elaborate on the study’s limitations. Despite these limitations, 
the design was sound in that it was a randomized controlled trial 
and the findings were relevant, hence the reason this study was 
chosen for review. In the final study included for critical review by 
Omar and Issa,8 it was noted that the study used a convenience 
sample of 80 subjects, which may pose a threat to external validity. 
However, the use of a convenience sample is common in obstetric 
anesthesia protocols and all of the studies were done within 
standards of practice for clinical research and used appropriate 
statistical analysis.

SUMMARY
 Postoperative pain after cesarean delivery can be severe 

for some women and even debilitating for others. Such pain 
prevents these mothers from being able to care for their newborn 
effectively. Intravenous patient-controlled analgesia can be 
associated with incorrect programming, anxiety about self-
administering narcotics, patient ignorance, and sedation with or 
without respiratory depression.7 As a result, neuraxial anesthesia 
methods using spinal applications, with the addition of opioids, 
and patient-controlled epidural analgesia are being chosen more 
often as the primary method for pain control within the first 24 
hours after delivery. These methods of pain control help prevent 
drowsiness and enable the mother to care for her baby. Research 
that evaluates the effectiveness of IV acetaminophen in the 
obstetric population is limited. In this article, we assessed only 
those studies that looked at the effect of IV acetaminophen in 
comparison with other conventional analgesics administered at 
the time of cesarean delivery. Although the literature was limited, 
we did show that IV acetaminophen was efficacious in reducing 
overall analgesic requirements and increasing postoperative 
maternal satisfaction without the adverse events associated with 
opioids or NSAIDS. A decrease in overall opioid requirements 
and an increase in patient satisfaction scores were achieved with 
IV acetaminophen.



Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 4 - Issue 1 2016 Page 46

Acknowledgments
This review was conducted in partial fulfillment of the requirements for the Master’s of Science in Nurse Anesthesia at the 

University of Maryland Baltimore. We acknowledge the UMB School of Nurse Anesthesia faculty for expert advice and guidance in 
this assignment.



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downloads/pdf/OFIRMEVPharmacyFactSheet.pdf. Updated 2014. Accessed July 18, 2016.
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5. Darvish H, Ardestani BM, Shali SM, Tajik A. Analgesic efficacy of diclofenac and paracetamol vs. meperidine in cesarean 
section. Anesth Pain Med. 2014;4(1):e9997.

6. Munishankar B, Fettes P, Moore C, McLeod G. A double-blind randomized controlled trial of paracetamol, diclofenac or 
the combination for pain relief after cesarean section. Int J Obstet Anesth. 2008;17(1):9-14. http://dx.doi.org/10.1016/j.
ijoa.2007.06.006.

7. Angle P, Walsh V. Pain relief after cesarean section. Tech Reg Anesth Pain Manage. 2001;5(1):36-40. http://dx.doi.org/10.1053/
trap.2001.22794.

8. Omar A, Issa K. Intravenous paracetamol (Perfalgan) for analgesia after cesarean section: a double blind randomized controlled 
study. Rawal Med J. 2011;36(4):269-273.

9. Jones V. Acetaminophen injection: a review of clinical information. J Pain Palliat Care Pharmacother. 2011;25(4):340-349. http://
dx.doi.org/10.3109/15360288.2011.606293.

10. Duggan S, Scott L. Intravenous paracetamol (acetaminophen): Adis drug profile. Drugs. 2009;69(1):101-113. http://dx.doi.
org/10.2165/00003495-200969010-00007.

11. Alhashemi J, Alotaibi Q, Mashaat M, et al. Obstetrical and pediatric anesthesia. Intravenous acetaminophen vs. oral 
ibuprofen in combination with morphine PCIA after cesarean delivery. Can J Anaesth. 2006;53(12):1200-1206. http://dx.doi.
org/10.1007/BF03021581.

12. Atashkhoyi S, Rasouli S, Fardiazar Z, Ghojazadeh M, Marandi P. Preventive analgesia with intravenous Paracetamol for post-
cesarean section pain control. International Journal of Women’s Health and Reproduction Sciences. 2014;2(3):131-137. http://
dx.doi.org/10.15296/ijwhr.2014.20.

13. Singla NK, Parulan C, Samson R, et al. Plasma and cerebrospinal fluid pharmacokinetic parameters after single-dose 
administration of intravenous, oral, or rectal acetaminophen. Pain Pract. 2012;12(7):523-532. http://dx.doi.org/10.1111/
j.1533-2500.2012.00556.x.

14. Lewis AN. IV Acetaminophen (Ofirmev). Pharmacy Times. http://www.pharmacytimes.com/publications/health-system-
edition/2012/jan-2012/-iv-acetaminophen-ofirmev-. Published January 25, 2012. Accessed July 18, 2016.

15. Kulo A, Peeters M, Allegaert K, et al. Pharmacokinetics of paracetamol and its metabolites in women at delivery and post-
partum. Br J Clin Pharmacol. 2012;75(3):850-860.

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Volume 4 - Issue 1 2016 Page 47

http://dx.doi.org/10.1093/bja/aei085
http://www.ofirmev.com/downloads/pdf/OFIRMEVPharmacyFactSheet.pdf
http://www.ofirmev.com/downloads/pdf/OFIRMEVPharmacyFactSheet.pdf
http://dx.doi.org/10.1097/00115550-200107000-00006
http://dx.doi.org/10.1097/00115550-200107000-00006
http://dx.doi.org/10.1016/j.ijoa.2007.06.006
http://dx.doi.org/10.1016/j.ijoa.2007.06.006
http://dx.doi.org/10.1053/trap.2001.22794
http://dx.doi.org/10.1053/trap.2001.22794
http://dx.doi.org/10.3109/15360288.2011.606293
http://dx.doi.org/10.3109/15360288.2011.606293
http://dx.doi.org/10.2165/00003495-200969010-00007
http://dx.doi.org/10.2165/00003495-200969010-00007
http://dx.doi.org/10.1007/BF03021581
http://dx.doi.org/10.1007/BF03021581
http://dx.doi.org/10.15296/ijwhr.2014.20
http://dx.doi.org/10.15296/ijwhr.2014.20
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http://dx.doi.org/10.1111/j.1533-2500.2012.00556.x
http://www.pharmacytimes.com/publications/health-system-edition/2012/jan-2012/-iv-acetaminophen-ofirmev-
http://www.pharmacytimes.com/publications/health-system-edition/2012/jan-2012/-iv-acetaminophen-ofirmev-


Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 4 - Issue 1 2016 Page 48

APPENDIX A: EVIDENCE TABLE FOR RESEARCH STUDIES
Author, year Study Objective/

Interventions or Exposures Compared
Design Sample (N) Outcomes Studied (How Measured) Results Qualitya

Alhashemi et 
al (2006)

To compare IV acetaminophen with oral ibu-
profen in combination with morphine PCIA 
after cesarean delivery with spinal anesthesia 
using hyperbaric bupivacaine and fentanyl

Randomized 
controlled trial

N=45 women ≥ 37 weeks’ gestation 
scheduled for elective cesarean deliv-
ery under spinal anesthesia, random-
ized to receive IV acetaminophen 
Q6h plus oral placebo or ibuprofen 
400 mg Q6h plus oral placebo. 1st 
dose given orally 30 min preopera-
tively

All patients received morphine PCIA 
for 48 h

Intraoperative newborn’s Apgar scores recorded at 1 and 
5 min

Postoperatively pain scores assessed Q1h X 4 h, then 
Q4h X48 h using the VAS [0 (no pain) to 10 (worst 
pain)] at rest, documenting morphine requirements along 
with PCIA attempts made and patient level of sedation

Postoperative adverse events such as nausea, vomiting, 
pruritus, respiratory depression, and oxygen desaturation

Patient satisfaction recorded [1 (extremely dissatisfied) 
to 10 (extremely satisfied)] 48 h postoperatively

VAS scores decreased similarly in both groups over time

Statistical decrease in the opioid requirement in both the IV acetaminophen and oral ibu-
profen intervention groups (=0.001)

IV acetaminophen is a reasonable alternative as an adjunct to morphine PCIA after cesare-
an delivery for patients unable to receive NSAIDS

IA

Atashkhoyi et 
al (2014)

To evaluate the analgesic effect of preventive 
(20 min prior to surgery finish) 1 g IV parac-
etamol on postoperative pain and analgesic 
consumption during the 24 h after elective 
cesarean delivery using hyperbaric lidocaine 
with fentanyl

Prospective, 
randomized, and 
double-blind 
clinical trial

100 pregnant women, ASA I-II, aged 
18-39 years, and term pregnancy 
undergoing elective cesarean delivery 
with spinal anesthesia

Patients preloaded with 10-12 mL/kg 
of Lactated Ringer’s solution

After delivery patients randomly 
block-assigned to receive one of the 
2 study solutions: 1 g IV paracetamol 
in 100 mL normal saline over 15 min 
and placebo group with normal saline 
alone, 20 min prior to the end of the 
procedure.

Time to first analgesic rescue, time of ambulation, and 
side effects (nausea, vomiting, sedation, and hemody-
namic changes) were measured using a VAS [ 0 (no pain) 
to 10 (worst pain)] in the PACU and during the first 24 h 
postoperatively

Increased time to first analgesic in the study group in the PACU (P<0.0001) and decreased 
time to ambulation (~5 h) than those in the placebo group (P<0.001)
Cumulative postoperative analgesic consumption was lower in the study group (P<0.001)
Preventive administration of 1 g IV paracetamol reduces the intensity of pain in the PACU 
and until 4 h after operation and analgesic consumption following cesarean delivery
Incidence of adverse effects did not differ significantly between 2 groups

IA

Omar & Issa 
(2011)

To evaluate the analgesic efficacy of IV 
paracetamol (Perfalgan) for pain control after 
cesarean delivery using hyperbaric bupiva-
caine with 0.2 mg of intrathecal morphine

Prospective, 
double-blind, 
randomized, 
placebo-con-
trolled study 
Experimental 
study-compar-
ative effective-
ness

Ordinal mea-
surement

Patients were randomly divided into 
2 equal groups by a table of random-
ization

80 ASA I-II women who had elective 
cesarean deliveries under spinal anes-
thesia with spinal morphine

VAS was used to evaluate pain level (0 = no pain to 10 
= worst pain) at 6, 12, and 24 hours postoperatively by a 
resident and nurse who did not know about the treatment 
protocols
Satisfaction was evaluated at 12 and 24 hours postoper-
atively (1 = very unsatisfied to 5 = very satisfied). SPSS 
version 15 was used to analyze the data. Student’s t-test, 
chi-square test, and Mann-Whitney U-test were used 
where appropriate for statistical analysis. P-value of < 
0.05 was considered statistically significant

In the IV paracetamol (group I), no patients required rescue drug compared to 25% in the 
meperidine (group II) rescue medication group who required multiple doses to control pain 
(<0.05)

Median pain scores were less in group I at 6 hours [1 (range 1-6) vs. 3 (range 1-8), P = 
0.002] at 12 hours [2 (range 0-5) vs. 3 (range 0-7), P = 0.031], and at 24 hours [1.5 (range 
0-4) vs. 3 (range 1-8), P< 0.0001], respectively

Satisfaction was comparable in both groups

IV paracetamol is an effective treatment option and can be used to reduce the requirement 
of rescue opioid drugs for pain control after cesarean delivery

IA

Abbreviations: ASA, American Society of Anesthesiologists; IV, intravenous; NSAID, nonsteroidal anti-inflammatory drug; PACU, post-anesthesia care unit; PCIA, patient-controlled intravenous analgesia; VAS, visual analogue scale.
aRating quality of study (Newhouse et al., 2007).
Level:
I: Evidence from experimental study, RCT, or meta-analysis of RCTs.
II: Evidence from quasi-experimental study.
III: Evidence obtained from a nonexperimental study, qualitative study, or meta-synthesis.
Quality Rating Scheme:
A: High – consistent results with sufficient sample, adequate control, and definitive conclusions; consistent recommendations based on extensive literature review that includes thoughtful reference to scientific literature.
B: Good – reasonably consistent results; sufficient sample, some control, with fairly definitive conclusions; reasonably consistent recommendations based on fairly comprehensive literature review that includes some reference to scientific evidence.
C: Low/major flaw – Little evidence with inconsistent results; insufficient sample size; conclusions cannot be drawn.



APPENDIX B: CRITIQUE TABLE
Author, year Study Objective/Intervention or Exposures Compared Strengths Weaknesses
Alhashemi et al (2006) To compare IV acetaminophen with oral ibuprofen in combination 

with morphine PCIA after cesarean delivery with spinal anesthesia 
using hyperbaric bupivacaine and fentanyl

-Experimental study design with randomized controlled trial
-Institutional ethics committee approval/written informed consent 
obtained
-Clearly defined inclusion and exclusion criteria
-Groups were nearly equal size (N=22; N=23)
-Measurement scale was specific and sensitive
-Two-sided alpha=0.05
-Power analysis of 90% showing appropriate sample size, low chance 
of Type II error
-ANOVA used at the allotted time course to analyze the effects of 
therapy
-Fisher’s exact test for postoperative analysis
-Number of PCIA attempts analyzed with Mann-Whitney U-test 
(ordinal measurement)
-Statistical procedures completed using SPSS software
-Evaluating alternative but equal therapy for multimodal analgesia. 
No statistical differences noted for either adjunct therapy within 48 h 
postoperative time frame
-Results, Discussion, and Limitations identified weaknesses of the 
study

-Post hoc power analysis showed 160 patients necessary to demon-
strate statistical difference
-Follow-up study not done
-Different route of administration (IV acetaminophen vs. oral ibupro-
fen) could account for lack of variance
-Limited applicability of study to patients undergoing cesarean deliv-
ery with spinal anesthesia with Duramorph
-No dose-response curves available for studied medications

Atashkhoyi et al (2014) To evaluate the analgesic effect of preventive (20 min prior to sur-
gery finish) 1 g IV paracetamol on postoperative pain and analgesic 
consumption during the 24 hours after elective cesarean delivery 
using hyperbaric lidocaine with fentanyl

-Experimental study design with double-blind randomized controlled 
trial
-Institutional ethics committee approval/written informed consent 
obtained
-Clearly defined inclusion and exclusion criteria
-Groups were equal size (N=50; N=50)
-Measurement scale was specific and sensitive
-Two-tailed alpha=0.05
-Power analysis of 80% showing appropriate sample size, low chance 
of Type II error
-Compared the efficacy of preventive administration of paracetamol 
with patients who received placebo to eliminate variables
-Provided a thorough statistical analysis in an effort to prevent a Type 
II error by analyzing the means using Student’s t-test, medians using 
Mann-Whitney U-test, counts using Fisher’s exact and X2 tests
-Statistical procedures completed using SPSS software

-Limitations of study not well discussed
-No dose-response curves available for studied medications
-Patients were not followed up with regards to chronic pain manage-
ment
- Studies did not have preoperative analgesic injection (preemptive) 
group as an example of the importance of timing the dosage of IV 
paracetamol

Omar & Issa (2011) To evaluate the analgesic efficacy of IV paracetamol (Perfalgan) for 
pain control after cesarean delivery using hyperbaric bupivacaine 
with 0.2 mg of intrathecal morphine

-Experimental study design with double- blinded randomized con-
trolled trial
-Approval from institutional ethics committee/ written informed 
consent from patients
-Appropriate inclusion and exclusion criteria
-Randomization table for data assessed using X2 test, Mann-Whitney 
U-test, and Fisher’s Exact test where appropriate (P <0.05 is signifi-
cant)
- Results showed no statistical significance for patient demographics, 
but statistical significance for amount of rescue medications needed
-Limitations of the study clearly stated

-Small sample size
-Results limited to comparison of IV paracetamol, placebo group and 
rescue medication
-Non-probability convenience sampling may pose a threat to external 
validity

 Abbreviations: IV, intravenous; PCIA, patient-controlled intravenous analgesia.

Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 4 - Issue 1 2016 Page 49


