Opiates & Opioids

1. Opiates and Opioids,
Intoxication & Treatment
Bhavya Koganti
Sowmiya Lakshmi Rajendiran
Group no. 03a
6th Year 2nd Semester – 2020 October
Tbilisi State Medical University, Georgia

2. ● Since majority of patients overdosed on opiates are lethargic or comatose, the history is usually
obtained from family, friends, bystanders, and emergency medical service providers.
● On many occasions at the scene, one may find pills, empty bottles, needles, syringes and other
drug paraphernalia.
● Other features that one should try and obtain in the history are the amount of drug ingested, any
congestion, and time of ingestion.
● In the pre-hospital setting, sometimes EMS personnel may administer naloxone, which may
help make the diagnosis of opiate overdose.
 Physical Examination
● May be lethargic or have a depressed level of consciousness.
● Opiate overdose will also cause respiratory depression, generalized central nervous system
(CNS) depression, and miosis.
● However, miosis is not universally present in all patients with opiate overdose and there are
many other causes of respiratory depression.
● Other features of opiate overdose include euphoria, drowsiness, change in mental status,
fresh needle marks, seizures and conjunctival injections.
History and Physical

3.  Skin
● Examination of extremities may reveal needle track marks if IV opiates are abused.
● Morphine and heroin are also injected subcutaneously by many addicts.
● In some cases, the opium oil may be inhaled, and the individual may also have patch marks on the
body from the use of fentanyl.
● Most opiates can cause the release of histamine which can result in itching, flushed skin, and urticaria.
 Neurological
● Ability to lower the threshold for seizures, and generalized seizures can occur, especially in young
children. This is primarily due to paradoxical excitation of the brain.
● In adults with seizures, the 2 opiates most likely involved are propoxyphene or meperidine.
● In rare cases, hearing loss may be noted especially in individuals who have consumed alcohol with
heroin. However, this auditory deficit is reversible.
 Cardiovascular
● Peripheral vasodilatation, which can result in moderate to severe hypotension.
● However, this hypotension is easily reversed with changes in body position or fluid administration.
● If the hypotension is severe and is unresponsive to fluids, then one must consider other co-ingestants.
Continued;

4.  Pulmonary
● In some cases of morphine toxicity, the respiratory distress and hypoxia may, in fact, present with
pupillary dilatation.
● In addition, drugs like meperidine, morphine, propoxyphene and diphenoxylate/atropine are known to
cause midpoint pupils or frank mydriasis.
● The breathing is usually impaired in patients with a morphine overdose. One may observe shallow
breathing, hypopnea, and bradypnea.
● The respiration rate may be 4 to 6 breaths per minute and shallow.
● Since opiates can also cause bronchoconstriction, some individuals may present with dyspnea,
wheezing and frothy sputum.
 Gastrointestinal
● Both nausea and vomiting are also seen in patients with opiate toxicity;. The reason is that opiates
can cause gastric aperistalsis and slow down the intestine motility.
 Psychiatric Features
● Even though opiates are generalized CNS depressants, they can cause the following neuropsychiatric
symptoms: Anxiety, Agitation, Depression, Dysphoria, Hallucinations, Nightmares, Paranoia
Continued;

5. ● It is important to always consider opiate overdose or toxicity in a lethargic patient
with no other identifiable cause.
● Many of the individuals who abuse opiates also tend to use other illicit agents like
cocaine and prescription drugs like the antidepressants and benzodiazepines at the
same time.
● Suspicion of co-ingestants should be raised when the usual clinical signs and
symptoms of opiate toxicity differ, and the patient fails to respond to the opiate
antagonist, naloxone.
 Imaging Studies
● If any lung injury is suspected, a chest x-ray should be obtained.
● If the patient is suspected of being a body packer, then an abdominal x-ray
should be obtained.
Evaluation

6.  Electrocardiography
● An ECG is recommended in all patients with suspected opioid overdose.
Coingestants like the tricyclics have the potential to cause arrhythmias.
 Laboratory Studies
● Drug screens are readily available but often do not change initial management of
straightforward cases.
● Drug screens when performed on urine and are quite sensitive.
● In most cases, a positive opiate result will show up even 48 hours post exposure.
● In patients with opiate toxicity or overdose the following blood work is usually
performed:
• Complete blood cell count
• Comprehensive metabolic panel
• Creatine kinase level
• Arterial blood gas determinations
Continued;

7.  Management at the Scene
● The care of the patient at the scene depends on the vital signs.
● If the patient is comatosed and in respiratory distress, airway control must be obtained
before doing anything else.
● Endotracheal intubation is highly recommended for all patients who unable to protect their
airways.
● If there is suspicion of opiate overdose, then naloxone should be administered to reverse the
respiratory depression.
● Naloxone can also cause agitation and aggression when it reverses the opiate. If the individual
is a drug abuser, the lowest dose of naloxone to reverse respiratory apnea should be
administered.
● In the ambulance, the patient may become combative or violent, and use of restraints may be an
option.
● If the individual has no intravenous access, one may administer the naloxone intramuscularly,
intranasally, intraosseous or via the endotracheal tube.
● Data show that intranasal route is as effective as intramuscular route in the pre-hospital setting.
Treatment / Management

8.  Emergency Department Care
● The ABCDE protocol has to be followed.
● If there is any sign of respiratory distress or failure to protect the airways in an un-intubated
patient with a morphine overdose, one should not hesitate to intubate.
● If any suspicion of occult trauma to the cervical spine, immobilization should be a priority.
● Patients who present with an unknown cause of lethargy or loss of consciousness have their
blood glucose levels drawn.
● Initial treatment of overdose begins with supportive care. This includes assistance in
respiration, CPR if no spontaneous circulation is occurring, and removal of the opioid
agent if a patch or infusion are delivering it.
● If the physician suspects that the individual has overdosed on an opiate and has signs of
respiratory and CNS depression, no time should be wasted on laboratory studies; instead,
naloxone should be administered as soon as possible.
● Naloxone is a competitive antagonist of the opiate receptor. It can be administered by
intravenous, intramuscular, subcutaneous, or intranasal routes.
● Additionally, it can be used in an off-label manner by administering it via endotracheal tube or
in a nebulized form, though research on the efficacy of tracheal absorption has only been
Continued;

9.  Role of Activated Charcoal
● If the patient is alert at the time of admission, activated charcoal can be used to
decontaminate the gastrointestinal tract in patients with opiate overdose.
● While normally activated charcoal usually has to be administered within 1 hour of ingestion
of a drug to be effective, with opiates, there is slowing of gastric motility, and hence,
activated charcoal can be given as late as 2 to 3 hours after ingestion.
● As long as there are no contraindications, activated charcoal should be administered to all
symptomatic patients with opiate overdose.
● If the patient is not alert, then airway protection is necessary; some patients will require
endotracheal intubation prior to the administration of activated charcoal to prevent
aspiration.
● If activated charcoal enters the airways, the result can be catastrophic.
● In some patients, orogastric lavage may help.
Continued;

10.  Bowel Irrigation
● The role of whole bowel irrigation may be considered in people who have ingested drug
packets containing opiates, but there are no controlled studies to determine if this treatment has
any benefit or improves outcomes.
● However, whole body irrigation is not recommended in patients who show signs of ileus,
bowel obstruction, have obvious signs of peritonitis, hemodynamic instability or an
unprotected airway.
 Use of Buprenorphine/Naloxone
● Buprenorphine in combination with naloxone is widely available and is used to treat opiate
use disorder.
● This formula has also been used to used narcotic overdose. The big advantage of using this
combination is that it reduces the withdrawal symptoms for 24 to 36 hours. Anecdotal data
indicate that the risk of overdose is small with buprenorphine/naloxone compared to
methadone. Unfortunately, the sublingual preparation of buprenorphine and naloxone can
also be easily abused sublingually
Continued;

11. ● Clonidine toxicity
● Cyanide toxicity
● Diabetic ketoacidosis
● Ethylene glycol toxicity
● Gamma-hydroxybutyrate toxicity
● Hypercalcemia
● Hypernatremia
● Hypothermia
● Meningitis
● Neuroleptic agent toxicity
Differential Diagnosis

12.  Mortality/Morbidity
● Major cause of morbidity and mortality is due to respiratory depression.
● Rarely the individual may develop seizures, acute lung injury and adverse cardiac events.
● In individuals with prior lung pathology who overdose on opiates, the risk of respiratory
distress and death is much higher than in the normal population.
● The other reason for the opiate toxicity may be due to co-ingestants, and the eventual
toxicity depends on the type of co-ingestant.
● In one Canadian study, the risk of fatal opiate toxicity was doubled when the opiate was
ingested with gabapentin; the latter is also known to depress respiration.
● Finally, the morbidity and mortality also depend on the reason why the opiate was
ingested; some people are intent on committing suicide, and these individuals often take
several other drugs at the same time, thus, greatly increasing the risk of death.
 Prognosis
● If the patient does arrest in the setting of a pure opiate overdose, the cause in most cases is
severe hypotension, hypoxia and poor perfusion of the brain.
● The outcome for these patients is poor.
Prognosis

13. ● Narcotic Bowel Syndrome
- Characterized by frequent episodes of moderate to the severe abdominal pain that
worsens with escalating or continued doses of opiates.
- Occur in people with no prior bowel pathology and is a maladaptive response.
- The syndrome can also be associated with intermittent vomiting, abdominal
distension, and constipation.
- Eating always aggravates the symptoms, and the condition can last for days or weeks.
- Anorexia can lead to body weight loss. There is delayed gastric emptying and
intestinal transit.
- The syndrome is often confused with bowel obstruction. The key to the diagnosis is
the recognition of continued and escalating doses of opiates that worsen the abdominal
pain, instead of providing relief.
- The treatment is some psychotherapy combined with tapering or discontinuing the
opioid.
- The key to successful treatment is to develop a strong patient-physician relationship
and trust with the patient; the narcotic should be gradually withdrawn, and other non-
pharmacological treatments used to manage pain.
Complications

14. ● Withdrawal Reaction
- Withdrawal symptoms following cessation of opiates are common, but the symptoms
are often vague and not as severe as those observed with alcohol or benzodiazepines
discontinuation.
- The onset of symptoms depends on the drug ingested and usually occur within 2 to 4
days with methadone and 8 to 10 hours after meperidine.
- The autonomic symptoms may include excessive lacrimation, sweating, piloerection,
rhinorrhea, repeated yawning, myalgia, nasal congestion, diarrhea and abdominal cramps.
- The symptoms usually peak between 36 to 48 hours and gradually subside in 72 hours.
- In chronic drug addicts, the symptoms may last for 7 to 14 days.
- The treatment of withdrawal symptoms is supportive.
- The use of additional opiates to counter the symptoms of withdrawal is not
recommended.
- For severe withdrawal cases, one may use clonidine, especially when methadone may
be inappropriate or unavailable.
- After the acute treatment, the patient should be recommended to join a long-term drug
rehabilitation program to prevent relapse.
Continued;

15. ● Acute Lung Injury
- Well known to occur after a heroin overdose.
- However, acute lung injury can also occur following methadone and propoxyphene
overdose and is universally present in patients who expire from a high dose of opiate.
- As to how these opiates cause lung injury is not fully understood, but the eventual
result is hypoventilation and hypoxia.
- Clinically, heroin-induced lung injury will present with sudden onset of dyspnea,
frothy sputum, cyanosis, tachypnea, and rales- features consistent with pulmonary
edema.
- Also in children who have ingested high doses of opiates.
- Acute lung injury is very similar to ARDS in presentation, and most cases clear up
with aggressive airway management and oxygen.
- The usual drugs used to manage pulmonary edema are not used, and in fact, the use
of diuretics may exacerbate the hypotension.
Continued;

16. ● Infection
- In individuals who use intravenous opioids, complications include abscess, cellulitis,
and endocarditis.
- The most common organisms involved are the gram-positive bacteria
like Staphylococcus and Streptococci.
- If the bacteria enter the systemic circulation, the risk of epidural abscess and
vertebral osteomyelitis are other potential complications.
- These patients may present with fever and continuous back pain.
- Some IV drug abusers are known to inject the opiates directly into the neck, and this
can lead to jugular vein thrombophlebitis, Horner syndrome and even pseudoaneurysms
of the carotid artery.
- Both peripheral and pulmonary emboli have been reported in IV drug users.
- Accidental injection into the nerves has also been reported to cause permanent
neuropathy.
-
Continued;

17. - Infectious Endocarditis is a serious complication of intravenous drug abuse.
- Often these individuals use a mixture of illicit drugs and dirty needles.
- The Diagnosis is often difficult as the symptoms are vague initially.
- Although in most cases, the right-sided heart valves are affected, sometimes the
left-sided valves may also be involved.
- The most common valves involved in intravenous drug users is the tricuspid
valve.
- It often presents with fever, malaise and a new murmur.
- In some patients, recurrent septic pulmonary embolism may be the only
presenting feature.
- The most common organism involved in right-sided endocarditis is
Staphylococcus aureus,
- but left-sided endocarditis may be polymicrobial and include Streptococcus, E.
coli, Pseudomonas or Klebsiella.
- In most patients, when the left-sided valves are involved, the symptoms and signs are
usually more obvious compared to right-sided involvement.
Continued;

18. - Other manifestations of opioid abuse may be recurrent pneumonia,
- and aspiration pneumonia may also occur with the individual is unconscious.
- Rhabdomyolysis is not an uncommon complication of opiate overdose.
- It may occur even in the absence of a compartment syndrome.
- Another life-threatening complication is necrotizing fasciitis that often presents
with severe pain, fever, dark, dusky skin with crepitus.
- The individual will show signs of septic shock.
- Aggressive resuscitation and immediate surgical debridement can be life-saving.
- Seizures: Opiates are known to increase the risk of seizures, especially drugs like
propoxyphene, meperidine, pentazocine, intravenous fentanyl, and heroin.
- The individual may present with a prolonged seizure which may result as a result
of CNS hypoperfusion and hypoxia or a result intracranial injury due to a fall.
Continued;

19. References
 https://www.ncbi.nlm.nih.gov/books/NBK470415/
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851054/
 https://www.ncbi.nlm.nih.gov/books/NBK431077/
 https://www.ncbi.nlm.nih.gov/books/NBK459161/
 https://www.ncbi.nlm.nih.gov/books/NBK526012/
 Wang S. Historical Review: Opiate Addiction and Opioid Receptors. Cell Transplant. 2019
Mar;28(3):233-238. [PMC free article] [PubMed]
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Misuse and Addiction: A Review. JAMA Psychiatry. 2019 Feb 01;76(2):208-
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