Opiate Poisoning

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:

• Codeine
• Dextromoramide (withdrawn)
• Dextropropoxyphene (withdrawn)
• Diamorphine
• Dihydrocodeine
• Fentanyl
• Heroin
• Loperamide
• Meptazinol
• Methadone
• Morphine
• Opium
• Oxycodone
• Pentazocine
• Tramadol

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

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 7072 deaths involving heroin/morphine (86% males) and 3298 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.

Methadone deaths per 1000 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 females.³

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.⁴
• A significant incidence in recently-released prisoners has been identified.⁵
• 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
• Dextropropoxyphene, in co-proxamol (now withdrawn), is very rapid in onset and can kill swiftly from respiratory depression.⁶

The following groups are at risk of morphine toxicity and usually require a lower dose:⁷

• Hepatic impairment may produce coma but many such patients tolerate morphine well
• Reduce dose or avoid in renal impairment, elderly and debilitated
• Hypotension
• Hypothyroidism
• Asthma (avoid during attack) and decreased respiratory reserve
• Prostatic hypertrophy

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 to 50% at a time.⁸

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 or other sedatives involved. There may be nausea or vomiting.

Signs

• Respiratory depression may be apparent. Hypotension and tachycardia are possible. There is usually pin-point pupils but this may be absent if other drugs are involved.
• The 'post mortem 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.¹⁰

There may be no clear indication of what the patient has taken. He may be a known drug abuser or there may be needle track marks on the limbs. Beware of multiple drug ingestion, eg 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:

• Diabetic ketoacidosis
• Hypercalcaemia
• Hypernatraemia
• Hyperosmolar hyperglycaemic nonketotic coma
• Hypoglycaemia
• Hyponatraemia
• Hypothermia
• Meningitis
• Stroke
• Subdural haematoma
• Syncope

• 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 ll 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 FBC, metabolic screen, creatine kinase level and arterial blood gases.
• A chest Xray may be indicated if pulmonary oedema is suspected.
• Abdominal Xray should be performed if ingestion of packages is suspected in patients who are suspected of being drug carriers, although a negative Xray does not rule out the condition.
• ECG should as a general rule be considered in all patients.

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

Non-Drug

• Do not delay establishing a clear airway, adequate ventilation and oxygenation if consciousness is impaired.
• Give oral activated charcoal, provided the airway can be protected, if a substantial amount has been ingested within 2 hours.

Drugs

• Give naloxone intravenously (0.4 to 2 mg for an adult and 0.01 mg/kg body weight for children) if coma or respiratory depression is present. Give 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. Intramuscular naloxone 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 intravenous 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.^14,15 They are often reluctant to call for help.
• Intravenous 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.
• Naltrexone is recommended by 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.¹⁶ 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.

The development of non-cardiogenic pulmonary oedema carries a poor prognosis (it is not naloxone reversible). Multiple drug ingestion and co-morbidity (e.g. cardiac or renal conditions) also increases the risk of death.¹⁷

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.³