11/14/24, 10\:53 AM Opioid Overdose

Opioid Overdose

Table of contents
Key points ⚡
Succinct notes to superpower your revision
Medication overdose\: common emergency presentation; opioids most likely to cause death; 2,208 deaths in England and
Wales in 2018 due to opioids.
Opiate vs. Opioid\: Opiates are natural alkaloids (e.g. morphine, codeine); opioids are synthetic or semi-synthetic (e.g.
fentanyl, oxycodone); opioids include all drugs binding opioid receptors.
Pharmacology\: Opioid receptors (G-coupled proteins) in CNS and PNS; three main subtypes\: mu (most analgesic, euphoria,
respiratory depression), kappa (analgesia, dysphoria), delta (least understood).
Examples\:
Codeine\: oral; constipating; available with paracetamol.
Tramadol\: oral/IV; lowers seizure threshold; interacts with serotonin receptors.
Morphine\: oral/IV/SC; high street value; risk of overdose.
Fentanyl\: IV/transdermal; very potent.
Methadone\: oral; used for addiction; risk of overdose.
Heroin\: IV; most common cause of opioid overdose death.
Risk factors\:
Recreational use\: IV drug users, all administration routes.
Intentional overdose\: self-harm, suicide attempt.
Unintentional overdose\: chronic pain, elderly, children, new opioid, therapeutic error, renal/hepatic impairment, CYP2D6
gene duplication.
Clinical features\:
History\: decreased consciousness, nausea/vomiting, constipation, pruritis, somnolence, confusion.
Examination\: ABCDE approach; reduced consciousness, respiratory depression, miosis (pinpoint pupils); potential for rapid
deterioration.
Di
narcosis.
Investigations\:
Bedside\: observations, arterial blood gas, capillary blood glucose.
Bloods\: FBC, U&Es, LFTs, paracetamol levels.
Imaging\: CT head if no improvement after initial management.
Management\:
Acute\: Remove opioid source, close monitoring, ABCDE approach, airway management, naloxone administration (IV, IM, SC,
intranasal).
Naloxone use\: Repeat doses if necessary; di
cleared from the system.
Complications\:
Opioid overdose\: death due to respiratory depression, acute lung injury (similar to ARDS).
Naloxone treatment\: acute withdrawal syndrome, nausea, vomiting.
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Introduction

Medication overdose is an increasingly common presentation, particularly in the emergency department, with patients
presenting with a broad range of clinical features.
Of all drugs taken in overdose, opioids have been consistently shown to be the most likely to cause death.
1
In 2018 4,359 deaths in England and Wales were attributed to medication overdose, 2,208 of which were due to opioid
drugs (excluding paracetamol containing compounds, such as co-codamol).
1
Opioid abuse is a global problem. The World Health Organisation (WHO) estimates that 500,000 deaths worldwide are
attributed to drug use, with more than 21% of these attributed to opioid overdose. In 2017, the WHO estimates that 115,000
people died from opioid overdose.
2

Aetiology

Terminology

The terms opiate and opioid are often used interchangeably. However, they have di
An opiate is a naturally occurring alkaloid drug derived from the opium poppy (e.g. morphine and codeine).
An opioid is any synthetic or semi-synthetic drug derived from the opium poppy (e.g. fentanyl and oxycodone).
Opioid is also used as the broad term for any substance which binds opioid receptors to produce an opiate-like toxidrome.
A l l o p i a t e s a r e o p i o i d s , b u t n o t a l l o p i o i d s a r e o p i a t e s.
3

Pharmacology

Opioid receptors are G-coupled proteins. The highest concentration of opioid receptors is in the central nervous system
however some receptors exist in the peripheral nervous system.
There are three main receptor subtypes\:
Mu receptors
Kappa receptors
Delta receptors
Activation of all three receptor sub-types produces analgesic e
opioid in a medical setting.
However, the side e
pupils) and higher cortical processing e
The physiological roles (although not yet fully understood) of each receptor subtype are summarised below\:
4
Mu receptors\: this is the most abundant and best-understood receptor sub-type. These receptors have the highest
a
which is also responsible for euphoria, respiratory depression and constipation associated with opioid use.
Kappa receptors\: these receptors produce less analgesia than mu receptors. They are associated with reduced
consciousness, respiratory depression, dependence and dysphoria.
Delta receptors\: the e
thought to be involved in the psychological e

Opioid drug examples

The ‘strength’ of an opioid drug is governed by its ability to act as an agonist at the mu receptor (as these produce the
greatest analgesic e
Table 1. The main medicinal forms of opioids.
Generic name
Strength
Routes Indications Cautions
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Codeine
Weak
Oral
Useful for most types of pain
and in most patients.
Also, in a form with
paracetamol 8/500 (8mg
codeine, 500mg paracetamol)
available over the counter,
30/500 by prescription only.
Generally quite constipating.
Tramadol
Weak
Oral
IV
Useful in postoperative
analgesia for general surgery;
less constipating than other
opioid preparations and
available parenterally.
Lowers seizure threshold, therefore, avoided
in epilepsy and other seizure disorders.
Can precipitate delirium in older patients.
As well as opioid pathways, it interacts with
serotonin receptors, therefore, can cause
serotonin syndrome (usually in conjunction
with other serotonin-interacting drugs).
Unlike other weak opioids is a controlled drug
therefore extra prescription requirements.
A controlled drug which carries a high street
value.
Strong preparation, taken usually without
supervision at home therefore higher
(accidental) overdose rates.
Morphine
Strong
Oral, IV, SC
Easy to use for immediate
severe pain relief and is familiar
to most medical and nursing
sta
IV dose can be titrated to e
in the immediate setting.
Easy to titrate oral dose to
requirement.
Fentanyl
Strong
IV,
transdermal
Chronic pain treatment in patch
form, an anaesthetic agent in IV
form.
Extremely potent – prescribed in micrograms
unlike most other opioids (in milligrams).
High street value.
Potential for overdose.
Methadone
Strong
Oral
A long-acting drug used in
opioid addiction for weaning
and avoiding withdrawal.
Labour intensive for prescriber/administrator
– short term scripts, often observed taking
daily in clinics.
Heroin
Strong
IV
An illegal street drug, crude
preparation of diamorphine.
The most common cause of death in opioid
overdose.
1
This table is not an exhaustive list of available opiates. Some preparations/routes are for specialist use only, for example
fentanyl in any form.

Risk factors

There are di
Recreational drug use\:
Most commonly by intravenous drug users
Any route of opioid administration has the potential to be abused
Intentional overdose\:
Self-harm or suicide attempt
Less commonly an attempt to harm someone else in a person’s care, by purposefully administrating more than the
prescribed dose
Unintentional overdose\:
Chronic pain or palliative care patients
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Elderly, more likely if starting a new opioid, changing a dose or starting a new interacting medication
Children (safeguarding issue)
Starting a new opioid, especially in the opioid naïve
A therapeutic error by incorrect prescription or incorrect dose/form/agent administration
Hepatic or renal impairment\: opioid may not be metabolised fully or can accumulate to toxic levels
CYP2D6 gene duplication carriers causing ultra-fast metabolism of codeine into its active metabolite, morphine, into
potentially toxic concentrations
5

Clinical features

History

comatose patient.
In clinical practice, the presentation of opioid overdose is a spectrum ranging from mild symptoms to a completely
Many patients will present with a decreased level of consciousness and no speci
present these may include\:
Nausea and/or vomiting
Constipation
Pruritis
Tiredness and increased somnolence
Confusion (especially in the elderly)
Be aware these symptoms can also represent side e
opioid-sensitive and/or opioid naïve patient subgroup.
Other important areas to cover in the history include\:
Drug history\: obtain an accurate history of what opioids the patient is taking and compare this to their prescription. Be
sure to review all sources of opioid prescription. It is an easy mistake for prescribers in di
GP and a hospital doctor) to prescribe opioids without realising the other already has.
Past medical history\: assess for risk factors for unintentional overdose (e.g. renal impairment)
Psychiatric history\: previous episodes of overdose and/or self-harm.
Mixed drug overdoses
Patients often present with mixed drug overdoses. Be sure to take a thorough history and formulate a management
plan for all ingested substances. Consult local poisons information services (e.g. Toxbase) if required.
Clarify the preparation of opioid your patient has taken; some opioids come in paracetamol containing preparations,
for example, co-codamol and co-dydramol. It is imperative to investigate and treat for paracetamol overdose, due to
the risk of long-lasting and potentially fatal hepatic complications.
Unfortunately, the patient may have overdosed as an attempt to self-harm or end their life. Be sure to complete a
thorough risk assessment and mental state exam as part of your assessment.

Clinical examination

The classical clinical toxidrome of opioid overdose is a triad of\:
reduced consciousness
respiratory depression
miosis
As with all acutely unwell patients, clinical assessment should follow an ABCDE approach.
Airway
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The patient may be awake and talking with or without slurred speech, demonstrating that their airway is patent. In more
severe overdoses, because of decreased consciousness, the airway may become partially obstructed with snoring or
noisy breathing.
Partial airway obstruction can rapidly lead to complete airway obstruction and cardiorespiratory arrest. Be aware that
vomiting in a patient with a decreased level of consciousness conscious poses a potential risk to the airway.
Breathing
Respiratory depression in opioid overdose presents with bradypnoea, hypoxia and in severe cases respiratory arrest.
A low respiratory rate (\<12 breaths/minute) is an adverse sign and requires immediate medical attention.
Circulation
Patients typically present with bradycardia. Opioids, especially in IV form, cause vasodilation and hypotension.
Disability
opioid overdose.
Miosis, more commonly referred to as ‘pinpoint pupils’ and a decreased Glasgow Coma Scale (GCS) are clinical features of
Figure 1.An example of miosis.
9
"Below 8, intubate"
\: patients with a GCS score less than 8, of any cause, are unable to protect their own airway, therefore,
are at risk of obstructing it. They may require emergency intubation if the problem cannot be corrected quickly.
Exposure
Look for evidence of recreational drug use, for example, track marks on the arms. If the patient is in chronic pain or an end
of life patient, they may have a syringe driver or a fentanyl patch which may easily be missed.
Look for evidence that would support other causes of reduced consciousness/respiratory depression, for example,
intracranial pathology.
Take extra care in examining these patients. There may be drug paraphernalia around them/in pockets/hidden in clothing
such as dirty needles.

Di

Reduced level of consciousness is a broad and challenging presentation with multiple di
Important di
Hypoglycaemia\: should be actively excluded in any patient presenting with reduced consciousness. Hypoglycaemia
can be quickly diagnosed with a blood glucose reading and easily treated. The patient may have adrenergic (sweating,
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clamminess) and neuroglycopenic symptoms (confusion, drowsiness, aggression).
Post-ictal status\: a temporary state of confusion and depressed consciousness occurring after an epileptic seizure,
typically lasting up to an hour, or longer in severe seizures.
Overdose with other depressants\: most commonly alcohol. Others include hypnotic drugs such as zopiclone, or
benzodiazepines such as diazepam.
Head injury or other intracranial pathology\: often obvious from the collateral history or paramedics’ handover. Look for
evidence of head injury for example lacerations and bruising, or from the history, for example, sudden onset occipital
headache then loss of consciousness (typical of subarachnoid haemorrhage).
Carbon dioxide narcosis\: a state of reduced consciousness caused by carbon dioxide poisoning, typically occurs in
those with chronic type 2 respiratory failure, for example, patients with chronic obstructive pulmonary disease. The
patient will often feel warm and vasodilated with a bounding peripheral pulse.

Investigations

Bedside investigations

Relevant bedside investigations include\:
Observations (vital signs)\: to see if this patient needs urgent intervention and physiological support, for example,
supplemental oxygen for low saturations.
Arterial blood gas\: to assess for evidence of type 2 respiratory failure and acidosis which may occur in opioid overdose
secondary to respiratory depression.
Capillary blood glucose\: to rule out hypoglycaemia.

Bloods

Relevant blood tests include\:
FBC\: important to obtain a baseline.
U&E\: to check if this patient is unknowingly accumulating opioids in their system due to renal impairment.
LFTs\: to assess if the patient can metabolise their opioid load e
secondary to overdose (e.g. mixed overdose with paracetamol). Chronically elevated liver enzymes may indicate viral
hepatitis (often associated with intravenous drug use).
Paracetamol levels\: to rule out mixed overdose.
Paracetamol levels
It is considered good practice to take baseline blood tests (FBC, U+E, LFTs) and paracetamol levels from any patient
presenting with overdose, regardless of the ingested substance.
A patient who intends to end their life, has drunk alcohol with their overdose (very common), and/or is drowsy or
confused may not inform you of a potentially fatal paracetamol overdose, which has very few acute clinical features.

Imaging

A CT head should be performed if the patient's level of consciousness does not improve after initial management (e.g. no
response to Naloxone) to rule out intracranial pathology (should be discussed with a senior clinician

Management

Acute management

Removal of source
syringe driver).
If possible, without endangering yourself or others, remove the source of opioid overdose (e.g. transdermal patch or
Monitoring
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Patients who have overdosed on opioids have the potential to deteriorate rapidly (e.g. due to airway obstruction, respiratory
arrest etc) and therefore should be monitored closely in an appropriate setting (e.g. monitoring bay).
Medical
You should assess and manage and life-threatening emergencies as you encounter them as part of an ABCDE approach.
See the Geeky Medics article here for more detailed information.
Many patients require airway management and even ventilation support; this may be temporary until their opioid overdose
is reversed, or for a longer time in a critical care unit if this cannot be achieved in a timely manner.
The mainstay of treatment of opioid overdose involves the use of a competitive opioid receptor antagonist such as
naloxone.
Naloxone can be administered via intravenous, intramuscular, subcutaneous, intranasal, and oral routes. The oral route is
used in the treatment of opioid-induced constipation and not in the acute setting.
Naloxone can be used as a diagnostic tool in the unconscious patient where the cause of loss of consciousness is unclear.
A response to naloxone, represented by an improvement in the GCS score, miosis and respiratory rate, indicates the
presence of opioid overdose. Alternative diagnoses should be considered if there is no response to naloxone.
Opioid reversal with naloxone is almost instant if given in su
life of naloxone is 60-90 minutes whereas the half-life of most opioids is signi
improvement followed by recurrence of opiate overdose features if further doses of naloxone are not administered. 6
As a
result, patients need to be closely monitored for an extended period until the opiates in their system have been cleared.
Naloxone is commonly administered in repeat intravenous (IV) boluses titrated to e
rapid onset of action and the ability to easily titrate doses.
However, there are times when di
Intravenous drug users\: there is a risk that once overdose has been reversed (or partially reversed), these patients will
abscond only to relapse into a coma as the antagonist e
emerge. A simultaneous intramuscular (IM) dose of naloxone may be administered with the IV dose as a means of
reducing the likelihood of this occurring.
Chronic pain or palliative care patients\: it is not desirable to fully reverse the e
patients as you risk causing signi
dose to reverse the toxidrome without reversing all the desirable analgesic e
High opioid load\: sometimes patients have such a high opioid load (e.g. a large overdose, reduced renal excretion) that it
is di
until they have cleared adequate amounts of opiate from their system.
At home/out of hospital use\: In the United Kingdom, Public Health England has updated their regulations, which now
allow any person from a ‘drug treatment service’ to provide naloxone (e.g. recreational drug users at risk, hostel
managers and police o7
Chronic pain and palliative care patients often have home naloxone kits for self or
assisted administration in case of accidental overdose.

Long term management

Patients presenting with an intentional overdose will require mental health assessment and the involvement of psychiatric
services if appropriate. If the patient has children at home, social services may need to be involved.
Patients presenting with unintentional overdose require a thorough review of their current medication regime and
education on the risks of opiate overdose. If the patient was using recreational drugs, they will require referral to local drug
cessation services.

Complications

Opioid overdose

Untreated signi
cause of mortality in opioid overdose.
Acute lung injury following heroin overdose is a well-recognised complication and presents similarly to acute respiratory
distress syndrome (ARDS).
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Naloxone treatment

Naloxone is an uncomplicated drug with a very safe side e
precipitation of acute withdrawal syndrome, and nausea and vomiting although these are usually short-lived.
7

References

O
[LINK].
World Health Organisation. O p i o i d o v e r d o s e . Published in 2020. Available from\: [LINK]
A Rosenblum et al. O p i o i d s a n d t h e t r e a t m e n t o f c h r o n i c p a i n \: C o n t r o v e r s i e s , c u r r e n t s t a t u s , a n d f u t u r e d i r e c t i o n s . Published
in 2008. Available from\: Experimental Clinical Psychopharmacology, 16(5), 405-416.
V Sharma et al. O p i o i d p h a r m a c o l o g y \: a r e v i e w . Published in 2015. Available from\: International journal of scienti
in science and technology, volume 1, issue 5.
J Kirchheiner et al. P h a r m a c o k i n e t i c s o f c o d e i n e a n d i t s m e t a b o l i t e m o r p h i n e i n u l t r a-r a p i d m e t a b o l i z e r s d u e t o C Y P 2 D 6
d u p l i c a t i o n . Published in 2007. Available from\: The Pharmacogenomics Journal, 7, 257-265.
S Clarke et al. N a l o x o n e i n o p i o i d p o i s o n i n g \: w a l k i n g t h e t i g h t r o p e . Published in 2005. Available from\: Emergency Medicine
Journal, 22, 612-616.
Gov.uk. W i d e n i n g t h e a v a i l a b i l i t y o f n a l o x o n e . Published in 2019. Available from\: [LINK].
E Schiller et al. O p i o i d O v e r d o s e . Published in 2020. Available from\: [LINK].
Figure 1. Thomas Bonini. M i o s i s c a u s e d b y o p i o i d c o n s u m p t i o n . License\: [Public Domain]. Available from\: [LINK]

Reviewer

Emergency Medicine Consultant

Related notes

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Test yourself

Contents

Introduction
Aetiology
Risk factors
Clinical features
Di
Investigations
Management
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