Treating Agitation With Dexmedetomidine in the ICU

Treating AgitationWith Dexmedetomidinein the ICUJeanne Boyer, RN, MSN, CCRN, ACNP

Patients in the intensive care unit frequently experience delirium,

anxiety, and agitation, with a variety of treatments used. This article

discusses the role of an !-adrenoceptor agonist, dexmedetomidine, and

its clinical relevance and advantages for the agitated patient.

Keywords: Agitation, Anxiety, Dexmedetomidine, Sedation

[DIMENS CRIT CARE NURS. 2009;28(3):102/109]

The intensive care unit (ICU) can be an uncomfortable,fear-provoking environment for many patients. Fre-quently, they experience delirium, anxiety, and agita-tion. In addition, patients may be subjected to untreatedor intractable pain, invasive procedures, prone position-ing, sleep deprivation, or adverse drug effects.

Untoward effects of their anxiety and agitationinclude difficulty breathing, patient-ventilator dyssyn-chrony, hypertension, and tachycardia, as well as com-bative behavior.1 Consequently, in addition to receivinganalgesics, sedatives are commonly required to reduceagitation and anxiety.

The Joint Commission on Accreditation of Health-care Organizations (JCAHO) set standards for monitor-ing pain and anxiety assessment.2 Because sedation is anessential component of therapy in the ICU, JCAHO hasnow required scales for such, with the same competencein assessment and monitoring being expected. In 2002,the Society of Critical Care Medicine (SCCM), alongwith the American Society of Health-System Pharma-cists, updated clinical practice guidelines for the con-tinued use of sedatives.3 These practice guidelinesestablished preferences for sedation in providing thecalmest, least agitated, and easily aroused patients. Min-imizing agitation and anxiety has been shown to reduceICU length of stay.4

Dexmedetomidine, a selective !2-adrenoceptoragonist, is an effective sedative agent for critically ill

patients. The purpose of this article was to discuss theuse of dexmedetomidine as an alternative to currentcommonly used therapies for managing agitation incritically ill patients.

INCREASING AGITATION IN THE ICUAgitation is defined as an increased irritable tensestate that can lead to confusion, excessive psychomotoractivity, and hostility.5 It can have an acute onset or aslow progression lasting as long as it is not treated. Inthe ICU, agitation represents a sign of an unaddressedhealth issue. When it lasts for hours, changes inconsciousness may produce delirium.

Patients in the ICU experience anxiety and/or agi-tation for the partial reason that they are placed in aforeign environment. They are then further subjected toconfinement to a bed while connected to wires, tubes,and machines. Patients experience stress from a lack ofself control, anxiety, and fear. The patient’s perception ofhis or her general health, type of surgery and anesthesiareceived, postoperative pain, and disorientation all influ-ence agitation and anxiety.4 The uncertainty about theirfuture with a loss of independence and a possible fear ofdeath further contribute to anxiety and agitation. Feelingsof helplessness, pain, confusion, and memory loss withsleep deprivation aggravate agitation and anxiety.4

Already known with pain, anxiety in postsurgicalpatients has been shown to impair immune responses.6

102 Dimensions of Critical Care Nursing Vol. 28 / No. 3

Treating Agitation With Dexmedetomidine in the ICU

9Copyright @ 200 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Care providers need to ensure adequate sedation asthese surgical patients recover from general anesthesia.Certain medications commonly used in the ICU, forexample, zolpidem and furosemide, have been shown tocontribute to agitation.6 Fluid and electrolyte imbal-ances and temperature fluctuations in the environmentare also contributors.6 Alarms, lights, and environ-mental noise will also impact the patient’s degree ofstress.

CONSEQUENCES OF AGITATION ANDSEDATION ON THE ICU PATIENTAgitation and delirium in the ICU patient, whiletriggering a cascade of increased requirements for relief,are associated with prolonged hospitalizations.7 Inad-equate treatment of agitation initiates the physiologicalstress response resulting in tachycardia, hypertension,and hyperglycemia, all of which contribute to increasedmortality and morbidity in critically ill patients. Weknow that these responses are primarily mediatedthrough the autonomic nervous system. When thecortex of the brain perceives a threat, the adrenal glandsare stimulated to release epinephrine. Respiratory ratesincrease and become shallow, the heart rate increases,and blood pressure is elevated. Blood is shifted awayfrom the stomach, and glycogenolysis is accelerated withresulting elevated glucose levels. Stress ulcers occur froman increase in gastric acid production.

If not adequately comforted, restlessness and im-paired attention with poor concentration will be seen inthe anxious and agitated ICU patient. Inappropriate neu-rological assessments can occur from a lack of patientcooperation as a result of fatigue and sleep disturbances.Recent studies reveal that patients in the ICU sleep lessthan 2 hours per day.8 Using adequate sedation medi-cations must be included in the ICU nurses arsenal ofabilities to prevent the somatic effects of tachycardia,hypertension, hyperventilation, tremors, diaphoresis, andpalpitations, thus further preventing the secondary behav-ioral and cognitive responses of agitation and anxiety.7

DIAGNOSIS AND TREATMENT OFACUTE AGITATIONNurses frequently identify agitation when patientsexhibit incomprehensible speech, inappropriate scream-

ing, and dysfunctional behavior such as searching theirbed for escape routes without acknowledging theirsafety or are unable to communicate appropriately andbecome aggressive with hitting or kicking. A pastiche oftherapeutic approaches has been shown to alleviatestress and anxiety in critically ill patients. Nonpharma-cological techniques, which should be considered first,include repositioning and implementing Bsleep hours[and family support at the bedside.9 When the need forsedation becomes more, pharmacological therapies willinclude opioid narcotics, benzodiazepines, and barbitu-rates. Often administered concomitantly, they have asynergic effect and are beneficial in this patient pop-ulation.

The central motivation for sedation is to minimizephysiological stress rooted by neurosis or psychosisfrom untreated anxiety and agitation. Patients who haveadequate sedation should also be free of respiratorydepression, anxiety, and pain; are easily aroused to theirsurroundings; and hemodynamically stable. The phar-macological agent should have a rapid onset and shorthalf-life, be easily titrated, and lack serious side effects.9

Manifestations of pain, delirium, anxiety, andagitation are similar; however, they have differentetiologies and require different interventions. Therefore,the initial step in the diagnostic evaluation is to draw onreliable assessment tools. Critical care clinicians haveused various assessment tools in an effort to complywith JCAHO sedation requirements. The use of anyscale enables reaching targeted goals for adequatesedation while maintaining consistency among users.The Ramsay Sedation Scale and the Riker’s Sedation-Agitation Scale are 2 common types, with the former themost widely used in many ICUs. The optimal goal withthis scale is for the patient to score a 3 (see Table 1).10

The goal is a 2 with the Riker’s Sedation-Agitation Scale(see Table 2).10

Commonly used pharmacological agents for seda-tion include propofol, opioids, benzodiazepines, andbarbiturates. Each of these agents is associated withadverse side effects, including potential prolongation of

TABLE 1 Ramsay Level of Sedation Scale9

6 Subject asleep, no response

5 Subject asleep, sluggish response to light tap

or loud auditory noise

4 Subject asleep, but with brisk response to light

tap or loud auditory noise

3 Subject responds to commands

2 Subject cooperative, oriented, tranquil

1 Subject anxious, agitated, or restless

Care providers need to ensure adequate sedation as these surgical

patients recover from general anesthesia.

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the ICU stay (see Table 3). Each of these agents alsovaries in pharmacokinetics, an important considerationwhen treating acute agitation.

Propofol (Diprivan), mainly used in the operatingarena for induction or maintenance of general anesthesia,is a potent sedative and hypnotic anesthetic. It is titrated todesired clinical effects via continuous intravenous (IV)infusion. It is hypothesized that it resembles benzodiaze-pines with enhancing +-aminobutyric acid (GABA), acompelling inhibitory neurotransmitter, affinity for itsreceptors. It can provide conscious as well as unconscioussedation. Its rapid onset of action (30-45 seconds)facilitates titration and minimizes oversedation. Onepharmacokinetic mechanism propofol has is a weakanalgesic effect at hypnotic concentrations. In approxi-mately 50% of patients, unconsciousness is reached at 3.32g/mL.11 To suppress all movements, greater than 12 2g/mL is required.11 Hypotension and respiratory depressionare adverse effects with higher doses.12

Long-term use or ICU sedation makes monitoringtriglycerides a necessity. Because the drug is in a lipidemulsion, after 2 days of infusion, triglycerides can beelevated, and its caloric intake should be included in thenutrition prescription.11 Lidocaine is often administeredbefore propofol because of pain experienced with initialinfusion. Manufacturers recommend changing the tubing

and infusion every 12 hours because of the propensity forbacterial growth with the lipid emulsion.11

Additional disadvantages of propofol include unto-ward problems such as chelation of trace metals, espe-cially zinc, or allergic reactions in asthmatics as a result ofpreservatives added to propofol.3 High-dose propofolcan cause Bpropofol infusion syndrome,[ which resultsin the development of cardiac and renal failure, rhab-domyolysis, and severe metabolic acidosis.12 Therefore,propofol for agitation in the ICU is more or less a sec-ondary resort. Propofol is superior for anesthesia goals.

Like propofol, benzodiazepines enhance the inhib-itory tone of GABA receptors, but they are usually givenin combination with an opioid, providing a synergisticsedative effect. They also have a rapid central nervoussystem (CNS) onset of action (2-5 minutes).9,13 Theyprovide relief of anxiety at lower doses than if justrequired for sedation. Lorazepam (Ativan), diazepam(Valium), and midazolam (Versed) are the more com-mon drugs used as sedative agents in the United States.9

According to the SCCM, midazolam is recommendedfor short-term use only because of its unpredictableawakening time.14 The SCCM also recommends midazo-lam and diazepam for rapid sedation.14 Because midazo-lam has an accumulation effect, lorazepam is preferred forintermittent or a longer continuous infusion.14 It also has a

TABLE 2 Riker Sedation-Agitation Scale

Score Term Descriptor

7 Dangerous agitationVpulling endotracheal tube, trying to remove catheters, climbing over bedrail, striking at staff,

thrashing side-to-side

6 Very agitatedVrequiring restraint and frequent verbal reminding of limits, biting ETT

5 AgitatedVanxious or physically agitated, calms to verbal instructions

4 Calm and cooperative calmVeasily arousable, follows commands

3 SedatedVdifficult to arouse but awakens to verbal stimuli or gentle shaking, follows simple commands but drifts off

again

2 Very sedatedVarouses to physical stimuli but does not communicate or follow commands, may move spontaneously

1 UnarousableVminimal or no response to noxious stimuli, does not communicate or follow commands

Guidelines for SAS assessment

1. Agitated patients are scored by their most severe degree of agitation as described

2. If patient is awake or awakens easily to voice (Bawaken[ means responds with voice or head shaking to a question or follows commands), that is an

SAS 4 (same as calm and appropriateVmight even be napping)

3. If more stimuli such as shaking is required but patient eventually does awaken, that is an SAS 3

4. If patient arouses to stronger physical stimuli (may be noxious) but never awakens to the point of responding yes/no or following commands, that is an

SAS 2

5. Little or no response to noxious physical stimuli represents an SAS 1. This helps separate sedated patients from those you can eventually wake up

(SAS 3), those you cannot awaken but can arouse (SAS 2), and those you cannot arouse (SAS 1)

Abbreviation: SAS, Sedation-Agitation Scale.




potent amnesic effect that combines with its satisfactorysedative effect.

The adverse effect of benzodiazepines, with theircumulative ability, will cause respiratory and cardiacdepression, hypotension, physical dependence, and some-times a paradoxical agitation.14 Prolonged sedation andunpredictable awakening from accumulation of the drugor their active metabolites make them difficult to adjustdosing, thus causing a prolonged recovery.15 Their am-nesic effect may reduce communication, leading to lesscooperation during weaning from mechanical ventilation.

In the elderly, especially those with comorbidities, theuse of benzodiazepines adds more challenges to healthcarepractitioners. Effects such as inadequate clinical assess-ment, excessive prescribing, and altered pharmacokineticsand pharmacodynamics occur with advancing age. Thelikelihood to potential side effects increases as a result ofchanges in distribution and elimination of medications.Benzodiazepines with their long half-lives can accumulatein the body.16 As we age, our CNS receptors change,becoming more sensitive with increased short-term mem-ory losses and unsteadiness. These are due to normalcharacteristics of aging such as dementia, hypoalbumine-mia, or chronic renal failure.17 The risk of falls increaseswith the elderly’s increased psychomotor impairments.Obese patients may require higher doses, but clearanceremains relatively the same.

That the primary hesitate issue for treating anxietyand agitation with benzodiazepams is the duration of se-dation is not precise enough. There are many clinical ca-veats in the typical ICU patient. These include inadequateblood flow and metabolic rates, low cardiac outputs orlittle cardiac reserve, and at times respiratory depressionwhen benzodiazepams are given with pain medications.

We know that agitation and anxiety can benarrowed when pain is treated with opioids. This classof drugs has some advantages. Common ones, such asmorphine and fentanyl, are easily titratable to effectwith rapid onsets of action. They are dose dependentwithin their class for sedation and analgesia.

Treating agitation solely with opioids is not recom-mended. Acute and chronic tolerances can occur. Theadverse effect when increasing administration can causeventilatory depression, hypotension, nausea, and vomit-ing.18 Again, when administered with benzodiazepines,it becomes difficult to wean patients from mechanicalventilation.

Some opioids cause vasodilation as a result ofhistamine release.19 These opiates cause histamine releasefrom mast cells, resulting in hypotension, urticaria,tachycardia, and pruritus.19 Morphine, codeine, andmeperidine are commonly used opioids that tend toexecute this with the effect being dose dependent.19

Toxicity doses of meperidine can cause dysphoriaand agitation. Although life-threatening opioid allergiesare rare, caution must be taken with any patient whohas shown a past sensitivity to an opioid.18

Fentanyl, another common analgesic, has beenfound to have a low histamine release.19 Unfortunately,fentanyl can potentially cause bradycardia.15 Fentanylinhibits synaptic activity to cardiac vagal neurons. Thedirect mechanism is not fully understood, but it isbelieved that one mechanism is the depression ofheart rate resulting from the drug inhibiting thefrequency and amplitude of GABA neurotransmis-sions.20 These transmissions come from the nucleusambiguus, the site of heart rate and cardiac functionorigin.20 Griffioen et al20 reported that this inhibitionwas mediated at both presynaptic and postsynapticsites. Their studies resulted in the demonstration thatfentanyl acts on 6-opioid receptors on cardiac vagalneurons and neurons preceding them to reduceGABA neurotransmission and increase parasympa-thetic activity.

TABLE 3 Adverse Side Effects

Unnecessary Side Effects Propofol Benzodiazepams Opioids Dexmedetomidine

Respiratory depression Yes Yes Yes No

Prolonged vent weaning Yes Yes Yes No

Constipation Yes No

Significant hypotension Yes Yes No

Lack of orientation Yes Yes Yes No

Lack of cooperation Yes Yes Yes No

Cumulative effects Yes Yes No

There are many clinical caveats in thetypical ICU patient.

May/June 2009 105



Opioids are fine for pain relief, but not solely foranxiety. Euphoria, defined as a feeling of happiness orwell-being sometimes exaggerated in pathological statesas mania, can be achieved with opioids. Reality is thendiminished from the critically ill patient.

Sedating patients with an increase in intracranialpressures or convulsions requires barbiturates.21 Thesepowerful drugs are similar to benzodiazepines. Barbitu-rates generate myocardial depression and vasodilation,resulting in tachycardia and hypotension by inhibitingcalcium uptake.22

Sedation goals for the ICU patient include control-ling anxiety for procedures and/or events.11 An impor-tant goal also is blunting the adverse autonomic andhemodynamic responses from the above medicationswhile facilitating mechanical ventilation. This bluntinglimits self-extubations and reduces oxygen consump-tion. This results in the enhancement of nursing care ofthe ICU patient as a result of a more comfortablepatient. The ideal sedative allows patients to sustainspontaneous ventilation, protect their airway, andremain cooperative and easily arousable.

Dexmedetomidine (Precedex), an !2-adrenergicreceptor agonist inhibits norepinephrine and epineph-rine centrally and peripherally.23 No other agent alonein the current therapeutic arsenal for pain, sedation,and analgesia can provide relief for all. It has a rapidonset (5 minutes) resulting in both sedation andanalgesia with no respiratory depression.9 It is oftencompared with clonidine, a one-eighth times less sedat-ing !2 agonist with similar properties.24 Potency for its!2 effect is 1,620 times more than dexmedetomidine’s!1.25

Physiological effects of dexmedetomidine includehypotension and bradycardia, reduction of plasmacatecholamine levels, and sedation, thereby reducinganalgesic and anesthetic requirements.26 Dexmedeto-midine, although used alone, can provide more ad-equate sedation and pain relief and less anxiety withlimited respiratory depression. The drug’s predictableeffects of bradycardia and hypotension increase itsmanageability.

The drug facilitates patient compliance and compre-hension with easy arousability. Allowing communica-tion with the nurse and other healthcare providers,while remaining sedated, enables a more comfortablestay for the patient. It is specifically indicated forintubated and mechanically ventilated patients in theICU and does not have to be discontinued beforeextubation. In clinical trials, dexmedetomidine hasshown significant efficacy for sedation in postsurgicalpatients as well as those who are agitated and overlyanxious uncooperative patients.23,25,27

DEXMEDETOMIDINE AND AGITATION

A Brief Review of !1 and !2, "1 and "2Effects of the sympathetic nervous system (SNS),whether from inflammatory responses or drugs, aredifferentiated into the ! and " receptors in the SNS. Theactivation of their receptors produces either excitatoryeffects in some tissues or inhibitory effects in others (seeTable 4).28 When the SNS is stimulated, we experiencean increase in heart rate and vasoconstriction with a.resulting elevated peripheral vascular resistance. There-fore, when these receptors are blocked, or the !2receptors stimulated, the opposite effect takes place.For this paper, the !2-adrenoreceptors are discussed,with dexmedetomidine being its agonist or stimulator.

Sympatholytic drugs block the sympathetic adrener-gic system on 3 levels: centrally, peripherally, andpostganglionically.7 They are primarily adrenergicantagonists, inhibitors of adrenergic receptors, or pre-synaptic adrenergic agonists inhibiting further impulsetransmissions to the sympathetic receptors. The cen-trally acting drugs block sympathetic outflow within thebrain. These medications block the activity of thesympathetic system by binding to and activating thepresynaptic !2-adrenoceptors, resulting in a decrease innorepinephrine release, leading to a decreased heartrate and contractility as well as vasodilation andhypotension.26

!-Receptors are found presynaptically, postsynapti-cally, and extrasynaptically. Presynaptic receptors, !2’s,regulate the amount of norepinephrine and adenosinetriphosphate through a negative feedback mechanism.29

Specifically, these !2 receptors are found in the periph-eral nervous system and CNS, platelets, and manyorgans including the kidneys, liver, pancreas, and eyes.The physiological responses mediated by these receptorstherefore vary with location.

From an anesthesiologic point, the !2 receptorsactivate guanine-nucleotide regulatory binding proteins

TABLE 4 ! and " Receptors

!1 Arteriolar constriction in skin, mucous membranes, and viscera,

causing an increase in peripheral resistance, dilated pupils,

and contracted bladder

!2 Reduced sympathetic outflow resulting in peripheral vasodilation

"1 Elevated heart rates (chronoscopic), increased force of cardiac

contraction (inotropic), and speed of conduction (dromotropic)

"2 Bronchodilation, dilated arterioles in skeletal muscles resulting in

decreased peripheral resistance, increased glycogenolysis and

gluconeogenesis in the liver and bladder, relaxation resulting in

decreased urine output




(G proteins).29 These activated proteins induce intra-cellular signaling pathways through a second messengersystem, which modulates ion-channel activity in thenerve terminal. The activated second messenger systeminhibits adenylate cyclase, an enzyme that decreases theformation of 3,5-cyclic adenosine monophosphate.29

The modulation of the ion-channel activity leads tohyperpolarization of the cell membrane and an efflux ofpotassium, resulting in a suppression of neuronal firing.Calcium conductance into cells is reduced from the!-adrenergic agonist by direct regulation of calciumentry through N-type voltage-gated calcium channels,independent of 3¶,5¶-cyclic adenosine monophosphateand protein phosphorylation.30 Therefore, this calciumsuppression affects analgesia by inhibiting the secretionof neurotransmitters.30

Activating the !2 receptors in the CNS inhibitsneuronal firing and causes hypotension, bradycardia,sedation, and analgesia. Other areas when stimulatedresult in decreased salivation and decreased bowelmotility, contraction of vascular and smooth muscle,inhibition of renin release with an increased glomerularfiltration, increased sodium and water retention in thekidneys, decreased intraocular pressure, and decreasedinsulin secretion.31

PHARMACOLOGY OF DEXMEDETOMIDINEDexmedetomidine is a specific and relatively selective!2-adrenoceptor agonist.24 The drug inhibits the releaseof norepinephrine at the presynaptic !2 receptors, whichin turn terminates the beginning of pain signals whilepostsynaptically activating the !2 receptors in the CNSand inhibiting the SNS’s elevation of blood pressure andheart rate. The net result of both these pathwaysproduces sedation, anxiolysis, and analgesia.

The suppressed neuronal firing effect produced bythe hyperpolarization with the G proteinYgated potas-sium channels and the reduced calcium entry inhibitingthe neurotransmitters being released represent 2 specificways of effecting analgesia.22 One stops the nerve cellfrom ever firing, and the other cannot send its signal toanother cell.

The sedative effect of dexmedetomidine comes fromthe largely dense postsynaptic !2 receptors found in thelocus caeruleus part of the brain (see Figure 1).32 This isconsidered the hypnotic or wakefulness modulator areain the brain. The locus caeruleus site is also the originfor nociceptive neurotransmission, where !2-adrenergicand opioidergic systems have common effector mecha-nisms (see Figures 2 and 3). Here, the dexmedetomidinemechanism of action inhibits the G protein that wouldhave increased conduction through potassium channels,thus resulting in sedation.30 Being easily arousable while

effectively sedated becomes another unique feature ofthe drug. This is not found with the use of other sedatives.33

All of the effects of producing analgesia, sedation,and anxiolysis make dexmedetomidine unique byproducing less side effects than from using multipleagents.34 Even while intubated, patients are calm,comfortable, and cooperative.

AdministrationThe recommended maintenance dose ranges from 0.2 to0.7 2g/kg.35 For conscious intubations, 0.5 2g/kg perhour is typically used.25 The initial loading dose, ifrequired, is 1 2g/kg over 10 minutes.35 Normal responseis within 6 minutes following IV administration. An IVinfusion pump should be used to control the dosageto the desired level of clinical sedation. There is nodifference in the pharmacokinetics of dexmedetomidinein young versus elderly and female versus males.36

Dexmedetomidine is compatible with lactatedRinger’s solution, D5%W, mannitol, etomidate, vecuro-nium, succinylcholine, glycopyrrolate, phenylephrine,atropine, midazolam, morphine, and fentanyl, amongothers.36

Dexmedetomidine infusions should not be contin-ued after 24 hours because its safety and effectivenesshave not been evaluated past this time period. Like long-term use of clonidine, dexmedetomidine shares a com-parable withdrawal syndrome. Adverse effects includehypotension, hypertension, nausea, bradycardia, atrialfibrillation, and hypoxia.36 Overdosage may cause first-or second-degree heart blocks. These effects are seenduring or briefly after loading the drug.36

Figure 1. Region of dense "2 receptors.32

May/June 2009 107



DistributionDexmedetomidine has a distribution half-life of approx-imately 6 minutes.35 It has a 93.7% average proteinbinding with no renal impairment effect.37 Patients withhepatic impairment may experience changes in proteinbinding, resulting in lowered clearance of the drug.36

There is no significant change in protein binding when inthe presence of other typical ICU medications such as di-goxin, lidocaine, warfarin, phenytoin, and propranolol.36

EliminationThe drug is excreted in the urine (95%) and feces (4%) afterextensive biotransformation by the liver.29 Eliminationhalf-life for dexmedetomidine is approximately 2 hours.36

Adverse Effects of DexmedetomidineBradycardia, along with various atrioventricular blocksand reduction of sympathoadrenergic hypertension, isthe most prominent adverse effect associated withdexmedetomidine.36 Cardiovascular events are predict-able because of the known effects. These effects maycause severe problems during ventilator weaning andduring transition to the wake state.

THE RESPONSIBILITY OF THE ACUTE CARENURSE PRACTITIONER AND CRITICAL CARENURSEFirst, the drug dexmedetomidine should be administeredonly by clinicians skilled in the management of the ICUpatient. These patients must be continuously monitored.Transient hypertension has been seen during the loadingdose with its peripheral vasoconstrictive effects.31 Gener-ally, treatment is not required, but reducing the loadingdose rate can be advantageous. Caution should beexercised in patients with any history of advanced heartblocks when infusing dexmedetomidine. Clinicians shouldbe prepared to intervene if hypotension or bradycardiaoccurs with the infusion. Treatment should includereducing or stopping the rate of infusion while administer-ing fluids or vasopressors. Pretreating with glycopyrrolate,a potent antimuscarinic, is a safe management tool inpreventing a potential adverse bradycardia. Sometimes,having available atropine or pacing at the bedside isrequired for unfavorable bradycardia.

Although compatibility has not been established,nothing should be administered with blood products.37

The drug must be diluted in 0.9% sodium chloride beforeadministration. Clearance can be slower with hepatic im-pairment. Therefore, it may be necessary to reduce the dosein patients with liver disease. If dexmedetomidine is ad-ministered continually thenabruptly discontinued,withdrawal

Figure 2. Responses of "2-adrenergic receptors.31

Figure 3. Responses mediated by !2-adrenergic receptors.29

Cardiovascular events are predictablebecause of the known effects.




symptoms, which include nervousness, agitation, rapidhypertension, and headaches, can occur.35

CONCLUSIONOversedation can cause respiratory depression, psycho-logical distress, metabolic abnormalities, a depressedimmune system, and a prolonged difficult weaning frommechanical ventilation. Certain physiological processesare masked or overlooked. On the other end, under-sedation will cause its own share of problems fromdisorientation, ventilator intolerances, and hemody-namic instability such as hypertension and tachycardia,thus increased oxygen consumption and demand.

Dexmedetomidine will enable intubated and venti-lated patients to be more arousable and responsivewhile reducing analgesic and anesthetic use. There is norespiratory depression, hemodynamic stability is main-tained, and oxygen demand is minimized.37

The benefits of dexmedetomidine, being a selective andspecific !-adrenergic receptor agonist, are clinically effectivefor sedation in the ICU. Dexmedetomidine represents a sig-nificant advance in managing and supporting ICU patients.

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ABOUT THE AUTHOR

Jeanne Boyer, RN, MSN, CCRN, ACNP, is an Acute Care Nurse

Practitioner for the Department of Anesthesia at Washington Hospital

Center, Washington, District of Columbia. She is a recent acute care nurse

practitioner graduate of the University of Maryland in Baltimore, Maryland.

Address correspondence and reprint requests to: Jeanne Boyer, RN,

MSN, CCRN, ACNP, 301 Queen Anne Rd, Stevensville, MD 21666

([email protected]).

May/June 2009 109



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Treating Agitation With Dexmedetomidine in the ICU