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Opiate Poisoning

This PatientPlus article is written for healthcare professionals so the language may be more technical than the condition leaflets. You may find the abbreviations list helpful.

Opiate poisoning can occur at any time from birth (when pethidine given to the mother in labour may suppress ventilation) to terminal care. The outcome can range from discomfort like constipation to death from respiratory depression.
The following drugs may be involved:

They may come alone or in combination when the situation becomes more complex.

Epidemiology

It is difficult to get reliable incidence figures. The elderly are more liable to poisoning from opiates and more likely to be taking them, especially drugs like co-codamol for arthritis.

Drug-related deaths from heroin usually involve other drugs too. Death from heroin overdose alone is uncommon.1,2 The Office of National Statistics (ONS) published figures for the period 1993-2004. During this period here were 7,072 deaths involving heroin/morphine (86% males) and 3,298 deaths involving methadone (83% male).

Mortality rates for methadone decreased between 1997 and 2004 to just above 1993 levels. Among females the mortality rate for both drugs was lower than for males throughout the study period, remaining relatively stable.

A rise in drug-related deaths in Scotland was seen in 2006; this was thought to be a late effect of the increase in the use of injectable drugs in the 1980s.3

Methadone deaths per 1,000 patient years remained similar between 1993 and 1997, after which they fell by three-quarters. The authors of the ONS study believe this to be a vindication of the use of methadone to treat heroine addicts (the 'British method'). Deaths usually occurred in the age range 30-32 and were 3 to 4 times as common in males as in females.4

A more recent Australian study of fatal methadone and heroin toxicity cases, however, found that methadone users were significantly more likely than heroin users to have cardiac, pulmonary, hepatic and renal disease.5

Risk factors

  • Studies of the psychosocial background of drug abusers who died from opiate poisoning show a strong correlation between mental health conditions, financial problems and crime. Being in a relationship tends to have a protective effect.6
  • A significant incidence in recently released prisoners has been identified.7
  • One study at the Edinburgh Royal Infirmary found that a high proportion of drug-related deaths occurred in people who had used the hospital in the last five years.8
  • Opiates produce tachyphylaxis. This means that with time larger and larger doses are needed to obtain the same effect and tolerance develops to the adverse effects. It is not uncommon to find a drug abuser or a patient in terminal care who is taking a daily dose that would be fatal to a normal person. If dosage is reduced or stopped this tolerance quickly fades. If they take what was formerly 'a good hit' it has become a fatal overdose.1
  • Alcohol and other sedatives enhance the effect of opiates, especially respiratory depression. Drug abusers often like to enhance the effect of heroin with benzodiazepines. This is very dangerous.1

The following groups are at risk of morphine toxicity and usually require a lower dose:9

Opiates should still be used in terminal care, even in these groups. Since the Harold Shipman case some doctors are wary about the dose they give, even in terminal care. If this means that dying patients are denied adequate analgesia, it is to be regretted. Morphine or diamorphine can safely be titrated upwards by 30-50% at a time.10

Presentation9,11

Symptoms

  • Opiate poisoning may be a chronic problem, in which case the main complaint will be of constipation. There may be nausea, vomiting or just loss of appetite. There may be sedation and craving for the next dose.
  • Acute toxicity presents with drowsiness that will be more severe if there is also alcohol involved, or involvement of other sedatives. There may be nausea or vomiting.

Signs

  • Respiratory depression may be apparent. Hypotension and tachycardia are possible. There are usually pinpoint pupils but this sign may be absent if other drugs are involved.
  • The 'postmortem sole incision' sign has recently been identified. This is an incision made in the sole by an acquaintance in the belief that this subsequent blood loss will reduce the likelihood of death in an individual who has taken an accidental overdose of an opiate.12

Differential diagnosis13

There may be no clear indication of what the patient has taken. He or she may be a known drug abuser or there may be needle track marks on the limbs. Beware of multiple drug ingestion, e.g. paracetamol with co-codamol or alcohol or benzodiazepines especially in drug abusers or with suicidal intent.

Other conditions which may need to be considered include:

Investigations13

  • It is possible to get a urine screen for drugs of abuse and there are even some sticks available that will give a quick result. However, they merely detect the presence of opiates or methadone and give no indication of quantity.
  • A paracetamol blood level should be considered for all patients who have overdosed or self-poisoned.
  • If in doubt give a test dose of naloxone, repeated in 2 minutes if there is no result. If the patient is opiate-dependent this will produce a very severe, acute and unpleasant withdrawal syndrome.
  • Baseline pathology investigations should be performed in patients with moderate-to-severe toxicity, including full blood count, metabolic screen, creatine kinase level and arterial blood gases.
  • A chest X-ray may be indicated if pulmonary oedema is suspected.
  • Abdominal X-ray should be performed if ingestion of packages is suspected in patients who are suspected of being drug carriers, although a negative X-ray does not rule out the condition.
  • ECG should, as a general rule, be considered in all patients.

Associated diseases14,15

Drug abusers may possibly carry hepatitis B. Intravenous abusers have a 70-90% chance of carrying hepatitis C. There may possibly be HIV infection. Nutrition and self-care are usually poor.

Management13

  • Do not delay establishing a clear airway, adequate ventilation and oxygenation if consciousness is impaired.
  • Give naloxone intravenously (IV) (0.4-2 mg for an adult and 0.01 mg/kg body weight for children) if coma or respiratory depression is present.
    • Give intramuscularly (IM) if no vein is available. Repeat the dose if there is no response within two minutes. Naloxone is a competitive antagonist and large doses (4 mg) may be required in a severely poisoned patient.
    • Failure of a definite opiate overdose to respond to large doses of naloxone suggests that another central nervous system (CNS) depressant, or brain damage, is present.
    • Observe the patient carefully for recurrence of CNS and respiratory depression. The plasma half-life of naloxone is shorter than that of all opioid analgesics. Repeated doses may be required. Naloxone IM should be considered if the patient is threatening to self-discharge as it may help reduce the risk of respiratory arrest when the IV naloxone wears off.
    • If someone takes an overdose of IV heroin it is important to administer naloxone as soon as possible. Often this is done by paramedics but some people have advocated that users should have a supply in case one of their number overdoses and treatment can be started without delay.16 They are often reluctant to call for help.
    • IV infusions of naloxone may be useful where repeated doses are required. An infusion of 60% of the initial dose per hour is a useful starting point. A solution containing 10 mg (25 vials) made up in 50 mL dextrose will produce a 200 micrograms/mL solution for infusion using an IV pump (dose adjusted to clinical response). Infusions are not a substitute for frequent review of the patient's clinical state.
  • Give oral activated charcoal, provided the airway can be protected, if a substantial amount has been ingested within 2 hours.
  • Naltrexone is recommended by the National Institute for Health and Clinical Excellence (NICE) as a treatment option for people who have been opioid dependent but who have stopped using opioids and who are highly motivated to stay free from the drugs in an abstinence programme.17 It is a competitive opiate antagonist that will block the effect of heroin. It should only be given to people who have been told about the problems associated with treatment and with proper supervision. Treatment with naltrexone should be given as part of a support programme to help the person manage their opioid dependence.
  • If body packing of opioids is suspected or confirmed, whole-bowel irrigation should be administered.

Prognosis

The development of noncardiogenic pulmonary oedema (also known as acute lung injury) carries a poor prognosis (it is not naloxone reversible). Multiple drug ingestion and comorbidity (e.g. cardiac or renal conditions) also increase the risk of death.18

Prevention1

Drug abusers must be educated about the risks they face. They must understand loss of tolerance after reduction therapy or enforced abstinence as in prison. They must understand the enhanced risk with benzodiazepine use too. They are much less likely to get a serious overdose if they inhale rather than inject.

Daily dispensing of methadone with supervised consumption has greatly reduced the risks.4


Document references

  1. Oliver P, Keen J; Concomitant drugs of misuse and drug using behaviours associated with fatal opiate-related poisonings in Sheffield, UK, 1997-2000. Addiction. 2003 Feb;98(2):191-7. [abstract]
  2. Hickman M, Carrivick S, Paterson S, et al; London audit of drug-related overdose deaths: characteristics and typology, and implications for prevention and monitoring. Addiction. 2007 Feb;102(2):317-23. [abstract]
  3. Bird SM, Hutchinson SJ, Hay G, et al; Missing targets on drugs-related deaths, and a Scottish paradox. Int J Drug Policy. 2010 May;21(3):155-9. Epub 2009 Nov 7. [abstract]
  4. Morgan O, Griffiths C, Hickman M; Association between availability of heroin and methadone and fatal poisoning in England and Wales 1993-2004. Int J Epidemiol. 2006 Dec;35(6):1579-85. Epub 2006 Oct 30. [abstract]
  5. Darke S, Duflou J, Torok M; The comparative toxicology and major organ pathology of fatal methadone and Drug Alcohol Depend. 2010 Jan 1;106(1):1-6. Epub 2009 Aug 31. [abstract]
  6. Oliver P, Horspool M, Rowse G; A psychological autopsy study of non-deliberate fatal opiate-related overdose 2008 National Treatment Agency for Substance Misuse
  7. Farrell M, Marsden J; Acute risk of drug-related death among newly released prisoners in England and Wales. Addiction. 2008 Feb;103(2):251-5. [abstract]
  8. Thanacoody RH, Jay J, Sherval J; The association between drug related deaths and prior contact with hospital-based Scott Med J. 2009 Nov;54(4):7-10. [abstract]
  9. Summary of Product Characteristics, Oramorph Oral Solution®; Summary of Product Characteristics - Oramorph Oral Solution®, Boehringer Ingelheim Limited, electronic Medicines Compendium. Dated September 2010.
  10. Palliative care - pain; Palliative cancer care - pain, Clinical Knowledge Summaries (March 2009)
  11. Opioids; International Program on Chemical Safety (INCHEM) 2008
  12. Benomran F; Postmortem sole incisions - A new sign of heroin overdose? J Forensic Leg Med. 2008 Jan;15(1):59-63. Epub 2006 Nov 16. [abstract]
  13. Stephens E; Toxicity, Narcotics, eMedicine, Apr 2010
  14. Cooper CL, Mills EJ; Therapeutic challenges in hepatitis C-infected injection drug using patients. Harm Reduct J. 2006 Nov 10;3:31. [abstract]
  15. Des Jarlais DC, Fisher DG, Newman JC, et al; Providing hepatitis B vaccination to injection drug users: referral to health clinics vs on-site vaccination at a syringe exchange program. Am J Public Health. 2001 Nov;91(11):1791-2.
  16. Seal KH, Downing M, Kral AH, et al; Attitudes about prescribing take-home naloxone to injection drug users for the management of heroin overdose: a survey of street-recruited injectors in the San Francisco Bay Area. J Urban Health. 2003 Jun;80(2):291-301. [abstract]
  17. Drug misuse - naltrexone, NICE Technology Appraisal Guidance (2007); Naltrexone for the management of opioid dependence
  18. Opiates; General Management of Acute Poisoning, University of Cambridge, 2003

Internet and further reading

Acknowledgements

EMIS is grateful to Dr Laurence Knott for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2011.
Document ID: 2542
Document Version: 24
Document Reference: bgp1386
Last Updated: 27 Aug 2010
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