Sedative Drugs in Procedural Sedation

Sedative drugs in procedural sedation produce anxiolysis, amnesia and a depressed level of consciousness so that procedures can be done outside the operating theatre. The aim is the lightest depth that gives adequate conditions, with analgesia added separately when the procedure is painful. Hypoventilation, airway obstruction and hypotension are the main hazards, and depth can deepen without warning.

Depth of sedation. Minimal (responds normally to voice); moderate (purposeful response to voice or light touch, airway and ventilation adequate); deep (responds only to repeated or painful stimulus, airway may need help); general anaesthesia (unrousable). The operator must be able to rescue a patient from one level deeper than intended.

Classes and mechanism. Benzodiazepines (midazolam) and propofol enhance GABA-A receptor activity. Ketamine blocks NMDA receptors and gives dissociation with analgesia. Dexmedetomidine is an alpha-2 agonist. Opioids (fentanyl) add analgesia and synergistic respiratory depression. Nitrous oxide 50% in oxygen gives light sedation and analgesia.

Pharmacokinetics. Intravenous onset is 1 to 3 minutes for midazolam, 30 to 60 seconds for propofol and ketamine, 5 to 10 minutes for dexmedetomidine. Propofol and ketamine wear off within 5 to 15 minutes; midazolam and dexmedetomidine last longer.

Etomidate. 0.1 to 0.15 mg/kg intravenously is used for cardioversion and some short procedures when haemodynamics are fragile; myoclonus and adrenal suppression limit wider use.

Children. Midazolam 0.5 mg/kg orally (maximum 20 mg) 20 to 30 minutes before the procedure, or 0.2 to 0.3 mg/kg intranasally, or 0.05 to 0.1 mg/kg intravenously titrated. Ketamine 1 to 2 mg/kg intravenously or 4 to 5 mg/kg intramuscularly. Dexmedetomidine 2 to 3 micrograms/kg intranasally is used for imaging in some centres.

Reversal. Flumazenil 0.2 mg intravenously, repeated to a total of 1 mg; naloxone 40 to 100 micrograms intravenously, repeated, for opioid-induced hypoventilation. Both wear off sooner than the drug being reversed, so resedation can occur.

• First-line. Propofol for brief painful procedures with trained staff (cardioversion, endoscopy, joint reduction); ketamine for painful procedures in children and in hypotensive or hypoxic-risk patients; midazolam for anxiolysis and for imaging.
• Alternative. Dexmedetomidine for imaging and noninvasive procedures when respiratory preservation is needed; nitrous oxide for short procedures in cooperative patients; etomidate for cardioversion in unstable patients.
• Specialist. Combined propofol and ketamine; sedation in patients with difficult airway or advanced cardiopulmonary disease, which needs an anaesthetist.
• Emergency. Ketamine 1 to 2 mg/kg intravenously or 4 to 5 mg/kg intramuscularly for painful emergency procedures and for agitation when other measures have failed.

Selection. Match depth, analgesia and duration to the procedure; use one primary agent and avoid stacking benzodiazepine, opioid and propofol; give analgesia (fentanyl or local anaesthetic) for painful steps; prefer ketamine where monitoring is limited and the airway is at risk of obstruction from other agents.

Contraindications.

• No trained person dedicated to the patient, no monitoring, no oxygen, suction or airway equipment.
• Unprotected airway with full stomach and decreased consciousness (relative; weigh urgency against risk).
• Ketamine: severe hypertension, eclampsia, active psychosis, raised intracranial pressure with uncontrolled airway, and known airway disorders with laryngospasm risk (relative).
• Propofol: severe hypotension, egg or soya allergy as a caution.
• Midazolam: acute narrow-angle glaucoma, severe respiratory failure, sleep apnoea (relative).
• Dexmedetomidine: advanced heart block.

Serious adverse effects. Hypoxia, apnoea, airway obstruction, aspiration, hypotension, bradycardia, laryngospasm (ketamine, uncommon), emergence delirium, paradoxical agitation (midazolam, particularly in children and older adults), propofol injection pain, nausea and vomiting after ketamine.

Major interactions. Opioids with benzodiazepines or propofol multiply respiratory depression; CYP3A4 inhibitors (clarithromycin, azoles, ritonavir, diltiazem) prolong midazolam; alcohol and other sedatives add; beta-blockers with dexmedetomidine add to bradycardia.

Common prescribing errors.

• Full adult dose in older or frail patients.
• Repeating doses before the previous dose has peaked.
• Giving an opioid and a benzodiazepine together without extra monitoring.
• Starting the procedure before sedation has taken effect.
• Missing fasting and aspiration assessment.
• Discharging while still drowsy.

Special groups.

• Pregnancy: use the lowest dose with left lateral tilt after 20 weeks; avoid prolonged benzodiazepine use near term.
• Breastfeeding: compatible once the mother is awake and alert.
• Children: weight-based doses; sedation depth moves faster; ketamine preferred for painful procedures; avoid unmonitored oral sedation at home.
• Older adults: halve initial doses and titrate slowly.
• Kidney: little effect except accumulation of midazolam metabolites in prolonged use.
• Liver: prolonged midazolam and dexmedetomidine effect; reduce doses.
• East Africa: ketamine is often the only practical sedative in district facilities; capnography is rarely available, so use continuous pulse oximetry, constant observation of chest movement and a bag-valve-mask at hand.

Monitoring. Continuous pulse oximetry and heart rate; blood pressure every 3 to 5 minutes; capnography whenever available; sedation score (for example, responds to voice or not); recovery until the patient is awake, oriented to baseline and able to protect the airway, with an escort for discharge.

Referral and escalation. Apnoea or airway obstruction not corrected by repositioning and bag-valve-mask ventilation; unplanned deep sedation; persistent hypotension; anaphylaxis; any patient with predicted difficult airway or severe cardiopulmonary disease should have sedation by an anaesthetist.

Comparison with alternative classes. Sedation avoids the airway control and recovery time of general anaesthesia but gives less predictable depth. Regional or local anaesthesia gives analgesia without respiratory depression and should be used wherever it suffices.