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By Brenda T. Pun, MSN, RN, ACNP, and Jan Dunn, MSN, RN 3 HOURS Continuing Education The Sedation of Critically Ill Adults: PART 2: MANAGEMENT OVERVIEW: The prevention and treatment of pain, anxiety, and delirium in the ICU are important goals. But achieving a balance between sedation and analgesia, especially in critically ill patients on mechanical ventilation, can be challenging. Both under- and oversedation carry grave risks. Without having an agreed-upon end point for sedation, differen
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  40 AJN M August 2007 M Vol. 107, No. 8 http://www.nursingcenter.com I n2002 the Society of Critical CareMedicine (SCCM), along withthe American Society of Health-System Pharmacists, updated rec-ommendations in its clinical practice guidelines on the sustaineduse of sedatives and analgesics in adults, acknowledging thatalthough sedatives often areused in the ICU to treat anxiety andagitation, indications for their use “are not well defined.” 1 The updatedrecommendations—divided into three sections focusing on pain, seda-tion, and delirium—seek to clarify these murky waters. (The SCCM’sguidelines were graded according to the strength of the supporting evi-dence; see Grading the Recommendations, page 42.)This two-partseries examines the SCCM recommendations and currentliterature pertinent to sedation, which is used primarily to relieve anxietyand agitation. In Part1, published last month, we discussed the importanceof using reliable tools to differentiate between pain, delirium, and anxietyand agitation; their signs and symptoms may look alike, but they can havedifferent causes and requiredifferent treatments. In this article, Part 2, wepresent an algorithm for doing so and discuss specific recommendationsfor managing sedation when it’s needed to treat anxiety and agitation. MANAGING ANXIETY AND AGITATION IN THE ICU Ideally, nonpharmacologic management  should be considered first—asimplied in the SCCM’s algorithm (see Figure 1, page 44)—or at least con-currently with pharmacologic treatment, although this may be impracti-cal when the need for sedation is urgent. In some cases,nonpharmacologic therapies may be effective enough that the use of sedatives can be reduced or avoided, although we could not find any Brenda T. Pun is a project manager at Vanderbilt University Medical Center inNashville, TN, and a member of its ICU Delirium and Cognitive Impairment StudyGroup. Jan Dunn is a research coordinator at Saint Thomas Hospital in Nashville,TN. Pun has been a paid consultant for Hospira, Inc., which manufactures Precedexand SEDLine, products named in this two-partseries. The authors of this article haveno other significant ties, financial or otherwise, to any company that might have aninterest in the publication of this educational activity. Contact author: Brenda T. Pun,brenda.pun@vanderbilt.edu. Continuing Education 3 HOURS By Brenda T. Pun, MSN, RN, ACNP,and Jan Dunn, MSN, RN The Sedation of  P  ART 2:M  ANAGEMENT Critically Ill Adults: OVERVIEW: The prevention and treatment ofpain,anxiety,and delirium in the ICU are importantgoals.But achieving a balance between sedationand analgesia,especially in critically ill patientsonmechanical ventilation,can be challenging.Bothunder-and oversedation carry grave risks.Withouthaving an agreed-upon end point for sedation,different providers will likely have disparate treat-ment goals,increasing the risk of iatrogenic com-plications and possibly impeding recovery.In2002 the Society of Critical Care Medicine,alongwith the American Society of Health-SystemPharmacists,updated recommendations in its clin-ical practice guidelines for the sustained use ofsedatives and analgesics in adults.This two-partseries examines those recommendations concern-ing sedation assessment and management,aswell as the current literature.Last month,Part 1reviewed pertinent recommendations concerningpain and delirium and discussed tools for assess-ing pain,delirium,and sedation.This month,Part 2explores pharmacologic and nonpharmacologicmanagement of anxiety and agitation in the ICU. The second in a two-part series focuses on the pharmacologic and nonpharmacologic man- agement of anxiety and agitation in the ICU.  ajn@wolterskluwer.com AJN M August 2007 M Vol. 107, No. 8 41 studies that have investigated this specifically.Nonpharmacologic interventions may include oneor more of the following 2, 3 :ãestablishing a method of nonverbal communica-tion (for example, blinking or head nodding)ãusing a calm voice and gentle touch to conveyreassuranceãfrequent repositioningãusing distraction (such as listening to music,watching television)ãmaking environmental changes (such as noisereduction)ãusing complementary therapies (such as aro-matherapy and massage therapy)Although few data supporting the use of non-pharmacologic therapies for managing agitationand anxiety in the ICU are available, a few studieshave shown improved outcomes. In studies of car-diac patients and patients on mechanical ventila-tion, listening to music has been associated with alowered heart rate and arterial blood pressure,reduced anxiety, and fewer cardiac complications. 4-6 Apilot study subjecting volunteers to recorded ICUnoise in a sleep laboratory found that earplugs maypromote sleep in clinical settings. 7 Back massagewas found to promote sleep in critically ill oldermen, “lending indirect support to findings that backmassage increases relaxation” and lowers anxiety. 8       I       l       l    u    s     t    r    a     t      i    o    n       b    y      C       h    a    r       l    e    s      K    a      i    m    a    n  42 AJN M August 2007 M Vol. 107, No. 8 http://www.nursingcenter.com Although researchers found an association betweenaromatherapy and massage and improved moodand decreased anxiety,they found no link to phys-iologic stress indicators. 3 Pharmacologic management. In choosing theappropriate sedative, it’s important to understandhow each agent works and what its limitations are. The ideal  sedative has been described as one thatworks rapidly; provides anxiolysis, sedation, amnesia,or a combination of these; allows quick emergencewhen stopped; permits easy administration andadjustment of dosage; produces no active metabolites,significant adverse effects, or drug–drug interactions;and is inexpensive. 9, 10 No drug meets all these criteria.Clinicians must therefore choose a sedative accordingto the patient’s condition. The following are descrip-tions of the most commonly used sedatives. Benzodiazepines (including diazepam [Valium],lorazepam [Ativan], and midazolam [Versed]) arethe most widely used sedatives in the United States.The SCCM guidelines include the following recom-mendations (all recommendations from the SCCMguidelines used in this article are presented verba-tim) 1 :ãMidazolam or diazepam should be used forrapid sedation of acutely agitated patients.(Grade of recommendation = C)ãMidazolam is recommended for short-term useonly,as it produces unpredictable awakeningand time to extubation when infusions continuelonger than 48–72 hours. (Grade of recommen-dation = A)ãLorazepam is recommended for the sedation of most patients via intermittent iv administration Grading the Recommendations  How the SCCM guidelines were created. LevelType of evidence 1Results from a single PRCT* or from a metaanalysisof PRCTs2Results from a single PRCT or from a metaanalysis of PRCTs,in which the confidence interval for the treatmenteffect overlaps the minimal clinically important benefit3Results from nonrandomized,concurrent,cohort studies4Results from nonrandomized,historical,cohort studies5Results from case series6Recommendation based on expert opinion*PRCT = prospective,randomized,controlled trial. Nasraway SA, Jr., et al. Crit Care Med  2002;30(1):118. Reprinted withpermission. Table B. Grades of Recommendations Nasraway SA, Jr., et al. Crit Care Med  2002;30(1):118. Reprinted withpermission. GradeType of evidence AMethods strong,results consistent,PRCTs,*no heterogeneityBMethods strong,results inconsistent,PRCTs,hetero-geneity presentCMethods weak,observational studies*PRCT = prospective,randomized,controlled trial. Table A. Categories of Literature Evaluation I nthe mid-1990s the Society of Critical Care Medicine(SCCM),its affiliate the American College of Critical CareMedicine,and the American Society of Health-SystemPharmacists created a task force to develop clinical practiceguidelines on the sustained use of sedatives and analgesics incritically ill adults.A revised and updated version,oftenreferred to as “the SCCM guidelines,”was published in 2001.Because these guidelines are based on the evidence,it’sessential that the evidence be evaluated systematically.After performing a literature search,the task force reviewedrelevant studies and their reference lists,as well as abstractsfrom professional meetings.This literature,which varied widelyin quality,was first classified by its type (see Table A,at right).Each article or abstract was then critically evaluated and scoredto reflect the quality of its evidence.In doing so,the task forceconsidered “research design,patient selection,medication dose,administration route,combination treatment,test measures,statistics,and results.” 1 The SCCM guidelines include recommendations that werebased on this literature review and were graded according tothe strength and quality of the supporting evidence.This grad-ing system (see Table B,at right) was itself devised by the taskforce,which reported that it made “a substantial effort ...toadhere to the methodology for developing scientifically soundclinical practice guidelines as prescribed by the AmericanMedical Association,the Institute of Medicine,and theCanadian Medical Association.” 1 REFERENCE 1.Nasraway SA, Jr., et al. Sedation, analgesia, and neuromuscularblockade of the critically ill adult: revised clinical practiceguidelines for 2002. Crit Care Med  2002;30(1):117-8.  ajn@wolterskluwer.com AJN M August 2007 M Vol. 107, No. 8 43 cerebral blood flow, and cerebral metabolism. 1, 13 Itcan also be used in patients who areabout to beweaned from mechanical ventilation and have beenon long-term benzodiazepine therapy. Propofol canbe started while the benzodiazepine is tapered toavoid withdrawal symptoms; the rapid awakeningwith propofol helps to facilitate extubation.Adverse effects associated with propofol includedose-dependent hypotension, respiratorydepres-sion, and pain at the infusion site. 1, 10, 11 The drug isprepared in a lipid emulsion, so long-term or high-dose infusion may lead to elevated triglyceride lev-els; serumtriglyceride levels should be monitoredand the emulsion considered a caloric source. 1, 10, 11 Because the lipid emulsion can promote bacterialgrowth, strict aseptic technique and a dedicated iv catheter are essential to prevent infection. The man-ufacturers recommend that propofol infusion tub-ing and any unused product be discarded 12 hoursafter spiking the vial. If the drug is transferred toanother container before administration, any unusedproduct should be discarded and tubing changedafter six hours. To help retard the growth of microor-ganisms, the manufacturers have added preservatives.One formulation (the brand name Diprivan) containsdisodium edentate, a strong chelator of trace metals,including zinc. This manufacturer recommends aor continuous infusion. (Grade of recommenda-tion = B)Drugs in this class produce sedation and an-terograde amnesia by enhancing the effects of  γ  -aminobutyric acid (GABA), a potent inhibitoryneurotransmitter. Because of their rapid onset (twoto five minutes), midazolam and diazepam are rec-ommended for treatment of acute agitation.Because midazolam has been associated with accu-mulation and prolonged sedation in critically illpatients who are obese or in kidney failure, it’s onlyrecommended for less than 24 hours; lorazepamis recommended for longer use. 1, 11 Benzodiazepinesmay produce adverse effects, including respiratoryand cardiovascular depression, hypotension, toler-ance, physical dependence, and paradoxical agita-tion, as well as prolonged sedation and unpredictableawakening resulting from accumulation of the drugor its active metabolites. 1, 11 The use of lorazepamhas recently been reported to be an independentrisk factor for ICU patients who develop delirium,with the risk of developing delirium increasing asthe dosage increases. 12 Because benzodiazepines pose a risk of accumu-lation, adjusting the dosage of these drugs can bedifficult. It’s important to establish a dosage endpoint and to frequently reassess the patient’sneedsand adjust the dosage accordingly, especially whenadministering a benzodiazepine by continuous infu-sion. 1 For the same reason, when a benzodiazepineis given to elderly patients and patients with hepaticinsufficiency,the lowest possible starting doseshould be used and then adjusted upward asneeded. 1 Propofol (Diprivan) is a sedative–hypnotic agentused for anesthesia or sedation. The SCCM guide-lines include the following recommendations for itsuse as a sedative 1 :ãPropofol is the preferred sedative when rapidawakening (e.g., for neurologic assessment orextubation) is important. (Grade of recommen-dation = B)ãTriglyceride concentrations should be monitoredafter two days of propofol infusion, and totalcaloric intake from lipids should be included inthe nutrition support prescription. (Grade of rec-ommendation = B)How propofol works isn’t completely under-stood, but it’sbelieved to enhance GABA’saffinityfor its receptors, much like the benzodiazepines.Because propofol has a very rapid onset (one to twominutes) and its concentration in plasma fallsquickly once the drug is discontinued, it’s the seda-tive recommended when rapid awakening is needed(for example, for neurologic assessment or extuba-tion). 1 Propofol is a useful drug for patients withneurologic injury; it decreases intracranial pressure,  ANote on Pain Control  A  sone review has stated,“failure to recognize thatpain frequently leads to agitation may result in exces-sive administration of sedatives.” 1 And it’s known that ade-quate pain management often reduces the need forsedation. 1 Recent reports further suggest that,comparedwith traditional sedation (benzodiazepines plus analgesicsfor pain),narcotics-based sedation (such as fentanyl or mor-phine) may result in improved patient outcomes. 2,3 Once thepatient’s pain is controlled adequately,sedative agentsshould be administered as needed.(For more information onensuring adequate pain relief in patients who can’t provideareport of pain,see Pain Control, “No Self-Report MeansNo Pain-Intensity Rating,”October 2005.) REFERENCES 1.Kress JP, et al. Sedation and analgesia in the intensive careunit. Am J Respir Crit Care Med  2002;166(8):1024-8.2.Breen D, et al. Decreased duration of mechanical ventilationwhen comparing analgesia-based sedation using remifen-tanil with standardhypnotic-based sedation for up to 10days in intensive care unit patients: a randomised trial[ISRCTN47583497]. Crit Care 2005;9(3):R200-10.3.Pandharipande P, Ely EW. Narcotic-based sedation regimensfor critically ill mechanically ventilated patients. Crit Care 2005;9(3):247-8.
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