CHOICE OF SEDATION FOR CRITICALLY ILL …

1 Advanced Studies inMedicine 343 ABSTRACTB ecause no single, ideal sedative exists, theclinician must take care to select the best agentto ensure effective SEDATION while minimizingside effects and maintaining a good cost-effec-tiveness profile. This article discusses the mostcommonly used sedatives and assesses theirusefulness and effectiveness in the clinical set-ting, citing the latest guidelines provided theSociety of Critical Care Medicine.(Advanced Studies in Medicine2002;2(9):343-349)The ideal intensive care unit (ICU) sedativewould reduce stress and provide anxioly-sis, analgesia, and amnesia, as well asimprove tolerance of ventilatory supportand nursing interventions.

2 In addition, itwould have little effect on cardiovascular function; fastonset; fast offset with minimal respiratory depression,if possible; and have no active metabolites. This drugwould have no interactions with other medications; nopain on injection; no tolerance or withdrawal; be safefor all ages and have no age-related changes in phar-macokinetics; and be cost effective. Unfortunately, thisideal sedative does not there is no ideal sedative, evidence-basedmedicine must be used to determine or choose a seda-tive regimen for patients; however, this can be diffi-cult. Few randomized control studies have beenconducted comparing different sedative agents. Insome cases, the results of these studies have beenunconvincing, as pharmacology of the drugs tends tochange with duration of infusion, and studies may notreflect actual clinical use.

3 Additionally, sedatives arefrequently used in conjunction with analgesics; choiceof analgesic agent is based on the patient s individualneeds and must be considered in the sedative recently revised guidelines by the AmericanCollege of Critical Care Medicine (ACCM) provideparameters for the use of analgesics and sedatives inthe ACCM guidelines define analgesia as theblunting or absence of sensation of pain or noxiousstimuli. Inadequate pain relief can have a number ofconsequences, including agitation, and can evoke astress response that is characterized by tachycardia,increased myocardial oxygen consumption, hyperco-agulability, immunosuppression, and persistent catab-olism.

4 The concomitant use of analgesics and sedativescan relieve agitation and lessen the stress analgesics commonly used in the ICU includefentanyl, morphine, and hydromorphone. OPIOIDSS election of an opioid is based upon its pharma-cology and potential for adverse of an ideal agent would include rapidonset, ease of titration, lack of accumulation, andlow cost. PROCEEDINGSCHOICE OF SEDATION FOR CRITICALLY ILL PATIENTS:A RATIONAL APPROACH* Louis Brusco, Jr, MD*This article is based on a presentation given by Dr Brusco at a satellite symposium held at the Society ofCritical Care Medicine, January 27, correspondence to: Louis Brusco, Jr, MD, St.

5 Luke s-Roosevelt Hospital Center, Department of Anesthesiology,1111 Amsterdam Avenue, New York, NY 2, No. 9 June 2002 PROCEEDINGSA dverse events as a result of the use of opioidsoccur frequently in the ICU and may include negativeeffects on respiratory rate, hemodynamic function, thecentral nervous system, and the gastrointestinal sys-tem. Hypotension may occur in patients who arehemodynamically unstable, hypovolemic, or thosewith elevated sympathetic tone. Myoclonus and mus-cle rigidity may occur with high-potency opioids andmay affect ventilatory ,2 FENTANYLF entanyl is a synthetic opioid with a rapid onsetand short duration of action. It may be delivered byintermittent intravenous administration, continuousinfusion, or transdermal administration.

6 It has no sig-nificant metabolites. Transdermal use is not recom-mended for acute relief due to a 12- to 24-hour delayto peak effect. Repeated dosing of a drug may cause accumulationand prolonged ,2 With prolonged infusion, thehalf-life increases dramatically from 30 to 60 minutesto 9 to 16 also exhibits tachyphylax-is, with larger volumes of the drug necessary over time,which may result in an increased recovery period fol-lowing prolonged is more hemo-dynamically stable than morphine; however, it stillmay result in hypotension due to suppression ofendogenous sulfate is a prototypical opioid with alonger duration of action than fentanyl. It is adminis-tered in intermittent doses.

7 Significant metabolitesinclude morphine-3 and morphine-6 has a half-life of 2 to 3 hours in healthyadults, but is increased in patients with severe cirrho-sis or burns. Septic shock and renal disease decreaseclearance, and end-organ disease significantly affectsmetabolism of the ,2 Vasodilation may result in hypotension and theactive metabolites may result in prolonged SEDATION inpatients with renal morphine-stimu-lated histamine release may result in allergic reactionsand cardiovascular is a high-potency, semisyntheticopioid that may be administered in oral, rectal, andparenteral forms. It is inexpensive, has a half-life ofapproximately 2 to 3 hours, and is commonly used forpatients with severe long-term pain.

8 Hydromorphone-3-glucuronide is the active metabolite, but it is notclinically ,2 While the duration of action is similar to mor-phine, it does not stimulate histamine is a potent respiratory depressant"Rapid onset of action"Easily titratable level of adequate SEDATION "Short acting, allowing patient assessment, rapid recovery fol-lowing discontinuation, easy weaning from mechanical ventila-tion, and early extubation"No or few adverse effects"No anaphylaxis or allergic reaction"No nausea, vomiting, or phlebitis"No or minimal interaction with other drugs"Minimal metabolism; not dependent on normal hepatic, renal,or pulmonary function"Minimal respiratory depression"Minimal effect on cardiovascular function"No pain on injection"No active or toxic metabolites"No suppression of cortisol production by the adrenal cortex"No or minimal interactions with other commonly prescribedICU drugs"Ease of administration"Lack of accumulation with prolonged administration"Does not promote growth of pathogens"No tolerance and withdrawal symptoms"Cost effective"Easily prepared and long shelf life"Safe for all ages with no age-related changes in pharmacokinetics"Provides facilitation of ventilator synchrony and the perfor-mance of various procedures and nursing interventions"Lack of abuse potentialTable 1.

9 Characteristics of the Ideal SedativeData from references Studies inMedicine 345 PROCEEDINGSand may accumulate in cases of renal failure, resultingin neuroexcitation and cognitive states it is less effective and has greater toxi-city than other ,2 SEDATIVEHYPNOTICSE fforts to reduce anxiety in the ICU may includefrequent reorientation, maintenance of patient com-fort, provision of adequate analgesia, and optimizationof the therapy often is used asan adjunct to these measures and frequently is essentialas a part of the care plan in order to maintain patientsafety and comfort. SEDATION of mechanically ventilat-ed patients frequently is medically necessary. Table 1outlines characteristics of the ideal , the ideal sedative does not exist,and therapeutic CHOICE should be based upon individ-ual patient needs.

10 PROPOFOLP ropofol is ultra short acting following a bolus doseand short-term infusion. Its rapid onset and offset ofaction is particularly useful for the short-term sedationof 3 classes of patients: Short-term intubated patients, including: Surgical patients Asthmatics Drug overdose patients Any patient with an anticipated quick extubation Patients with changing neurologic status requir-ing frequent neurological evaluation The elderlyPropofol is a complex drug with 3 half-lives. The half-life, or distribution of the drug from the blood tothe tissues following administration, is 2 to 3 half-life, or the elimination half-life, rangesfrom 30 to 60 minutes (Figure). The half-life, or ter-minal half-life during which the drug is eliminatedfrom tissue fat, ranges from 300 to 700 time following short-term administration isapproximately 15 minutes; however the duration ofaction is prolonged after infusion exceeding 72hours,11resulting in a wake-up time of 30 to 60 min-utes.