Mount Sinai Expert Guides. Группа авторов
minutes.Elimination half‐life 2–4 hours.CSHT is 200 minutes after a 6 hour infusion, and 300 minutes or greater after a 12 hour infusion (this can increase unpredictably in multiorgan failure).
Drug‐specific side effects:Chest wall rigidity: a very uncommon side effect of synthetic opioids that can be complicated by glottic closure and trismus. Appears somewhat related to dosage, rapidity of administration, extremes of age, presence of critical illness, and use of antidepressant medications. Can render a patient unable to ventilate. Requires immediate reversal with naloxone and preparations for emergent intubation with a neuromuscular blocker. If no further complications are noted (e.g. negative pulmonary pressure edema due to closed glottis), extubation can be attempted within minutes of cessation of rigidity and neuromuscular blockade. This is not an allergic reaction and does not preclude the patient from receiving this analgesic agent in the future.
Recommended doses:Bolus: 0.35–0.5 μg/kg IV every 0.5–1 hour.Infusion: 0.7–10 μg/kg/h.PCA: bolus 15–75 μg, lockout interval 3–10 minutes.
Hydromorphone
Pharmacology:Semisynthetic opioid.Hepatic metabolism, renal elimination.No active metabolites.Onset of action 5–15 minutes, duration of effect 3–4 hours.Elimination half‐life 2–3 hours.
Drug‐specific side effects:Some histamine release with administration.
Recommended doses:Bolus: 0.2–0.6 mg IV every 1–2 hours.Infusion: 0.5–3 mg/h.PCA: bolus 0.1–0.5 mg, lockout interval 5–15 minutes.
Morphine
Pharmacology:Poorly lipid soluble.Hepatic metabolism with active metabolite morphine‐6‐glucuronide.Renally eliminated.Onset of action 5–10 minutes, duration of effect 4–5 hours.Elimination half‐life 3–4 hours.
Drug‐specific side effects:Accumulation can occur in renal failure.Can cause clinically significant histamine release.
Recommended doses:Bolus: 2–4 mg IV every 1–2 hours.Infusion: 2–30 mg/h.PCA: bolus 0.5–3 mg, lockout interval 10–20 minutes.
Methadone
Pharmacology:Synthetic opioid with antagonism of NMDA receptors along with usual agonism of opioid receptors.Hepatic metabolism and renal elimination.No active metabolites.Onset of action 10–20 minutes, duration of effect 6–8 hours.Elimination half‐life 15–60 hours.
Drug‐specific side effects:QTc prolongation: ECG monitoring is recommended while using this drug.
Recommended doses:Bolus: 10–40 mg every 6–12 hours.Infusion: not recommended.
Benzodiazepines
Associated with increased rates of delirium and PTSD.
Anxiolytic, amnestic, and anticonvulsant.
GABA agonist.
No analgesic properties.
Synergistic respiratory depression with opioids.
Can cause hypotension.
Hepatic metabolism and renal elimination.
Midazolam
Pharmacology:High lipid solubility.Active metabolites.Only benzodiazepine formulation without propylene glycol as solvent.Metabolized by several cytochrome P450 enzymes.Onset of action 2–5 minutes, duration of effect 1–2 hours.Elimination half‐life 3–11 hours, significant CSHT.Cessation of effect is due to redistribution.
Drug‐specific side effects:Renal elimination of active metabolites.
Recommended doses:Bolus: 0.01–0.05 mg/kg.Infusion: 0.02–0.1 mg/kg/h.
Lorazepam
Pharmacology:No active metabolites.Onset of action 15–20 minutes, duration of effect 1–2 hours.Elimination half‐life 3–11 hours.
Drug‐specific side effects:Typical solutions contain propylene glycol that can cause metabolic acidosis and acute kidney injury when run as an infusion. A serum osmolar gap greater than 10–12 mOsm/L suggests propylene glycol toxicity.
Recommended doses:Bolus: 0.02–0.04 mg/kg (maximum dose 2 mg) every 2–6 hours as required.Infusion (generally not recommended): 0.01–0.1 mg/kg/h (maximum dose <10 mg/h).
Diazepam
Pharmacology:Active metabolites.Onset of action 2–5 minutes IV, peak effect 1‐2 hours, duration of effect variable but typically 4–6 hours.Can be given per rectum for seizure treatment if no intravenous access.Elimination half‐life 20+ hours due to active metabolites.
Drug‐specific side effects:Respiratory depression.Phlebitis.Uses propylene glycol as solvent.Accumulation of metabolites in renal failure.
Recommended doses:Bolus: 5–10 mg IV.PRN dosing: 0.03–0.1 mg/kg every 0.5–6 hours.Rectal dose for seizures: 0.2 mg/kg seizures, every 4–12 hours as required, status epilepticus 0.5 mg/kg bolus and 0.25 mg/kg every 10 minutes as required.
Other sedatives
Propofol
Pharmacology:Predominantly agonist at GABA receptor.Hypnotic, antiemetic, and anticonvulsant.No analgesic properties.98% protein bound.No active metabolites.Onset of action 1–2 minutes, duration of effect 5–10 minutes.Propofol is delivered in a fat emulsion that provides 1.1 kcal/mL. This should be considered when adjusting enteral and parenteral nutritional requirements.
Side effects:Vasodilation and hypotension.Myocardial depression.Respiratory depression.Pancreatitis.Propofol infusion syndrome:A potentially lethal syndrome marked by metabolic acidosis, hypertriglyceridemia, and hypotension refractory to vasopressors.Believed due to mitochondrial dysfunction.Treatment is cessation of infusion and supportive.Associated with prolonged infusions of greater than 70 μg/kg/min.Incidence of propofol infusion syndrome 1%, mortality 33%.
Recommended doses:Bolus: 0.1–0.3 mg/kg slowly.Infusion: 5–50 μg/kg/min.
Dexmedetomidine
Pharmacology:Alpha‐2 receptor agonist.Minimal respiratory depression.Hypnotic and analgesic properties.No active metabolites.Onset of action after loading dose 5–10 minutes.
Side effects:Hypertension: often associated with loading doses.Hypotension: often associated with loading doses.Bradycardia.
Recommended doses:Loading dose: 1 μg/kg over 10 minutes.
Infusion: FDA approved for 0.2–0.7 μg/kg/h for up to 24 hours; reports have shown safety with maximum infusion 1.5 μg/kg/h for up to 1 month.
Miscellaneous:No proven benefit to delirium.
Ketamine
Pharmacology:NMDA antagonist.Hypnotic and analgesic.Active metabolite norketamine.There should be no expectation of decreased opioid use or rates of delirium after a single intraoperative dose of ketamine.Onset of action 30–40 seconds.Elimination half‐life 2–3 hours.
Side effects:Increased salivation.Potential for increased intracranial pressure