see also: [[Procedural sedation]], [[Induction agents]]. [[Benzodiazepines]] See : [RCH Procedural Sedation for ward](x-devonthink-item://F6917C6B-E172-4A5C-80C1-45E0AE853A05?page=16) > [!info] > - benzodiazepines have a built-in ceiling effect that prevents them from exceeding the physiologic maximum of GABA inhibition. > - The low toxicity of the benzodiazepines and their corresponding clinical safety is attributed to this limitation of their effect on GABAergic neurotransmission > - All benzodiazepines are highly lipid soluble and are highly bound to plasma proteins, especially albumin. Hypoalbuminemia owing to hepatic cirrhosis or chronic renal failure may increase the unbound fraction of benzodiazepines, resulting in enhanced clinical effects produced by these drugs. > - > [Category:: sedetive] > [Class:: benzo] - The short duration of action of a single dose of midazolam is due to its lipid solubility, leading to rapid redistribution from the brain to inactive tissue sites as well as rapid hepatic clearance. - Midazolam, like other benzodiazepines, produces decreases in CMRO2 and cerebral blood flow analogous to barbiturates and propofol. - Cerebral vasomotor responsiveness to carbon dioxide is preserved during midazolam anesthesia **Onset:** 1-3 minutes, variable **half-life:** 1-4 hours . Similar Vd as diazepam **Key issues:** - caution in liver failure and COPD pts - The most significant side effect of midazolam when used for sedation is depression of ventilation caused by a decrease in the hypoxic drive, particularly in concert with other anesthetic drugs. - Midazolam produces dose-dependent decreases in ventilation with 0.15 mg/kg IV producing effects similar to diazepam, 0.3 mg/kg IV - Patients with ==COPD== experience even greater midazolam-induced depression of ventilation - Patients with chronic obstructive pulmonary disease may also manifest exaggerated depression of ventilation following administration of benzodiazepines to produce sedation. It is important to appreciate that ==increasing age== greatly increases pharmacodynamic variability and is associated with generally increased sensitivity to the hypnotic effects of midazolam - In healthy volunteers, midazolam alone produced no ventilatory depressant effects, whereas the combination of midazolam, 0.05 mg/kg IV, and fentanyl, 2 μg/kg IV, resulted in arterial hypoxemia and/or hypoventilation - Cardiac output is not altered by midazolam, suggesting that blood pressure changes are due to decreases in systemic vascular resistance. - benzodiazepines may be beneficial in improving cardiac output in the presence of congestive heart failure. - The use of midazolam for induction never gained widespread use; loss of consciousness, even with high doses, is slow and unreliable, and hemodynamic response to endotracheal intubation is not reliably blunted. Midazolam, 0.2 mg/kg IV, for induction of anesthesia produces a greater decrease in systemic blood pressure and increase in heart rate than does diazepam, 0.5 mg/kg IV. > Long-term IV administration of midazolam (loading dose 0.5-4 mg IV and maintenance dose 1-7 mg/hour IV) to produce sedation in intubated patients results in relative ==saturation of peripheral tissues== with midazolam and clearance from the systemic circulation becomes less dependent on redistribution into peripheral tissues and ==more dependent on hepatic metabolism==. In addition, pharmacologically active metabolites may accumulate with prolonged IV administration of the parent drug. # Dose ## procedural sedation - 1 -2.5mg IV / 0.05-0.1mg/kg (TBW) - 0.5mg in elderly / 0.05 mg/kg Rpt dosing 0.5-2.5mg Q2-3 min (longer interval for elderly) - onset in 3-5 min **Advantages** - longer periods of sedation - Less hypotension than propofol **Disadvantages** - no analgesia - Increased cardio/resp depression when combined with opiates ## paediatric seizure see: [[Seizure (paediatric)]] IV/IO/IM: 0.15mg/kg IN: 0.3 mg/kg ## RSI induction 0.1 - 0.3 mg/kg usually onset too long (1-2 min) for emergency RSI; can cause some hypotension midaz + fent can be considered in shocked or frail/elderly patients ## ongoing sedation infusion 1-4 mcg/kg/min 0.06 - 0.24 mg/kg/hour (elsewhere 0.02 - 0.2 mg/kg/hour) ## paediatric sedation - oral 0.5mg/kg max 15 mg - intranasal/buccal 0.3mg/kg max 10mg # intranasal midazolam Intranasal midazolam dose Use 5mg/mL midazolam for injection \>4 month (corrected age) 0.2- 0.4 mg/kg up to maximum 10mg (Repeat in 5–15 minutes if required); usually start 0.3mg/kg IN