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Publication Date: April 5, 2018

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CADTH RAPID RESPONSE REPORT: SUMMARY OF ABSTRACTS

Perioperative Use of

NSAIDs: Safety and

Guidelines

SUMMARY OF ABSTRACTS Perioperativ e use of NSAIDs 2

Authors: Casey Gray, Charlene Argaez

Cite As: Perioperativ e use of NSAIDs: saf ety and guidelines. Ottawa: CADTH; 2018 Apr. (CADTH rapid response report: summary of abstracts).

Acknowledgments:

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Research Questions

1. What is the clinical evidence regarding the safety and harms of the perioperative use of

nonsteroidal anti-inflammatory drugs (NSAIDs)?

2. What are the evidence-based guidelines regarding the perioperative use of NSAIDs?

Key Findings

Eight systematic reviews (six with meta-analyses), six randomized controlled trials, 21 non-

randomized studies, and three evidence-based guidelines were identified regarding the

perioperative use of NSAIDs.

Methods

A limited literature search was conducted on key resources including PubMed, The

Cochrane Library, University of York Centre for Reviews and Dissemination (CRD)

databases and a focused Internet search. No methodological filters were applied to limit the

retrieval by study type. The search was limited to English language documents published

between January 1, 2013 and March 21, 2018. Internet links were provided, where

available.

Selection Criteria

One reviewer screened citations and selected studies based on the inclusion criteria

presented in Table 1.

Table 1: Selection Criteria

Population Patients (all ages) undergoing surgery

Intervention Nonsteroidal anti-inflammatory drugs (NSAIDs)

Comparator Q1: No treatment with NSAIDs, standard therapy. Q2: No comparator

Outcomes Q1: Safety and harms (e.g., adverse events, anastomotic leak rate, post-operative bleeding) Q2: Evidence-based guidelines

Study Designs Health technology assessments, systematic reviews, meta-analysis, randomized controlled trials, non-

randomized studies, evidence-based guidelines


Results

Rapid Response reports are organized so that the higher quality evidence is presented first.

Therefore, health technology assessment reports, systematic reviews, and meta-analyses

are presented first. These are followed by randomized controlled trials, non-randomized

studies, and evidence-based guidelines.

Eight systematic reviews (six with meta-analyses), six randomized controlled trials, 21 non-

randomized studies, and three evidence-based guidelines were identified regarding the

perioperative use of NSAIDs. No relevant health technology assessments were identified.

Additional references of potential interest are provided in the appendix.

Overall Summary of Findings

Eight systematic reviews1-8

(six with meta-analyses),2-6,8

six randomized controlled trials ,9-13

and 21 non-randomized studies14-34

were identified regarding the perioperative use of

NSAIDs. Detailed study characteristics are provided in Table 2.

Five studies were identified regarding perioperative NSAID use and anastomotic leaks. One

systematic review showed an increased risk with non-selective NSAIDs and no increased

risk with selective NSAIDs,4 and one systematic review was inconclusive.

1 Three non-

randomized studies reported no difference in anastomotic leaks between NSAID

administration and their comparison groups.14-16

Eight studies with divergent results were identified regarding perioperative NSAID use and

bleeding. Four systematic reviews,2-3,7-8

one randomized controlled trial,13

and three non-

randomized studies18,21-22

showed no relationship between NSAID administration and

postoperative bleeding. The authors of two systematic reviews5-6

and one non-randomized

study17

observed that NSAID use was associated with postoperative bleeding.

One systematic review6 and five randomized controlled trials

9-13 showed that perioperative

NSAID use was not associated with a higher incidence of adverse events compared with

controls. Non-randomized studies reported divergent findings; seven studies20,22-23,25-26,30,32

showed NSAIDs were well tolerated, did not result in adverse events, or resulted in fewer

adverse events when compared to the comparison group, while seven studies21,24,27-29,31,33

showed that NSAIDs were associated with serious or non-serious adverse events.

Three evidence-based guidelines35-37

were identified regarding the perioperative use of

NSAIDs. In the clinical practice guidelines for enhanced recovery after colon and rectal

surgery, the American Society of Colon and Rectal Surgeons and Society of American

Gastrointestinal and Endoscopic Surgeons indicates that there is increased risk of

anastomotic leakage associated with NSAID use after surgery.35

The Institute for Clinical

Systems Improvement (ICSI) included a recommendation to discontinue the use of NSAIDs

preoperatively in their Perioperative protocol and Health care protocol.36

The National

Institute for Health and Care Excellence (NICE) guideline on prevention, detection, and

management of acute kidney injury indicated that there is increased risk of acute kidney

injury in adults with use of NSAIDs after surgery.37


Table 2: Summary of Included Studies on the Perioperative use of Nonsteroidal Anti-

Inflammatory Drugs (NSAIDs)

First Author,

Year

NSIAD(s) Type of

Surgery

Outcome(s) of

Interest

Results Authors’

Conclusions

Systematic Reviews and Meta-Analyses

Cata, 20171 NR GI cancer Anastomotic

Leaks NR The literature is not

conclusive on whether

the use of NSAIDs is

associated with

anastomotic leaks after

gastrointestinal cancer

surgery

Teerawattananon,

20172

COX-2 inhibitors (celecoxib, parecoxib, or etoricoxib)

NR Postoperative bleeding

Intraoperative blood loss

Postoperative blood loss

No increased risk of

postoperative

bleeding events,

intraoperative blood

loss, or

postoperative blood

loss

Perioperative, single

dose, or short course of

COX-2 inhibitors can be

safely used in

individuals who are

undergoing surgery

Kelley, 20163 Ibuprofen Soft tissue

plastics Postoperative

bleeding

No differences in

bleeding events

between ibuprofen

and comparator

Ibuprofen is a safe

postoperative analgesic

in patients undergoing

common plastic surgery

soft-tissue procedures

Peng, 20164 Selective and

non-selective NSAIDs

GI Anastomotic leak

Overall, NSAIDs

increased

incidence of

anastomotic leak

Non-selective

NSAIDs (but not

selective NSAIDs)

increased the

incidence of

anastomotic leak

compared with

other analgesic

control

The meta-analysis

suggested that

postoperative NSAIDs,

especially nonselective

NSAIDs, could increase

the incidence of

anastomotic leaks

Chan, 20145 Ketorolac Tonsillectomy Hemorrhage Adults, but not

children, have an

increased risk of

post-surgical

hemorrhage with

perioperative

ketorolac use

Ketorolac can be used

safely in children, but is

associated with a five-

fold increased risk of

bleeding in adults


First Author,

Year

NSIAD(s) Type of

Surgery

Outcome(s) of

Interest

Results Authors’

Conclusions

Gobble, 20146 Ketorolac NR Postoperative

bleeding

AEs

The odds of

postoperative

bleeding were

higher in the

ketorolac group

compared with the

control group

AEs did not differ

between groups

There was a lower

incidence of AEs

with low-dose

ketorolac

Postoperative bleeding

was not significantly

increased with ketorolac

when compared with

controls, and AEs were

not statistically different

between the groups

Lewis, 20137 NR Tonsillectomy

Adenotonsillec-tomy

Bleeding The use of NSAIDs

in children was not

associated with

bleeding requiring

surgical intervention

or bleeding not

requiring surgical

intervention when

compared with other

analgesics or

placebo

There is insufficient

evidence to exclude an

increased risk of

bleeding when NSAIDs

are used in pediatric

tonsillectomy

Riggin, 20138 NR Tonsillectomy Bleeding rates

Bleeding severity

The use of

NSAIDs after

tonsillectomy was

not associated

with bleeding

Use of NSAIDs in

general or in

children was not

associated with

bleeding in

general, most

severe bleeding,

secondary

hemorrhage,

readmission, or

need of

reoperation due to

bleeding

There was no

increased odds of

bleeding for

These results suggest

that NSAIDs can be

considered as a safe

method of analgesia

among children

undergoing

tonsillectomy


First Author,

Year

NSIAD(s) Type of

Surgery

Outcome(s) of

Interest

Results Authors’

Conclusions

specific NSAIDs in

adults or children

Randomized Controlled Trials

Gago, 20169 IV ibuprofen Abdominal

surgery

Orthopedic

surgery

AEs There was no

difference in AEs

between ibuprofen

and placebo groups

IV-Ibuprofen was safe

and well tolerated

The authors

concluded that 800

mg of IV-Ibuprofen

administered every 6

hours can help

manage postoperative

pain while reducing

the potential risks

associated with

morphine

consumption

Beckmann, 201510

Naproxen Arthroscopic

surgery for

femoroaceta-

bular

impingement

AEs Minor adverse

reactions did not

differ between

naproxen and

placebo

Not relevant

Hovanesian,

201511

Ketorolac Cataract

surgery

AEs Clinically significant

AEs did not differ

between ketorolac

and placebo

The authors determined

that phenylephrine

1.0%-ketorolac 0.3%

administered

intracamerally with

irrigation solution during

cataract surgery was

safe and effective for

maintaining mydriasis

during the procedure

and reducing

postoperative ocular

pain

Shi, 201512

Etoricoxib Lumbar fusion

surgery

AEs No serious AEs Suggest that etoricoxib

was effective in safely

managing the pain

during the lumbar fusion

surgery and recovery

Moss, 201413

IV-Ibuprofen Tonsillectomy AEs

Surgical blood

loss

Postoperative

No significant

differences in the

incidence of SAEs,

surgical blood loss,

Not relevant


First Author,

Year

NSIAD(s) Type of

Surgery

Outcome(s) of

Interest

Results Authors’

Conclusions

bleeding

Need for

surgical re-

exploration

incidence of

postoperative

bleeding, or a need

for surgical re-

exploration between

Ibuprofen and

placebo groups

Non-Randomized Studies

Haddad, 201714

NR Emergency

general surgery

GI AF (AF;

dehiscence/

leak, fistula, or

abscess)

GI AF rate did not

differ between

NSAID and no

NSAID

Perioperative NSAID

utilization appears to

be safe in patients

undergoing small-

bowel resection and

anastomosis

NSAID administration

should be used

cautiously in patients

with colon or rectal

anastomoses

Rushfeldt, 201615

Ketorolac

Diclofenac

Surgery

involving an

intestinal

anastomosis

Anastomotic

leak

Compared with no

medication

receivers, adjusted

(age, sex, and

propensity score)

odds of anastomotic

leak did not differ for

ketorolac

Other factors than

perioperative drugs are

crucial for risk of AL

Saleh, 201416

Ketorolac Colorectal

resection with

primary

anastomosis

Anastomotic

leak

There was no

difference between

ketorolac and no

ketorolac after

adjusting for

smoking, steroid

use, and age

There does not appear

to be a significant

association between

perioperative ketorolac

use and anastomotic

leakage after colorectal

surgery

Gao, 201817

Ketorolac Circumcision Postoperative

bleeding

Postoperative

admission

Further

medical

intervention

Patients receiving

ketorolac were

more likely to

return to the

emergency

department or

clinic for bleeding

Patients receiving

ketorolac were

more likely to have

Although a promising

analgesic, ketorolac

requires additional

investigation for safe

usage in circumcisions

due to possible

increased risk of

bleeding


First Author,

Year

NSIAD(s) Type of

Surgery

Outcome(s) of

Interest

Results Authors’

Conclusions

postoperative

sanguineous

drainage

There was no

significant

difference in the

number of patients

requiring

postoperative

admission or

further medical

intervention

Richardson,

201618

Ketorolac Neuro-surgery Radiographic

hemorrhage

Clinically

significant

bleeding

events

There was no

association

between clinically

significant

bleeding events or

radiographic

hemorrhage and

the perioperative

administration of

ketorolac

Short-term ketorolac

therapy does not appear

to be associated with an

increased risk of

bleeding documented

on postoperative

imaging in pediatric

neurosurgical patients

Abdelmageed,

201519

Ketorolac Tonsillec-tomy

with or without

adenoidec-tomy

Bleeding time

Intraoperative

blood loss

Postoperative

bleeding

incidence and

severity

Estimated

intraoperative

blood loss did not

differ between

ketorolac and

paracetamol

Bleeding time

increased

between

preoperative and

postoperative

assessments in

both groups, with

significant

postoperative

elevation in the

ketorolac group

Overall incidence

of post-

tonsillectomy

bleeding did not

differ between

ketorolac and

Pre-emptive ketorolac

infusion during pediatric

tonsillectomy provides

superior postoperative

analgesia with no effect

on intraoperative or

postoperative clinical

bleeding


First Author,

Year

NSIAD(s) Type of

Surgery

Outcome(s) of

Interest

Results Authors’

Conclusions

paracetamol

groups

Oliveri, 201420

Ketorolac Cardiac surgery GI bleeding

AEs

Ketorolac did not

differ or had

better

postoperative

outcomes than

comparators,

including: GI

bleeding, renal

failure requiring

dialysis,

perioperative,

stroke or transient

ischemic attack,

and death

Treatment with

ketorolac was not

a predictor for

adverse outcome

in this cohort

Ketorolac appears to be

well-tolerated for use

when administered

selectively after cardiac

surgery

Ying, 201821

NR Orthopedic

surgery

AKI The authors

observed a linear

relationship

frequency of NSAID

administration and

postoperative AKI

risk

The authors concluded

that perioperative

NSAID drugs was

significantly associated

with postoperative AKI

Modjahedi, 201722

Topical Cataract

surgery

Postoperative

macular

edema

NSAID use was

associated with a

lower incidence of

postoperative

macular edema in

patients without

diabetes and

diabetics without

retinopathy

NSAID use was

not associated

with a change in

the incidence of

postoperative

macular edema

among patients

with diabetic

Topical NSAIDs were

associated with a

modest reduction of

postoperative macular

edema incidence in

patients undergoing

cataract surgery;

however, this

relationship was not

seen among those

with diabetic

retinopathy

The risk for

postoperative macular

edema is low and the

number of patients

benefiting from


First Author,

Year

NSIAD(s) Type of

Surgery

Outcome(s) of

Interest

Results Authors’

Conclusions

retinopathy treatment is small

Naseem, 201723

Ketorolac Pediatric

appendectomy

LOS

Readmission

with diagnosis

of peritoneal

abscess or

other

postoperative

infection

Transabdomin

al drainage

performed

Ketorolac was

associated with a

decrease in same-

visit surgical

complications and

not associated

with readmission,

postoperative

LOS, or

postoperative

infection

Ketorolac was

associated with a

decrease in any

complication and

not associated

with readmission,

postoperative

LOS, or

postoperative

infection

Ketorolac was not associated with an increase in postoperative LOS, postoperative infection, or any-cause 30-day readmission

Ketorolac was independently associated with a lower overall rate of postoperative complications

Takahashi, 201724

Ketorolac Laparoscopic

live-donor

nephrectomy

GFR GFR at 1 year was

significantly lower

in patients who

received ketorolac

than in those who

did not

The differences in

GFR and GFR

percentage

between 2 weeks

and 1 year after

surgery was lower

with ketorolac

Urinary

albumin/creatinine

ratio 1 year after

surgery was

significantly higher

in the ketorolac

group compared to

the non-ketorolac

group

Ketorolac use was

Ketorolac appears to be

a risk factor for renal

dysfunction in the long

term after live-donor

nephrectomy


First Author,

Year

NSIAD(s) Type of

Surgery

Outcome(s) of

Interest

Results Authors’

Conclusions

an independent

risk factor for low

GFR percentage 1

year after surgery

Donohue, 201625

Ketorolac Femoral and

tibial shaft

repair with

intramedullary

rod fixation

Time to union

Average time to

union of the femur

was 147 days for

those

administered

ketorolac and 159

days for group not

administered

ketorolac

Average time to

union of the tibia

was 175 days for

ketorolac and 175

days for no-

ketorolac group

Ketorolac administered

in the first 24 hours after

fracture repair for acute

pain management does

not seem to have a

negative impact on time

to healing or incidence

of nonunion for femoral

or tibial shaft fractures

Lohisinwat, 201626

COX-2

inhibitors

Colorectal

surgery

Postoperative

complications

Median

postoperative

stay

There was no

difference in

overall

postoperative

complications

between COX-2

administration and

no COX-2

administration

Median

postoperative stay

was 1 day shorter

with COX-2

prescription

Perioperative

administration of oral

selective COX-2

inhibitors significantly

decreased intravenous

opioid consumption,

shortened time to GI

recovery and reduced

hospital stay after open

colorectal surgery

Warth, 201627

Celecoxib

Ketorolac

(when

necessary)

Primary and

revision total hip

arthroplasty and

total knee

arthroplasty

AKI NSAIDs use was

associated with a

4.8% rate of AKI,

which is 2.7 times

higher than the

reported literature

Not relevant

Behman, 201528

COX-2 and

non-selective

inhibitors

Pancreatic

duodenectomy

PF NSAID use was

not associated

with PF, or

difference in major

morbidity or

COX-2 inhibitors are

associated with PF in

the early

postoperative period

While non-selective


First Author,

Year

NSIAD(s) Type of

Surgery

Outcome(s) of

Interest

Results Authors’

Conclusions

mortality

Use of non-

selective inhibitors

was not

associated with an

increase in PF

COX-2 inhibitors

were associated

with increased PF

but no difference

in major morbidity

or mortality

Use of COX-2

inhibitors was

independently

associated with PF

inhibitors appear safe

in this setting, caution

is warranted with the

use of COX-2

inhibitors

Gan, 201529

IV-ibuprofen Not specified SAEs and non-

SAEs

~22% of patients

reported AEs,

including:

infusion site pain

Nine SAEs were

reported and were

judged unrelated

to ibuprofen

Our study found that IV

ibuprofen infused over 5

to 10 minutes at

induction of anesthesia

is a safe administration

option for surgical

patients

Lizardo, 201530

Ketorolac Video-assisted

thorascopic

surgery with

pleurodesis for

pneumothorax

LOS

Radiographic

pneumothorax

resolution prior

to discharge

Ipsilateral

recurrence

rates

There were no

differences in

average LOS,

incidence of residual

pneumothorax at

discharge, or

ipsilateral recurrence

between ketorolac

use and no ketorolac

use

Despite the intrinsic

anti-inflammatory

properties of ketorolac,

our data suggests that

its use for patients

undergoing pleurodesis

for spontaneous

pneumothorax does not

detrimentally influence

the outcomes of surgery

Jian, 201431

Flurbiprofen,

hypertension,

or HES

Craniotomy Post-

craniotomy

intracranial

hematoma

requiring

surgery

Hematoma requiring

surgery was

associated with

flurbiprofen use

during but not after

the surgery. The

intraoperative

infusion of HES

showed no

difference between

patients who had a

Intraoperative and

postoperative

hypertension and the

use of flurbiprofen

during surgery are risk

factors for post-

craniotomy

intracranial hematoma

requiring surgery

The intraoperative

infusion of HES was


First Author,

Year

NSIAD(s) Type of

Surgery

Outcome(s) of

Interest

Results Authors’

Conclusions

hematoma and

those who did not

not associated with a

higher incidence of

hematoma

STARSurg

Collaborative,

201432

NR GGI surgery Major

complications

NSAID use was

associated with a

reduction in overall

complications

This effect

predominantly

comprised a

reduction in minor

complications with

high-dose NSAIDs

Early use of NSAIDs is

associated with a

reduction in

postoperative adverse

events following major

GI surgery

Beckmann, 201433

Naproxen Hip arthroscopy AEs Complications of

NSAID use included

acute renal failure,

hematochezia from

acute colitis, and

gastritis

Side effects from the

investigated NSAID

regimen can be serious

and should be weighed

against the potential

benefits in preventing

the formation of

Heterotopic Ossification

AE = adv erse ev ent; AF = anastomotic f ailure; AKI = acute kidney injury ; COX = cy clooxy genase; GFR = glomerular f iltration rate; GI = gastrointestinal; HES =

hy droxy ethyl starch; IV = intrav enous; LOS = length of stay ; NR = not reported; NSAID = non-steroidal anti-inf lammatory ; PF = pancreatic f istula; SAEs = serious adv erse

ev ent.

References Summarized

Health Technology Assessments

No literature identified.

Systematic Reviews and Meta-analyses

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inflammatory drugs in the oncological surgical population: beneficial or harmful? A

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PubMed: PM23881651

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Randomized Controlled Trials

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34.National Guideline Clearinghouse. Guideline summary: clinical practice guidelines for

enhanced recovery after colon and rectal surgery from the American Society of Colon

and Rectal Surgeons and Society of American Gastrointestinal and Endoscopic

Surgeons. In : National Guideline Clearinghouse [Internet]. Rockville (MD): Agency for

Healthcare Research and Quality; 2017 Aug [cited 2018 Apr 5]. Available from:

https://www.guideline.gov/summaries/summary/51065/clinical-practice-guidelines-for-

enhanced-recovery-after-colon-and-rectal-surgery-from-the-american-society-of-colon-

and-rectal-surgeons-and-society-of-american-gastrointestinal-and-endoscopic-

surgeons?q=nsaid+AND+Perioperat

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care protocol. In: National Guideline Clearinghouse [Internet]. Rockville (MD): Agency

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care-protocol?q=nsaid+AND+Perioperat

See section: 2.4.2 Drugs to Stop

36.Acute kidney injury: prevention, detection and management [Internet]. London: National

Institute for Health and Care Excellence; 2013 Aug [cited 2018 Apr 5]. (NICE guideline;

no. 169). Available from: https://www.nice.org.uk/guidance/cg169/resources/acute-

kidney-injury-prevention-detection-and-management-pdf-35109700165573

See: Assessing risk factors in adults having surgery, page 11

http://www.ncbi.nlm.nih.gov/pubmed/26385568http://www.ncbi.nlm.nih.gov/pubmed/24966149http://www.ncbi.nlm.nih.gov/pubmed/25091299http://www.ncbi.nlm.nih.gov/pubmed/24664136https://www.guideline.gov/summaries/summary/51065/clinical-practice-guidelines-for-enhanced-recovery-after-colon-and-rectal-surgery-from-the-american-society-of-colon-and-rectal-surgeons-and-society-of-american-gastrointestinal-and-endoscopic-surgeons?q=nsaid+AND+Perioperathttps://www.guideline.gov/summaries/summary/51065/clinical-practice-guidelines-for-enhanced-recovery-after-colon-and-rectal-surgery-from-the-american-society-of-colon-and-rectal-surgeons-and-society-of-american-gastrointestinal-and-endoscopic-surgeons?q=nsaid+AND+Perioperathttps://www.guideline.gov/summaries/summary/51065/clinical-practice-guidelines-for-enhanced-recovery-after-colon-and-rectal-surgery-from-the-american-society-of-colon-and-rectal-surgeons-and-society-of-american-gastrointestinal-and-endoscopic-surgeons?q=nsaid+AND+Perioperathttps://www.guideline.gov/summaries/summary/51065/clinical-practice-guidelines-for-enhanced-recovery-after-colon-and-rectal-surgery-from-the-american-society-of-colon-and-rectal-surgeons-and-society-of-american-gastrointestinal-and-endoscopic-surgeons?q=nsaid+AND+Perioperathttps://www.guideline.gov/summaries/summary/48408/perioperative-protocol-health-care-protocol?q=nsaid+AND+Perioperathttps://www.guideline.gov/summaries/summary/48408/perioperative-protocol-health-care-protocol?q=nsaid+AND+Perioperathttps://www.nice.org.uk/guidance/cg169/resources/acute-kidney-injury-prevention-detection-and-management-pdf-35109700165573https://www.nice.org.uk/guidance/cg169/resources/acute-kidney-injury-prevention-detection-and-management-pdf-35109700165573


Appendix — Further Information

Previous CADTH Reports

37. Ketorolac versus non-steroidal anti-inflammatory drugs for the management of acute

pain: comparative clinical effectiveness [Internet]. Ottawa: CADTH; 2017 Jan [cited

2018 Apr 5]. (CADTH Rapid response report: summary of abstracts). Available from:

https://www.cadth.ca/sites/default/files/pdf/htis/2017/RB1055%20Toradol%20vs%20NS

AIDS%20Final.pdf

38. Non-steroidal anti-inflammatory drugs in patients with hypertension, chronic kidney

disease, or heart failure: benefits, harms, and guidelines [Internet]. Ottawa: CADTH;

2015 Mar [cited 2018 Apr 5]. (CADTH Rapid response report: summary of abstracts).

Available from: https://www.cadth.ca/sites/default/files/pdf/htis/mar-

2015/RB0809%20NSAIDs%20for%20HT%20CKD%20and%20HF%20Final.pdf

39. Ketorolac for pain management: a review of the clinical evidence [Internet]. Ottawa:

CADTH; 2014 Jun [cited 2018 Apr 5]. (CADTH Rapid response report: summary of

abstracts). Available from: https://www.cadth.ca/sites/default/files/pdf/htis/nov-

2014/RC0565%20Toradol%20Final.pdf

40. Non-steroidal anti-inflammatory drugs for pain: a review of safety [Internet]. Ottawa:

CADTH; 2013 Aug [cited 2018 Apr 5]. (CADTH Rapid response report: summary with

critical appraisal). Available from:https://www.cadth.ca/sites/default/files/pdf/htis/aug-

2013/RC0471%20NSAID%20safety%20final.pdf

Review Articles

41. Wick EC, Grant MC, Wu CL. Postoperative multimodal analgesia pain management

with nonopioid analgesics and techniques: a review. JAMA Surg. 2017 Jul 1;152(7):691-

7.

PubMed: PM28564673

Additional References

42. Scott WW, Levy M, Rickert KL, Madden CJ, Beshay JE, Sarode R. Assessment of

common nonsteroidal anti-inflammatory medications by whole blood aggregometry: a

clinical evaluation for the perioperative setting. World Neurosurg. 2014 Nov;82(5):e633-

e638.

PubMed: PM24698769
https://www.cadth.ca/sites/default/files/pdf/htis/2017/RB1055%20Toradol%20vs%20NSAIDS%20Final.pdfhttps://www.cadth.ca/sites/default/files/pdf/htis/2017/RB1055%20Toradol%20vs%20NSAIDS%20Final.pdfhttps://www.cadth.ca/sites/default/files/pdf/htis/mar-2015/RB0809%20NSAIDs%20for%20HT%20CKD%20and%20HF%20Final.pdfhttps://www.cadth.ca/sites/default/files/pdf/htis/mar-2015/RB0809%20NSAIDs%20for%20HT%20CKD%20and%20HF%20Final.pdfhttps://www.cadth.ca/sites/default/files/pdf/htis/nov-2014/RC0565%20Toradol%20Final.pdfhttps://www.cadth.ca/sites/default/files/pdf/htis/nov-2014/RC0565%20Toradol%20Final.pdfhttps://www.cadth.ca/sites/default/files/pdf/htis/aug-2013/RC0471%20NSAID%20safety%20final.pdfhttps://www.cadth.ca/sites/default/files/pdf/htis/aug-2013/RC0471%20NSAID%20safety%20final.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/28564673http://www.ncbi.nlm.nih.gov/pubmed/24698769

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