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Title of Guideline (must include the word Guideline (not

protocol, policy, procedure etc) Guideline for the use of naloxone in


Contact Name and Job Title (author) Dr Mark Simmonds

Consultant Critical Care Medicine
Elizabeth Jamieson Advanced Pharmacist
Practitioner Adult Critical Care
Directorate & Speciality Speciality Support (Critical Care)
Date of submission May 2015
Original guideline approved February 2012
Date on which guideline must be reviewed (this should be one to
three years) May 2018
Explicit definition of patient group to which it applies (e.g. All patients over 16 years old:
inclusion and exclusion criteria, diagnosis) - with suspected intentional opioid overdose
- in the event of unintentional respiratory
depression and reduced conscious level caused
by opioids.
Abstract This guideline describes the use of Naloxone
boluses and infusions within the clinical context
of opioid overdose. Guidance is also given
regarding the timing and level of observation and
Key Words Naloxone, opioid, overdose,
Statement of the evidence base of the guideline Evidence 3
base: (1-5)
1a meta analysis of randomised controlled trials
1b at least one randomised controlled trial
2a at least one well-designed controlled study without randomisation
2b at least one other type of well-designed quasi-experimental study
3 well designed non-experimental descriptive studies (ie comparative
/ correlation and case studies)
4 expert committee reports or opinions and / or clinical experiences of
respected authorities
5 recommended best practise based on the clinical experience of the
guideline developer
Consultation Process NUH Drugs and Therapeutics Committee
David Selwyn (HoS Critical Care)
Anette Freyer (Acute Medicine)
Fiona Branch (Critical Care)
Eleanor Crimp (Critical Care Pharmacist)
Gemma George (ED Pharmacist)
Navin Bedi (Consultant ED)
Charlotte Bebb (Renal Consultant)
For update Dr Keith Girling (Trust medical director)
Target audience
All Nursing, Medical and Pharmacy staff

This guideline has been registered with the trust. However,

clinical guidelines are guidelines only. The interpretation
and application of clinical guidelines will remain the
responsibility of the individual clinician. If in doubt contact a
senior colleague or expert. Caution is advised when using
guidelines after the review date.

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Guideline for the use of Naloxone in adult patients


Naloxone is a competitive antagonist to opioid drugs and is used in the

treatment of opioid overdose. Its duration of action is shorter than most
opioid drugs, so close patient monitoring and repeat doses or an infusion
may be required to maintain clinical effect.
Naloxone will immediately reverse opioid induced respiratory
depression. However, it will also antagonise the analgesic effect.

Initial clinical management for suspected opioid overdose or

1.1 Call Doctor to assess patient IMMEDIATELY
if there is a:
Depressed level of consciousness Neuro AVPU (alert, voice , pain,
unresponsive <A) , or
Respiratory Rate (Respiratory Rate (RR) 8 bpm).

If occurring outside the Emergency or Critical care department the Critical

Care Outreach Team (CCOT) MUST also be called

1.2 Commence Oxygen

High flow oxygen (15 litres) immediately

1.3 Review Patients Medication

All opioid medications (including opioid containing epidural infusions, and
transdermal patches) should be ceased /removed immediately

1.4 Monitor Patient

Once opioid overdose has been identified, patients should have:
Respiratory Rate and Conscious Level (AVPU)
recorded every 15 minutes.

Early Warning Scores (EWS)

calculated every 30 minutes.

1.5 Administer Naloxone:

Immediately, once the diagnosis of opioid induced severe respiratory
depression/ arrest is made.
Naloxone is stock on all wards and departments where opioid drugs are used in
the White Anaphylaxis and Over-sedation boxes. A patient safety incident
form MUST be completed following Naloxone administration.
See Quick reference guide in the box on ward or page 3 & 4 for initial doses
Intravenous access should be gained as soon as possible but if delayed,
Initial Bolus Doses:
intramuscular or subcutaneous doses may be given. The onset of action may be
slower via these routes

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TWO Indications:

1. Reversal of respiratory depression and reduced

conscious level from medicinal use of opioids (including
post-operative use), patients receiving palliative care or
are long-term (chronic) opioid users for pain control.

Naloxone initially 100-200 micrograms (1.5micrograms-3micrograms/kg)

as a slow IV bolus over 30 seconds with 100 micrograms repeated every
2 minutes until a satisfactory rise in respiratory rate is achieved.

Prepared as 400micrograms diluted to 4ml with sodium chloride 0.9%

and administered in 1ml (100microgram) aliquots.

The dose should be titrated against the respiratory function and not the
level of consciousness. Where possible the aim is to maintain adequate

If no IV access then naloxone 100-200 microgram boluses can be given

intramuscularly or subcutaneously whilst IV access is obtained

Treatment may be initiated by nursing staff in accordance with the trust

wide Patient Group Direction (PGD/TW/14) for Naloxone prior to the
arrival of medical staff.

Caution: Use of Naloxone where it is not indicated, or in larger than

these recommended doses, can cause a rapid reversal of analgesia,
leading to intense pain, distress and an increase in sympathetic nervous
stimulation / cytokine release precipitating acute opioid withdrawal
syndrome. (See Appendix 1 and adverse effects page 6)

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2. Deliberate acute opioid overdose or recreational

Naloxone 400micrograms as a slow IV bolus over 30 seconds.

If a response is seen to this initial dose then repeat 400 micrograms

every 1-2 minutes until satisfactory respiratory rate and conscious level
obtained. Each repeated dose may be given incrementally.

If NO response is seen to the first dose after 60 seconds give a dose of

800 micrograms, if still NO response after a further 60 seconds repeat
the dose of 800 micrograms. If still NO response give 2mg (larger doses
of 4 mg maybe required in seriously poisoned patients.)

If no response to total of 4mg naloxone then the diagnosis of opioid

toxicity should be questioned.

The dose maybe given undiluted or further diluted to 10ml with sodium
chloride 0.9%

If no IV access then naloxone 400microgram boluses can be given

intramuscularly or subcutaneously whilst IV access if obtained.

Caution: The aim is to AVOID completely reversing the effects in an

opioid dependent person, as this is likely to precipitate acute withdrawal


In the event of adequate clinical response to naloxone (aim for RR>10

bpm, AVPU=A), observations every 15 minutes should be maintained for
2 hours. Hourly EWS should be calculated for at least 6 hours after the
last dose of naloxone for immediate release preparations, 12 hours for
sustained release preparations and for up to 24 hours with methadone.
This maybe continued longer at the discretion of the medical team.

In the event of further deterioration, further boluses of naloxone at

previously therapeutic doses should be given and close patient
monitoring continued.
If 3 repeat boluses of naloxone are required to maintain clinical effect,
transfer to a critical care area (Critical Care, City Campus or D56 MHDU
or Critical Care C or E Floor, QMC Campus) should occur. A doctor

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and/or CCOT nurse should remain with the patient until the patient
arrives on critical care and is handed over to the critical care team.

Note: Patients receiving haemodialysis on Carrel Ward who require a

naloxone infusion should be discussed with Critical Care and referred to
CCOT but, if deemed appropriate, may remain on Carrel Ward for
ongoing renal replacement therapy.

Naloxone Infusion

An IV naloxone infusion may be useful where repeated IV doses are

required; particularly if patients have taken opioids with a long duration
of action (e.g. methadone, buprenorphine, or sustained release
preparations- Morphine M/R(e.g.Zomorph) or Oxycodone MR (e.g.Longtec)).

Naloxone infusions MUST NOT ideally be started or run outside of a

Critical Care area, Emergency Department area 1 or Carrel Ward.
If it becomes clinically necessary to start a Naloxone infusion whilst
awaiting patient transfer the CCOT nurse MUST stay with the patient to
monitor them. Naloxone to make the infusion should be obtained from
Critical Care on both campuses, D56 medical HDU or E12 Surgical
HDU, Cardiac Critical Care, ED or the pharmacy department.

Infusion regimen
Infusion preparation

Naloxone 4mg (10 x 400 micrograms) made up to

20ml with Dextrose 5% or Sodium Chloride 0.9%
(resulting solution 200 micrograms per ml).
The infusion must be administered through an electronic rate controlled
device (e.g. syringe pump). Preferably via a central venous catheter (or
large peripheral vein) to avoid potential venous irritation due to the
preparations low pH.

The initial hourly starting rate should equal 0.6 x resuscitative

cumulative bolus dose (60%) that gave an adequate clinical response.
(see table1) This should then be adjusted according to clinical condition.
The resuscitative dose is described as that dose that was sufficient to
maintain the patient with satisfactory ventilation for at least 15 minutes.
NB ~: patients may have received doses from EMAS or via the patient
held Naloxone scheme, which may need to be taken into account

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Table 1

Initial cumulative Initial hourly rate of Rate to set pump

bolus dose naloxone likely to be (4mg in 20ml
producing response necessary concentration)
400 micrograms 240 micrograms/hr 1.2 ml/hr
600 micrograms 360 micrograms/hr 1.8 ml/hr
800 micrograms 480 micrograms/hr 2.4 ml/hr
1000micrograms 600 micrograms/hr 3.0 ml/hr
1200 micrograms 720 micrograms/hr 3.6 ml/hr
1400 micrograms 840 micrograms/hr 4.2 ml/hr
1600 micrograms 960 micrograms/hr 4.8 ml/hr
1800 micrograms 1080 micrograms/hr 5.4 ml/hr
2000 micrograms 1200 micrograms/hr 6 ml/hr
Further bolus doses may be required whilst titrating the infusion; in this
case. Half the initial bolus dose should be given at 15 minutes into the

e.g: Initial cumulative bolus producing response was

naloxone 800 micrograms

Infusion is now set up and running at 2.4mls per hour

Response is not satisfactory after 15minutes

Another bolus does of 400micrograms should be given

Review with medical staff after 4 hours, or prior to preparing a new

infusion to determine if the infusion is still required.

Adverse Effects / Symptoms of Withdrawal

Abrupt reversal of opioid drugs in the context of chronic use has been
reported to precipitate acute withdrawal syndrome with symptoms of
restlessness, severe agitation, delirium, nausea and vomiting, sweating,
shivering, abdominal pain, tachycardia, hypertension and tachypnoea.
Rarely pulmonary oedema (usually in patients with pre-existing cardiac
disease), arrhythmias and cardiac arrest have been reported.
The possibility of pulmonary oedema should be considered particularly if
there is unexpected breathlessness and hypoxia after naloxone.

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Key References

Electronic British National Formulary 69
#_hit. Accessed 8th April 2015

Naloxone SPC 112th Nov 2014 (Hameln pharmaceuticals). Downloaded

from (accessed 28th January 2015)

Clarke S, Dargan P, Jones A. Naloxone in Opioid Poisoning: Walking

the Tightrope. EMJ 2005 22:612-16

Injectable Medicines Guide accessed via on

28th January 2015

University College London Hospitals 2010. Injectable medicines

administration guide 3rd Edition

Products/Naloxone-antidote/ accessed 8th April 2015

Trust-wide Patient Group Direction. Administration of Naloxone by

registered nurses to adult patients. Feb 2015. (PGD /TW14)
Nottingham University Hospitals NHS trust.

Risk of distress and death from inappropriate doses of naloxone in

patients on long term opioid/opiate treatment .NHS England
20/11/2014 (Appendix 1 page 8)

UK Medicines Information (UKMI). What naloxone doses should be used

in adults to reverse urgently the effects of opioids or opiates? April 2015:
1-19. Available at

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Appendix 1:

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