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 (ICP)Potential for sympathetic discharge.Hallucinations: can be attenuated by simultaneous administration of benzodiazepine.Negative inotropy: may be harmful in heart failure patients; further research is warranted.
Recommended doses:Bolus: 0.1–0.5 mg/kg IV.Infusion: 0.05–0.4 mg/kg/h.
Reading list
1 Barr J, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 2013; 41(1):263–306.
2 Devlin JW, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med 2018; 46:e825–73.
3 Joffe AM, McNulty B, Boitor M, Marsh R, Gélinas C. Validation of the critical‐care pain observation tool in brain‐injured critically ill adults. J Crit Care 2016; 36:76–80.
4 Khan BA, et al. Comparison and agreement between the Richmond Agitation‐Sedation Scale and the Riker Sedation‐Agitation Scale in evaluating patients’ eligibility for delirium assessment in the ICU. Chest 2012; 142(1):48–54.
5 Kotifs K, Zegan‐Baranska M, Szydlowski L, Zukowski M, Ely EW. Methods of pain assessment in adult intensive care unit patients – Polish version of CPOT (Critical Care Pain Observation Tool) and BPS (Behavioral Pain Scale). Anaesthesiol Intensive Ther 2017; 49(1):66–72.
6 Parker AM, Sricharoenchai T, Raparla S, Schneck KW, Bienvenu OJ, Needham DM. Posttraumatic stress disorder in critical illness survivors. Crit Care Med 2015; 43(5):1121–9.
7 Patanwala AE, Martin JR, Erstad BL. Ketamine for analgosedation in the intensive care unit: a systematic review. J Intensive Care Med 2017; 32(6):387–95.
8 Payen J, et al. Assessing pain in critically ill sedated patients by using a behavioral pain scale. Crit Care Med 2001; 29(12):2258–63.
9 Reade MC, et al. for the DahLIA Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Effect of dexmedetomidine added to standard care on ventilator‐free time in patients with agitated delirium: a randomized clinical trial. JAMA 2016; 315(14):1460–8.
10 Turunen H, et al. Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation. Crit Care 2015; 19(1):67.
Additional material for this chapter can be found online at: www.wiley.com/go/mayer/mountsinai/criticalcare
This includes multiple choice questions.
CHAPTER 3 Vascular Access
