- Physiology of N&V
- Causes of N&V
- Antiemetic Therapy
Nausea is a common symptom that you will be expected to manage appropriately, in much the same way as effectively managing pain. This article runs through a step wise approach to understanding why nausea happens, and thus the best way to manage it effectively.
Physiology of N&V
- Control of vomiting is orchestrated by the Vomiting Centre (VC), a collection of nuclei in the medulla.
- Many inputs from a range of sources which act as triggers (See below)
- Efferent nervous stimulation to trigger vomiting is conducted by cranial nerves 5, 7, 9, 10 and 12, when a specific threshold is reached.
The Vomiting Act
- Deep breath
- Upper oesophageal sphincter relaxation
- Closure of the glottis (protects airway)Soft palate elevation (protects nasal passage)
- Diapragmatic contraction
- Abdominal wall contaction
- Lower oesophageal sphincter relaxation
- Visceral Stimulation
- Chemoreceptor Trigger Zone (CTZ)
- Higher cortical inputs (including vestibular system)
- Afferent fibres mainly from GI tract (but also cardiac)
- Mechanical or chemosensory receptors
- Conducted by both sympathetic and parasympathetic fibres (primarily the Vagus Nerve)
- Triggers: Direct visceral irritation and/or distension
- Neurotransmitters: Seretonin (5HT), Dopamine (DA)
- E.g. Gastroenteritis
- Located on the floor of the 4th ventricle
- Outside the blood brain barrier so exposed to systemic toxins, drugs etc.
- The prime site of ‘systemic’ triggers of vomiting.
- Triggers: Drugs, hormones, toxins, metabolic abnormalities
- Neurotransmitters: 5HT, DA
- E.g. Action of opioids at CTZ, causing nausea.
Higher Neurological Inputs
- Nervous inputs from higher neurological centres, including other cranial nerves.
- CN VIII (vestibular component) in particular can be linked to nausea
- The Gag reflex(CN IX afferent fibres) provides a strong trigger
- As with pain, there is a psychological component of nausea.
- Triggers: Emotions, smells, anticipatory nausea, motion sickness, vertigo, taste, gag reflex
- Neurotransmitters: Acetylcholine (ACh), Histamine (H), 5HT
- E.g. watch, listen and smell someone else being sick. Feeling nauseous?
Causes of N&V
- Obstructions: Small bowel obstruction, pyloric obstruction
- Inflammatory: Pancreatitis, cholecystitis, appendicitis
- Mechanical: gastroperesis,
- Enteric infection: Viral or bacterial
- Cardiac: Don’t forget MI as a cause
- Drugs: Opiates, Antibiotics, cytotoxics, NSAIDs
- Metabolic: High Calcium, Low sodium, Uraemia, DKA, Pregnancy
- Toxins: Alcohol
- Vestibular: Vertigo, Meniere’s disease.
- Intracranial: Raised intracranial pressure, Infection
- Psychological: Fear, anticipatory,
- Sensory: Smell, taste, Pain (can be a trigger in itself)
- Several different classes of antiemetics are available.
- Each have a slightly different efficacy and side effects profile.
- Choice should be guided by your understanding of the process that is causing the nausea.
- Act by blocking H1receptors within the VC
- Also have antimuscarinic properties, leading to some of their side effects profile.
- Good ‘broad spectrum’ of action, though not as potent as other classes in disorders not involving labyrinthine disorders.
- Conversely, the best class for labyrinthine disorders such as vertigo, motion sickness and Meniere’s disease.
- Also first choice in pregnancy associated nausea and vomiting, due to greater experience with them and apparent absence of teratogenic effects.
- Sedation: Particularly with promethazine
- Antimuscarinic properties: dry mouth and blurred vision. Should be used with caution when these actions could be problematic e.g. risk of urinary retention when prostatic hypertrophy, susceptibility to angle closure glaucoma.
- Hypotension: rare but caution demanded in heart failure patients
- Only really used for treatment of motion sickness
- Available in patch form for this indication
- Antimuscarinic properties: as above
Dopamine Receptor Antagonists
- Include the Phenothiazines, Metoclopramide, and Domperidone.
- All act at the CTZ by blocking dopamine receptors.
- Therefore valuable in the sickness caused by drugs, cytotoxics and diffuse malignancy
Phenothiazines and related drugs (the anti-psychotics)
- Have anti-emetic actions at doses lower than for their anti-psychotic indication
- Also has some GI tract effect via its 5HT action.
- This action increases gut motility, and increasing gastro-oesophageal sphincter tone.
- This makes it a particularly effective choice against nausea of a visceral origin e.g. biliary disease.
- It also means it is contraindicated in gastrointestinal obstruction or perforation.
- Unlike the other classes does not cross the blood brain barrier.
- Lower incidence of the central side effects
- Extrapyramidal side effects: Parkinsonian like symptoms, tardive dyskinesias, acute dystonic reactions.
- QT interval prolongation
5HT3 Receptor Antagonists
- Act by blocking the 5HT3 receptors in the CTZ and in the gut.
- Highly effective, particularly against sickness caused by chemotherapy agents and in post operative nausea.
- More expensive so usually a second line agent.
- QT interval prologation: Avoid concomitant use of drugs which do the same
- Weak anti-emetic on own but useful synergist when given with 5HT3 receptor antagonists or some dopamine receptor antagonists.
- Can be given when high likelihood of nausea that may be difficult to control e.g. chemotherapy, previously bad post operative nausea.
- Antiemetics generally avoided where possible unless vomiting is becoming problematic e.g. dehydration.
- Short term use of an antihistamine is first choice, as greater history of use and better evidence of no teratogenic effects.
- Specialist advice should be sought if nausea is problematic for any longer than 48 hours.
- Opioids: cyclizine or dopamine antagonists are usually an effective choice
- Nausea is strongly mediated by 5HT.
- If moderate effects predicted, dexamethasone and metoclopramide are usually sufficient.
- If severe, a 5HT3 receptor antagonist will be employed with dexamethasone, usually to good effect (80% control).
- Risk of N&V can often be identified pre-operatively.
- Risk factors include: female, previous post-op nausea, non-smoker, peri-operative opioid use, general anaesthesia (particularly volatile agents), and type of surgery (particularly abdominal, gynae and ENT procedures).
- Preventative is usually better than reactive treatment, but blanket prophylaxis is not recommended, and should be guided by risk.
- Most classes will be effective, and can be combined as necessary to achieve control.
- Peri-operative antiemetics are frequently used and can be augmented with dexamethasone in higher risk individuals, or when vomiting will be particular problematic e.g. after eye surgery.
- Metoclopramide is one drug which is not as effective for this indication, and so its use is not recommended.
- Hyoscine or an antihistamine (e.g. cyclizine) is generally effective.
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