Pain & Sedation
A 45 year old man presents to the Emergency Department with severe abdominal pain. He scores his pain 10/10 despite taking paracetamol and ibuprofen at home. You plan to give intravenous morphine. Which of the following is a contraindication to the use of opioid analgesia?
Answer:
Do not prescribe opioids to people who have:- A risk of paralytic ileus (opioids reduce gastric motility)
- Acute respiratory depression (risk of further respiratory depression)
- An acute exacerbation of asthma (opioids can aggravate bronchoconstriction as a result of histamine release)
- Head injury or raised intracranial pressure (opioids interfere with pupillary responses vital for neurological assessment and may cause retention of carbon dioxide)
Opioid Pharmacology
Pain & Sedation
Last Updated: 13th February 2024
Opioid analgesics are usually used to relieve moderate to severe pain particularly of visceral origin. Repeated use of opioid analgesics can result in tolerance and dependence, although this is less relevant in the acute clinical context. Opioid dependant patients may require much higher doses of opioids to control their pain.
Mechanism of action
Opioid analgesics mimic endogenous opioid peptides by causing prolonged activation of opioid receptors that are widely distributed throughout the central nervous system, primarily the mu(μ)-receptors which are the most highly concentrated in brain areas involved in nociception.
Activation of these opioid receptors produces a range of central effects including analgesia, respiratory depression (direct inhibition of respiratory centre in brainstem), euphoria, sedation, postural hypotension (depression of the vasomotor centre), miosis (IIIrd nerve nucleus stimulation), nausea/vomiting (stimulation of chemoreceptor trigger zone) and constipation (decreased GI motility).
Choice of opioid
- Codeine
- Codeine phosphate is a weak opioid and can be used for the relief of mild to moderate pain where other painkillers such as paracetamol or ibuprofen have proved ineffective.
- Codeine is metabolised to morphine which is responsible for its therapeutic effects. Codeine 240 mg is approximately equivalent to 30 mg of morphine.
- The capacity to metabolise codeine can vary considerably between individuals; there is a marked increase in morphine toxicity in people who are ultra rapid metabolisers, and reduced therapeutic effect in poor codeine metabolisers. Codeine is contraindicated in patients of any age who are known to be CYP2D6 ultra-rapid metabolisers.
- Codeine is also contraindicated in children under 12, and in children of any age who undergo the removal of tonsils or adenoids for the treatment of obstructive sleep apnoea.
- Tramadol
- Tramadol may be prescribed for the treatment of moderate to severe pain, and may have special use for neuropathic pain.
- Tramadol produces analgesia by two mechanisms: an opioid effect and an enhancement of serotonergic and adrenergic pathways. It has fewer of the typical opioid side-effects (notably, less respiratory depression, less constipation and less addiction potential); but psychiatric reactions have been reported.
- Morphine
- Morphine is the standard against which other opioid analgesics are compared.
- Morphine is the most valuable opioid analgesic for severe pain although it frequently causes nausea and vomiting.
- Morphine reaches peak effect within a few minutes when given intravenously and in general provides clinical effect for three to four hours.
- In addition to relief of pain, morphine also confers a state of euphoria and mental detachment.
- Diamorphine
- Whilst there are no differences between parenteral diamorphine and morphine in terms of analgesia and side-effects, diamorphine can be absorbed (rapidly) by the transmucosal route. This has given it a proven role intranasally in children and is an option in adults with difficult venous access.
- Fentanyl
- The key advantage of fentanyl over morphine is its brief action, providing analgesia for 30-45 minutes, thereby giving it a role in procedural sedation.
Contraindications
Do not prescribe opioids to people who have:
- A risk of paralytic ileus (opioids reduce gastric motility)
- Acute respiratory depression (risk of further respiratory depression)
- An acute exacerbation of asthma (opioids can aggravate bronchoconstriction as a result of histamine release)
- Head injury or raised intracranial pressure (opioids interfere with pupillary responses vital for neurological assessment and may cause retention of carbon dioxide)
Cautions
Prescribe opioids with caution in people with:
- Impaired respiratory function or asthma
- Renal impairment (the effects are increased and prolonged)
- Hepatic impairment (adverse effects, such as sedation and constipation, can precipitate hepatic encephalopathy, particularly in people who may decompensate)
- Prostatic hyperplasia (urinary retention has been reported)
- Obstructive or inflammatory bowel disorders (opioids reduce gastric motility)
- Diseases of the biliary tract (ureteric or biliary spasm has been reported)
- Convulsive disorders (tramadol should not be given to people with uncontrolled epilepsy)
- Adrenocortical insufficiency (reduced dose is recommended)
- Hypothyroidism (reduced dose is recommended)
- Elderly or debilitated patients (reduced dose is recommended)
Side effects
All opioids have the potential to cause:
- Gastrointestinal adverse effects
- Nausea, vomiting, constipation, urinary retention
- Central nervous system depression
- Sedation, respiratory depression, confusion
- Cardiovascular effects
- Peripheral vasodilation, hypotension, arrhythmias
- Dependence and tolerance
Additionally, tramadol can cause:
- Convulsions (rarely) — they occur mainly after taking high doses, or during concomitant treatment with drugs which can reduce the seizure threshold or induce convulsions (for example antidepressants or antipsychotics)
- Psychiatric reactions (rarely), for example, hallucinations and confusion
- Hypoglycaemia
- Hyponatraemia
Interactions
All opioids interact with central nervous system depressants such as sedatives or hypnotics, phenothiazines or alcohol. Concomitant use may potentiate the effects of CNS depressants and cause respiratory depression or sedation. Opioids should also be avoided in patients taking monoamine oxidase inhibitors (MAOIs).
Additionally, tramadol interacts with:
- Selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) — increased risk of seizures and serotonin syndrome with concomitant use
- Tricyclic antidepressants (TCAs) — increase risk of seizures with concomitant use
- Carbamazepine — reduces serum tramadol levels
- Warfarin — tramadol has been reported to increase the anticoagulant effects of warfarin
Overdose
In overdose opioids cause coma, respiratory depression, and pinpoint pupils (miosis). Naloxone is a specific antagonist at opioid receptors and reverses respiratory depression caused by opioid drugs.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
