Clinical Practice

A review of ketorolac as a
prehospital analgesic
Dr Tom Edward Mallinson, Critical Care Paramedic and Mountain Rescue & Primary Care Physician, Western Isles Hospital,
Isle of Lewis, Scotland. E-mail for correspondence: [email protected]

(MHRA) (2007) has advised that treatment with

Abstract ketorolac should only be initiated in hospitals.
Non-steroidal anti-inflammatory drugs (NSAIDs) can be used as part of a However, this advice was not meant to specifically
multimodal approach to managing acute pain. Administering NSAIDs by exclude its use in the prehospital setting for a
intramuscular (IM) or intravenous (IV) injection allows them to be used in patients patient en route to hospital. It was concluded
who are nil-by-mouth, who cannot swallow, and to allow a more rapid onset by MHRA Pharmacovigilance Service that owing
compared to the oral route. Current paramedic practice in the UK does not to the relatively slow onset of action, ketorolac
generally allow for the use of an NSAID given by IM or IV injection for acute was less suitable for general prehospital use
pain. While paramedics may administer paracetamol and morphine intravenously, (Penny [MHRA Pharmacovigilance Service Team
the only option for an NSAID is oral ibuprofen, or rarely oral naproxen or rectal Manager], personal communication). In relation
diclofenac. Ketorolac is an NSAID, which can be administered by IV or IM injection. to current prehospital practice, the addition of
It is an effective analgesic agent when used alone, or in conjunction with other ketorolac to prehospital care guidelines would
agents as part of a multimodal approach to analgesia. This article reviews the provide paramedics with an intravenous (IV) or
evidence from peer-reviewed papers and current clinical guidelines surrounding the intramuscular (IM) NSAID. This would provide
safety and efficacy of ketorolac as an analgesic agent for acute pain, and discusses various prehospital analgesic options acting at
its potential use in UK paramedic practice. various points of the pain pathway, facilitating the
provision of effective multimodal analgesia.
Key words
l Ketorolac l NSAID l Non-steroidal l Analgesia l Pain Pharmacology
Ketorolac is an NSAID, which has its action
Accepted for publication 20 November 2017 through the inhibition of prostaglandin synthesis.
As an NSAID, ketorolac inhibits the action
of the cyclooxygenase enzymes (COX-1 and
COX-2), which metabolise arachidonic acid to

K etorolac was developed by the company

Syntex, which gained Food and Drug
Administration (FDA) approval for the
drug, under the trade name Toradol, in November
1989 (Gupta and Devaraj, 2013; Stolberg, 2016).
prostaglandins and thromboxane A2. NSAIDs are
therefore considered to be highly effective for
prostaglandin-mediated pathologies causing pain
and inflammation including trauma (Curtis and
Morrell, 2006; Bartkus, 2011; Gadsden, 2012).
Ketorolac was the first injectable non-steroidal anti- Ketorolac has also been shown both clinically
inflammatory drug (NSAID) to gain FDA approval, and in vitro to inhibit stretch-induced ureteral
with oral, ophthalmic and nasal preparations being contractility associated with renal colic when
approved in 1991, 1992 and 2010 respectively passing kidney stones, making it particularly useful
(Gupta and Devaraj, 2013). for colicky pain (Wood et al, 2000; Wen et al,
In the UK, ketorolac is licensed for the short- 2008). Ketorolac can be administered by various
term management of moderate-to-severe acute routes, but the IM and IV routes are most common.
© 2017 MA Healthcare Ltd

postoperative pain and, as such, its use for other These routes would produce a more rapid rise in
causes of pain would be off-label. However, this serum concentration and bioavailability compared
is not a barrier to its use, as many of the drugs to the oral route. This would be beneficial in the
used routinely in prehospital care are also being acute pain setting, and would also be useful for
used for off-label indications. The Medicine patients destined for emergency surgery who need
and Healthcare products Regulatory Agency to be kept nil by mouth.

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Speed of onset Ketorolac is widely considered one of the most

Published guidance states that the onset of action effective analgesic agents for renal and
for ketorolac can be slower than other IV analgesics, biliary colic (Wood et al, 2000; Alonso-Serra
such as morphine. It is likely that the time to and Wesley, 2003; Bledsoe and Myers, 2003).
onset is around 30 minutes with the peak effect Furthermore, it has been specifically advocated for
occurring between 45 and 60 minutes (Wood et al, use in traumatic injuries—both in the prehospital
2000; Bledsoe and Myers, 2003). This is one reason (Butler et al, 2000) and in-hospital setting
ketorolac may be considered less suitable for use in (Gadsden, 2012). In cases of colicky or traumatic
the prehospital setting. pain, ketorolac can be used as a sole agent, or
However, in regions where transport times preferably as an adjunct to other analgesia such as
to hospital are prolonged, or where there is an opiates (Bledsoe and Myers, 2003; Bartkus, 2011).
element of prolonged field care such as during In UK prehospital care, ketorolac could be used
mountain rescue operations, this is unlikely to be as the preferred first-line analgesic for patients
a valid reason to deny patients an IV or IM NSAID. with renal, ureteric and biliary colic. It could also
Furthermore, IM morphine is currently used in be a first-line treatment alongside paracetamol and
mountain rescue operations in the UK, and this morphine for traumatic limb injuries.
has demonstrated a comparable onset time to Internationally, ketorolac is commonly used
IM ketorolac (Rice et al, 1991). This suggests that during the prehospital phase to provide analgesia
ketorolac may also be useful in this area of practice. for adult patients and, in America, is considered
It may however make ketorolac a less valuable a common part of paramedics’ scope of practice
intervention in more urban ambulance services (Vincent and Williams, 2010; Beck, 2015; Phrampus
where transport times are less than 30 minutes. and Paris, 2016). Ketorolac is also used as a
battlefield analgesic by American and UK armed
Contraindications and side-effects forces (Butler et al, 2000; Shackelford et al, 2015;
Ketorolac has been favourably reviewed as having Buckenmaier and Mahoney, 2016), and its use
a better side-effect profile when compared with has been advocated in the mountain rescue and
opiates used in severe pain (Rainer et al, 2000). wilderness setting (Ellerton et al, 2014; Russell et al,
In fact, it was suggested that it may become the 2014). However, it is not currently widely used in
analgesia of choice for many emergencies ( Jelinek, UK prehospital care. Table 2 provides a summary
2000). A comparison of the common side-effects of ketorolac in the prehospital setting, and could
seen with paracetamol, NSAIDs and opiates is provide the basis for a patient group directive.
presented in Table 1.
There are a number of contraindications to the Benefits in UK prehospital care
use of ketorolac (Table 2)—many of these being Ketorolac is currently unavailable to the majority
common to all NSAIDs. Contraindications such as of UK paramedics. However, by some, it is viewed
active bleeding, increased anticoagulant and asthma as a useful analgesia adjunct when provided
are caused by the inhibition of COX, the subsequent by doctors working in prehospital care (Salkin,
antiplatelet effects, and increased leukotriene levels; 2002). Ketorolac is simple to administer, and the
as such, this would be similar with the use of any same preparation can be given intravenously or
other NSAID. It is important to note however that via the IM route. It is most commonly supplied
ketorolac does have an increased risk of causing as 1 ml of colourless (or slightly yellow) liquid of
gastrointestinal bleeding with prolonged use in 30 mg ketorolac trometamol, in an amber glass
comparison with other NSAIDs. In a prehospital ampoule. These ampoules do not need special
setting, this is unlikely to be a significant issue in
relation to a single dose. It is also important to
Table 1. Comparison of uses and side-effect profiles
remember that by using ketorolac, the expectation
would be a decreased opiate requirement and, Utility Common side effects
therefore, a reduced opiate side-effect burden. Opiates Analgesic, antidiarrhoeal Cardiovascular, respiratory and central
and antitussive activity nervous system depression
Ketorolac in clinical practice Paracetamol Analgesic and anti- Hepatotoxicity and renal impairment
Ketorolac has been demonstrated to be an effective pyretic activity in overdose
© 2017 MA Healthcare Ltd

analgesic in various circumstances. Some examples

include the following: NSAIDs Analgesic, anti- Dose dependent hepatic and renal
llRenal colic (Wood et al, 2000) inflammatory and anti- impairment
llSpinal surgery (Munro et al, 2002) pyretic activity
Bronchospasm in ~20% of asthmatics
llMigraine (Taggart et al, 2013)
llMusculoskeletal pain (Turturro et al, 1995).
Platelet inhibition

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Clinical Practice

Table 2. Drug monograph for ketorolac may be a significant advantage, such as in patients
who are immobilised, vomiting or nil by mouth.
KETOROLAC The use of ketorolac can also decrease the
Formulation Actions amount of opiates required when used as a co-
agent. This could potentially lead to fewer patients
Most commonly; a glass ampoule Ketorolac is a non-steroidal anti-
experiencing the unpleasant side-effects of high-
containing 30 mg of ketorolac in 1 ml inflammatory drug (NSAID)
dose opiates. It has also been suggested that
Its analgesic and antipyretic action is ketorolac, when used to treat pain from traumatic
through its action blocking the COX injuries may be more cost-effective than opiates
enzyme, and inhibition of prostaglandin while achieving the same level of analgesia (Rainer
synthesis et al, 2000).
Indications Side-effects
Limitations in UK prehospital care
Adult patients experiencing moderate Prolonged use can cause gastric irritation One limitation of NSAIDs is their effect of impairing
to severe pain platelet aggregation. This occurs owing to inhibition
Bronchospasm in sensitive individuals
Especially suitable for colic (renal of thromboxane A2 synthesis, as a result of COX
Nausea inhibition by ketorolac. While this antiplatelet action
colic, biliary colic, etc)
Dyspepsia has been highlighted as a reason to avoid ketorolac
Contraindications Cautions in trauma, it is likely that the anticoagulant effect is
minimal and not clinically significant (Butler et al,
Age <18 years. Previous gastric ulcer 2000). This view is supported by the meta-analysis
Concurrent use of NSAIDs or Lithium Asthma (especially in the presence of of 27 studies undertaken by Gobble et al (2014),
nasal polyps) which concluded that ketorolac provided beneficial
Ischaemic cardiac pain analgesia, and did not significantly increase
Renal impairment (see dosing below) postoperative bleeding. This antiplatelet effect is
Active gastric ulcer
Weight <50 kg (see dosing below) likely to make ketorolac less suitable in cases of
Allergy to ketorolac or its ingredients significant polytrauma—although this is not a rigid
Third trimester pregnancy or active contraindication.
labour There have been deaths linked to the use
of ketorolac, related to the risk of significant
Breastfeeding gastrointestinal bleeding with long-term use, and
Active major haemorrhage also with cases of anaphylaxis. However, the
numbers are not such that they indicate ketorolac is
Additional Information
significantly more dangerous than other commonly
Ketorolac is particularly useful for pain caused by smooth muscle spasm, and used analgesics. As with all NSAIDs, ketorolac carries
therefore works well for colicky pains a small risk of anaphylaxis (Sánchez-Borges, et
Ketorolac is also suitable for use in traumatic musculoskeletal injuries al, 2010), which can prove fatal (Oliva et al, 2007;
Campobasso et al, 2008). However, ketorolac is not
Dose and administration believed to be more allergenic than other related
Single dose only NSAIDs. It is safe to use within the limits of the
cautions and contraindications highlighted in Table 2.
The dose for ≥65 years old is also suitable for patients with; renal impairment or
Ketorolac is not currently one of the medications
weight <50 kg
authorised specifically for paramedic use in the UK,
Age (in years) Slow IV IM and it is currently a prescription-only medication
≥65 15 mg 15 mg (POM)—unlike some other NSAIDs. Therefore, for
a paramedic to use ketorolac in the UK, they would
18–<65 30 mg 30 mg need to be administering it under a Patient Group
Directive on the authorisation of a doctor (England,
2016). One of the benefits of its status as a POM,
precautions for storage, but should not be stored however, is that it is not a controlled drug (CD) and,
above 30°C or in direct sunlight. It can be given as such, is free from the restrictions surrounding
© 2017 MA Healthcare Ltd

alongside paracetamol and morphine, which are carriage and storage of CDs.
the mainstay of current paramedic pharmacological
pain management. While there appears to be no Conclusion
significant pain relief benefit in using ketorolac over Ketorolac is an effective analgesic option for IV
oral ibuprofen (Curtis and Morrell, 2006), ketorolac or IM administration. It is used in prehospital care
does allow an NSAID to be given parenterally, which internationally in both civilian and military practice.

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  Clinical Practice

TOM MALLINSON
Ketorolac is usually administered via intramuscular and intravenous routes, which can be useful in prehospital care

While there are concerns regarding its long-term use transport times may be extended; for example,
and increased risk of gastrointestinal bleeding, these owing to technical rescue or remote locations.
are unlikely to be an issue as a result of a one-off Ketorolac is a useful adjunct to the provision of
prehospital dose. Equally, many of the other cautions multimodal analgesia, and it should be considered
and contraindications for ketorolac are shared by for inclusion in the armamentarium of paramedics in
all NSAIDs and UK paramedics are already able to the UK. JPP
administer ibuprofen.
Concerns related to its variable and sometimes Conflict of Interest: None.
slow onset of action are valid and may make
ketorolac a less suitable option for use in prehospital References
© 2017 MA Healthcare Ltd

care systems where transport times are less than Alonso-Serra HM, Wesley K; National Association of EMS
Physicians Standards and Clinical Practices Committee.
an hour. Despite this, many UK paramedics work Prehospital pain management. Prehosp Emerg Care.
in a system where it takes over an hour from 2003;7(4):482-488.
patient assessment to subsequent assessment and Bartkus A. Chapter 10: Pharmacology. In: Caroline NL, Elling
management in hospital. This is especially true of B, Smith M. Nancy Caroline’s Emergency Care in the Streets.
those paramedics working where extrication and Vol 1. 7th edn. American Academy of Orthopaedic Surgeons.

Journal of Paramedic Practice • Vol 9 No 12525

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update [Internet]. Available from http://tinyurl.com/ybss2yzf

Key Points Munro HM, Walton SR, Malviya S et al. Low-dose ketorolac
improves analgesia and reduces morphine requirements
following posterior spinal fusion in adolescents. Can J
llKetorolac is an injectable NSAID analgesic Anaesth. 2002;49(5):461–466.
Oliva A, De Giorgio F, Arena V, Fucci N, Pascali VL, Navarra P.
llKetorolac is an effective analgesic when used as a sole agent, or concurrently Death due to anaphylactic shock secondary to intravenous
self-injection of Toradol: a case report and review of the
with paracetamol and morphine literature. Clin Toxicol (Phila). 2007;45(6):709-713.
Phrampus PE, Paris P. The science of pain: A guide to
llKetorolac is used worldwide in prehospital, military and wilderness settings prehospital pain management. JEMS. 2016;41(11):53-56.
Rainer TH, Jacobs P, Ng YC et al. Cost effectiveness analysis of
llThe side-effect profile of ketorolac is comparable to that of other NSAIDs intravenous ketorolac and morphine for treating pain after
limb injury: double blind randomised controlled trial. BMJ.
2000;321(7271):1247-1251.
Rice ASC, Lloyd J, Miller CG, Bullingham RE, O'Sullivan GM.
Sudbury MA: Jones and Bartlett; 2011. A double-blind study of the speed of onset of analgesia
following intramuscular administration of ketorolac
Beck RK. Pharmacology for the EMS provider. 5th edn.
tromethamine in comparison to intramuscular morphine
Philadelphia PA: F.A. Davies Company; 2015.
and placebo. Anaesth. 1991;46(7):541-544. https://doi.
Bledsoe B, Myers J. Pain & comfort: The Pathophysiology of
org/10.1111/j.1365-2044.1991.tb09651.x
pain & prehospital treatment options. JEMS. 2003;28(6):50-67.
Russell KW, Scaife CL1, Weber DC et al. Wilderness Medical
Buckenmaier C, Mahoney PF, eds. Combat Anaesthesia: the Society practice guidelines for the treatment of acute pain in
first 24 Hours. Fort Sam Houston TX: Office of the surgeon remote environments. Wilderness Environ Med. 2014;25(1):41-
General; Borden Institute; 2016. Available from http://tinyurl. 49. https://doi.org/10.1016/j.wem.2013.10.001
com/ydx763nj
Salkin B. Prehospital care for road traffic casualties.
Butler FK Jr, Hagmann JH, Richards DT. Tactical management
Doctors should offer themselves as a resource. BMJ.
of urban warfare casualties in special operations. Mil Med.
2002;325(7358):279.
2000;165(4 Suppl):1-48.
Sánchez-Borges M, Caballero-Fonseca F, Capriles-Hulett
Campobasso CP, Procacci R, Caligara M. Fatal adverse reaction
A, González-Aveledo L. Hypersensitivity Reactions to
to ketorolac tromethamine in asthmatic patient. Am J Forensic
Nonsteroidal Anti-Inflammatory Drugs: An Update.
Med Pathol. 2008;29(4):358-363. https://doi.org/10.1097/
Pharmaceuticals (Basel). 2010;3(1):10-18.
PAF.0b013e318185a00a
Curtis LA, Morrell TD. Pain Management in the emergency Shackelford SA, Fowler M, Schultz K et al. Prehospital
Department. Emerg Med Pract. 2006;8(7):1-28. pain medication use by U.S. Forces in Afghanistan.
Mil Med. 2015;180(3):304-309. https://doi.org/10.7205/
Ellerton J, Milani M, Blancher M et al. Managing moderate
MILMED-D-14-00257
and severe pain in mountain rescue. High Alt Med Biol.
2014;15(1):8-14. https://doi.org/10.1089/ham.2013.1135 Stolberg VB. Painkillers: History, Science, and Issues. Santa
Barbara CA: Greenwood [ABC-CLIO]; 2016.
England E. Paramedics and medicines: legal considerations.
J Para Pract. 2016;8(8):408-415. https://doi.org/10.12968/ Taggart E, Doran S, Kokotillo A, Campbell S, Villa-Roel C, Rowe
jpar.2016.8.8.408 BH. Ketorolac in the treatment of acute migraine: a systematic
Gadsden J. Regional anaesthesia in Trauma: A case-based review. Headache. 2013:53(2):277-287. https://doi.org/10.1111/
approach. 2012; Cambridge: Cambridge University Press. head.12009
Gobble RM, Hoang HL, Kachniarz B, Orgill DP. Ketorolac Turturro MA, Paris PM, Seaberg DC. Intramuscular ketorolac
does not increase perioperative bleeding: a meta- versus oral ibuprofen in acute musculoskeletal pain. Ann
analysis of randomized controlled trials. Plast Reconstr Emerg Med. 1995;26(2):117-120.
Surg. 2014;133(3):741-755. https://doi.org/10.1097/01. Vincent N, Williams BJ. Principles of ALS Care. American
prs.0000438459.60474.b5 Academy of Orthopaedic Surgeons. Sudbury MA: Jones and
Gupta A, Devaraj CG. 2013. Ketorolac Tromethamine in clinical Bartlett; 2010.
post operative pain management in dentistry [Internet]. Wood V, Innes G, Christenson J, Lesperance M, McKnight RD.
Available from http://tinyurl.com/y8lrq2yz Single dose intravenous ketorolac versus titrated intravenous
Jelinek GA. Ketorolac versus morphine for severe pain. Ketorolac meperidine in acute renal colic: a randomized clinical trial.
is more effective, cheaper, and has fewer side effects. BMJ. CJEM. 2000;2(2):83-89.
2000;321(7271):1236-1237. Wen CC, Coyle TL, Jerde TJ, Nakada SY. Nakada SY. Ketorolac
Medicine and Healthcare products Regulatory Agency. 2007. effectively inhibits ureteral contractility in vitro. J Endourol.
Ketoprofen and ketorolac: gastrointestinal risk. Drug Safety 2008;22(4):739-742. https://doi.org/10.1089/end.2007.9839

CPD Reflection Questions

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llIf ketorolac was introduced into UK practice, what clinical grade of practitioner do you think could safely administer it?

llWhat are the qualities of an ideal (and imaginary) analgesic agent for the prehospital care of acute pain?

llWhat other analgesic drugs do you feel would be valuable additions to paramedic practice in the UK?

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