analgesia and sedation

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Analgesia and Sedation Analgesia and Sedation Pain is a more terrible lord of mankind than even death itself A lbert Schweitzer

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Analgesia and Sedation. Pain is a more terrible lord of mankind than even death itself A lbert Schweitzer. Analgesia and Sedation By Dr.M.H.Jarrahzadeh Intensivist. - PowerPoint PPT Presentation

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Page 1: Analgesia and Sedation

Analgesia and SedationAnalgesia and Sedation

Pain is a more terrible lord of mankind than even death itself

A lbert Schweitzer

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2

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Analgesia and SedationAnalgesia and Sedation

ByBy

Dr.M.H.JarrahzadehDr.M.H.Jarrahzadeh Intensivist Intensivist..

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Pain Pain is a more terrible is a more terrible lord of mankind than lord of mankind than even death itselfeven death itself..

AAlbert Schweitzerlbert Schweitzer

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****contrary to popular perceptioncontrary to popular perception , , our principalour principal

function in patient care is function in patient care is not tonot to save livessave lives

but to but to relieve pain and sufferingrelieve pain and suffering

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OpiophobiaOpiophobiaThe problem of inadequate pain control is

partly due to misconceptions about the

addictive potential of opioids, and about the

appropriate dose1 .Opioid use in hospitalized

patients does not cause drug addiction.

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22 . .The effective The effective dose of an dose of an opioidopioid should beshould be

determined by determined by patient responsepatient response

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Pain in the ICUPain in the ICUAlthough a majority of ICU patients receive parenteral analgesics

Routinely, 50%Of patients discharged from the ICU remember pain as their worst experience while in the

ICU .This emphasizes the need for effective pain control in the ICU.

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Monitoring PainMonitoring PainPain is a subjective sensation

that can be described in terms of intensity, duration,location ,quality (sharp, dull) .

pain intensity is the parameter most often monitored because it best reflects the degree of discomfort.

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The intensity of pain The intensity of pain can becan berecorded using a variety of scalesrecorded using a variety of scales,,

11(-(-ajective Rating Scaleajective Rating Scale ) )

22(-(-Numerical Ranking ScaleNumerical Ranking Scale))

33(-(-Visual Analog ScaleVisual Analog Scale))

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Opioid are most effective for relieving dull tonic pain, less

effective for intermittentsharp pain, and relatively ineffective

for neuropathic pain .

Although opioids cause mildsedation, they do not cause amnesi

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Opioid AnalgesiaOpioid Analgesiaeffects by stimulating discrete opioid receptors

in thecentral nervous system are called opioids.

Stimulation of opioid receptors produces avariety of effects, including analgesia,

sedation, euphoria, pupillary constriction,

respiratory depression, bradycardia, constipation, nausea, vomiting, urinary retention,and pruritis ,euphoria, stupor, com

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Intravenous Intravenous OpioidsOpioids

The opioids used most often in the ICU are

*Morphine*Fentanyl

*hydromorphone

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!!RememberRemember that the effective dose ofan opioid is determined by each patient's response, not by the numeric value of the

Dose.

Continued pain relief often requires continued drug administration

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FFentanyl versus Morphineentanyl versus Morphine

Morphine is the most frequently used opioid in ICUs .but fentanyl may be preferred 1-faster acting, 2- devoid of active metabolites, 3-less likely to decrease

blood pressure .

Opioids are metabolized1 -primarily in the liver, 2- the metabolites are excreted in the urine.

Morphine has several active metabolites several active metabolites that can accumulate in renal failure .

1-morphine-3-glucuronidemorphine-3-glucuronide can produce central nervous system excitation whith myoclonus and seizure 2-morphine-6-glucuronidemorphine-6-glucuronide( has

more analgesic effect than the parent drug

the maintenance dose the maintenance dose of morphine should be reduced by 50% inpatients with renal failure

FentanylFentanyl does not have active metabolites, and Dose not need adgustments in renal failur

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((PRNPRN) drug drug administration is a administration is a recipe for inadequate recipe for inadequate pain control and is pain control and is never recommendednever recommended

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!!CaveatCaveat..

Infusions of fentanyl Infusions of fentanyl lasting longer than lasting longer than 4 4 hours hours can produce prolonged drug effects can produce prolonged drug effects as a result of as a result of drug accumulation in fatty drug accumulation in fatty tissuetissue

This effect can be minimized by This effect can be minimized by titrating thetitrating thedose down to the lowest possible dose down to the lowest possible dose that relieves paindose that relieves pain

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Patient-Controlled AnalgesiaPatient-Controlled Analgesia

For patients who are awake and capable of drug self-administration. The PCA method uses anelectronic infusion pump that can be activated by the patient .

PCAPCA can be usedalone or in conjunction with a low-dose opioid infusion.

PCAPCA improved patient satisfaction, and fewerside effects than traditional intermittent opioid administration

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Adverse Effects of OpioidsAdverse Effects of OpioidsRespiratory DepressionRespiratory Depression

Opioids, dose-dependent decrease in both respiratory rateand tidal volume .but respiratory depression and hypoxemia are uncommon

When opioids causedifficulty in arousal, there is almost always an associated respiratory depression withHyper capnia

.Contraindication1-sleep apnea 2-chronic hypercapnia

Cardiovascular effectsCardiovascular effectsOpioid analgesia by decreases in blood pressure and heart rate the result of decreased sympathetic activity and increased parasympathetic

activity .Opioid-induced hypotension usuallyresponds to intravenous fluids or small bolus doses of vasopressors

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Intestinal MotilityIntestinal Motility

depress bowel motility, and this effect can be prominent in ICU patients .

Oral naloxone in a dose of 4 to 8 mg every 6 hours can antagonize opioid-induced bowel

hypomotility without antagonizing the systemic analgesic effect(

PruritisPruritis

10% of patients receiving intravenous opioids have pruritis,symptoms areusually not relieved by antihistamines, but they can be abolished by a low-dose

naloxone infusion )0.25–1 mg/kg/hr( without loss of analgesic effects

Nausea and VomitingNausea and VomitingOpioids can promote vomiting via stimulation of the chemoreceptor trigger zone in the lower brain stem

Antiemetic agents )ondansetron( and low doses of opioid antagonists can also produce

effective symptom relief

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MeperidineMeperidine )Demerol, Pethidine()Demerol, Pethidine(

Meperidine is metabolized in the liver to form normeperidine, and excreted by the kidneys )elimination half-life is

5–40 hours.Accumulation of normeperidine can produce central nervous system excitation with agitation, tremors, myoclonus, delirium, hallucinations, and tonic–clonic Seizure

Because of the risk for neurotoxicity in critically ill patients, meperidine is not advised forpain control in ICU patients. The traditional belief that meperidine is the preferred opioidfor pain relief in cholecystitis and pancreatitisthat meperidine and morphine are equivalent in their ability to promote spasm of thesphincter of Oddi and increased intrabiliary pressure

meperidine continues to be the preferred agent for control of shivering. In postoperative patients, low doses ofMeperidine 25 mg IV usually stop shivering due to hypothermia Meperidine within 5 minutes

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Nonopioid AnalgesiaKetorolacKetorolacKetorolac is a nonsteroidal antiinflammatory drug, )NSAID( introduced in 1990 as aparenteral analgesic for postoperative pain Because ketorolac does not causesedation or respiratory depression ,

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Analgesic EffectsAnalgesic Effects

Ketorolac is a nonspecific inhibitor of cyclooxygenase with strong analgesic activity and moderate antiinflammatory activity ., it is 350 times more potent

than aspirin .After intramuscular )IM( injection of ketorolac,

analgesia is evident at 1 hour, peaks at 2 hours, and lasts 5–6 hours .

The drug is partly metabolized in

the liver and excreted in the urine. For postoperative analgesia, 30 mg ketorolac IM is equivalent to 10 to 12 mg morphine IM .

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Dosing RegimenDosing Regimen

Ketorolac can be given orally, intravenouslyorally, intravenously, or by IMIM injection .

the initial dose is 30 mg IV or 60 mg IM, followed by 30 mg IM or IV every 6hours )maximum of 120 mg/day( for up to 5 days.

Because IMinjection of ketorolac can cause hematoma formation, IVIV bolus injection is preferred Ketorolac has also been given by continuous IV infusion )5 mg/hr(,

resulting in moreeffective analgesia than intermittent IV doses

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Adverse effectsketorolac inhibits platelet aggregation, and it should not be used inpatients with a high risk of bleeding

ketorolac high dose and use exceed 5days increased risk of gastrointestinal and operative site bleeding .

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Anxiety in the ICUAnxiety and related disorders )agitation and delirium( are evident in as many as 85% of patients in the ICU Anxiety is characterized by exaggerated feelings of fear,

nervousness, or apprehension that are sustained more by internal than external events.

Agitation is a combination of anxiety and increased motor activity .

Delirium is a specific syndrome of altered mental status that may or may not have anxiety.

Although delirium is often equated with agitation, there is a hypoactive form of delirium that is characterized by lethargy .

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SedationSedationSedation is the process of establishing a state of calmcalm .

The first steps to calm an anxious pation, Talkingalking to patients and making

adjustments in the ICU environmentICU environment.In the ICU, however, drugs are often needed to calm patients, and as many as 22different medications are used for this purpose. The agents most frequently used are

midazolam, propofol, lorazepam, and opioid midazolam, propofol, lorazepam, and opioid analgesicsanalgesics

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Monitoring SedationA number of scoring systems are available for this purpose,.Each system evaluates consciousness first bynoting spontaneous responsiveness to the observer, and subsequently )if necessary( bynoting responses to graded levels of external

stimulation )voice or touch()voice or touch( . .sedationScores are not intended for patients who are unconscious or receiving a neuromuscularblocking agent.

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The Ramsay scale The Ramsay scale was the first scoring system forevaluating sedation in mechanically ventilated patients .This scale is designed to monitor the level of consciousness more than the degree of agitation because it distinguishes four levels of sedation )score 3 to 6(, but only one level of agitation )score=1( ,

Ramsay scale is thechosen method of monitoring sedation in more than 75% of ICUs

Other sedation scales are included The sedation-analgesia scale )SAS(distinguishes three different levels of agitation and the Richmond Agitation

Sedation Scale )RASS( offers the advantage of following changes in the level of sedation on consecutive days

The goal of sedation in the ICU is a patient who is calm but easily arousable .

The use of a sedation scale will allow you to achieve and maintain this goal with the lowest possible dose of a sedative agent and with the lowest possible risk of harm to your

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Sedation with BenzodiazepinesSedation with Benzodiazepines

Benzodiazepines are popular sedatives in the ICU because they are generally safe to use, and the sedation is accompanied by amnesia. Of the 13 benzodiazepines available for clinical use, 3 can be given intravenously:

midazolam, lorazepam, and diazepammidazolam, lorazepam, and diazepam..

1 .All are lipid soluble lipid soluble to some degree, metabolized in the liverliver, and excreted

in the the urineurine.

2 .Therapeutic doses of benzodiazepines do not cause respiratory depression in healthy subjects, but this effect can occur in select ICU

patients )respiratory insufficiency(

3 .The dose of benzodiazepines needed to achieve adequate sedation is lower

in elderly patients ,and in patients with heart failure and hepatic insufficiency, due to a slowing of benzodiazepine metabolism

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4 .Even though the elimination half-life of diazepam is 20 to 50 hours versus 2 to 8

hours for midazolam,the clinical recovery time is the .same following a single intravenous dose of each drug

This discrepancy is explained by the relativelyrapid uptake of diazepam from plasma into fatty tissues. Avid uptake by fat is also observed with lorazepam.

5 .When an overdose of lorazepam or diazepam is

given, the clinical recovery time until the patient is fully awake may be prolonged as a result of drug accumulation

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Drug ComparisonsDrug ComparisonsMidazolam )Versed( is the benzodiazepine of choice for short-term sedation because ithas the** highest lipid solubility, **the fastest onset, **the shortest duration of action of all the intravenous benzodiazepines .

Because of its short duration of action, midazolam is commonly given by continuous infusion .

Infusions of midazolam lastingmore than a few hours can produce prolonged sedation after the drug infusion isstopped. This effects is the result of multiple factors, including )a( drug accumulation inthe central nervous system, )b( accumulation of an active metabolite

(hydroxy midazolam ,)especially in renal failure, )c( inhibition of cytochrome P450(involved in midazolam metabolism )by other medications . )d( hepatic

Insufficiency. To reduce the risk for over sedation, the infusion rate ofmidazolam should be determined using ideal body weight rather than total bodyWeight.

Lorazepam )Ativan( has the slowest onset of action of the intravenous benzodiazepines.

Because of its long duration of action, lorazepamis best suited for patients who require prolonged sedation )ventilator-dependentPatients)

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Diazepam )Valium(Diazepam )Valium(

is the least favored of the intravenous is the least favored of the intravenous benzodiazepines because ofbenzodiazepines because ofthe risk for the risk for over sedationover sedation with repeated drug with repeated drug administrationadministration..

Continuous infusions ofContinuous infusions ofdiazepam should be diazepam should be avoidedavoided because of the because of the risk for prolonged sedation caused byrisk for prolonged sedation caused byaccumulation of parent drug and its accumulation of parent drug and its active active hepatic metaboliteshepatic metabolites.

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Toxic EffectsToxic EffectsExcessive dosing of benzodiazepines can produce hypotension, respiratory depression,and excessive sedation .

Propylene Glycol ToxicityIntravenous preparations of lorazepam and diazepam contain the solvent propyleneglycol to enhance drug solubility in plasma .

This solvent can cause **local irritation to veins,

.A bolus of propylene glycol cancause hypotension and brady cardia,

prolonged administration of propylene glycolcan cause paradoxical agitation, metabolic acidosis, and a clinical syndromethat mimics severe sepsis

Withdrawal SyndromeAbrupt termination following prolonged benzodiazepine administration can produce awithdrawal syndrome consisting of anxiety, agitation, disorientation, hypertension,tachycardia, hallucinations, and seizures. cause of unexplained delirium in the first few days after ICU admission .

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Drug InteractionsDrug Interactions

Several drugs interfere with hepatic oxidative Several drugs interfere with hepatic oxidative metabolism of metabolism of diazepam and midazolamdiazepam and midazolam;;

These interactions do not apply to These interactions do not apply to lorazepamlorazepam, which is, which ismetabolized by metabolized by glucuronidationglucuronidation. .

Theophylline Theophylline antagonizes antagonizes benzodiazepinebenzodiazepinesedation sedation possibly by inhibiting adenosinepossibly by inhibiting adenosine , ,

and intravenous aminophylline and intravenous aminophylline )110 mg over 5)110 mg over 5minutes( minutes( has been reported to cause more rapid has been reported to cause more rapid awakening from benzodiazepineawakening from benzodiazepine

..sedation in post operative patientssedation in post operative patients

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PropofolPropofol

PropofolPropofol )Deprivan( is a rapidly acting )Deprivan( is a rapidly acting sedative agent that is used for induction andsedative agent that is used for induction andmaintenance of anesthesia and short-term maintenance of anesthesia and short-term sedationsedation. .

The use of this drug in theThe use of this drug in theICU should be limited by the risk for ICU should be limited by the risk for adverse reactionsadverse reactions)particularly hypotension()particularly hypotension(..

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Actions and UsesActions and UsesPropofol causes sedation and amnesia but has no analgesic activity , A singleintravenous bolus of propofol produces sedation within 1 minute,

and the drug effect lasts 5–8 minutes .. Due to its short

duration of action, propofol is given as a continuous infusion. After discontinuing apropofol infusion, awakening occurs within 10-15 minutes, even after prolonged administration.

Propofol can be used for short-term sedation when rapid awakening is desired, )during brief procedures( ,

propofol can be useful in neurologic injury because it reduces cerebral oxygen consumption and intracranial pressure .

Other conditions where propofol has been used include refractory status epilepticus and delirium tremens

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**Preparation and DosagePreparation and Dosage

Propofol is very lipid soluble, and the drug is suspended in a 10% lipid emulsion toenhance solubility in plasma. This lipid emulsion is almost identical to 10% Intralipid usedin parenteral nutrition formulas, and the nutritive content of the emulsion )0.1 mg fat/ml or

1.1 kcal/ml( should be counted as part of the daily nutrient intake .

*Propofol no dose adjustment is required forrenal failure or moderate hepatic insufficiency

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Adverse EffectsAdverse EffectsPropofol is well known for producing

**pain on injection, *respiratory depression,* pain on injection, *respiratory depression,* apnea, *Hypotensionapnea, *Hypotension .

Because of the risk of respiratory depression, infusions of the drug should be used only in patients on controlled ventilationcontrolled ventilation . .

*significant hypotension ismost likely to occur in patients who are elderlyelderly or have heart failureheart failure

Propofol should be avoided in patients with hemorrhagic hemorrhagic shockshock.

Anaphylactoid reactions to propofol are uncommon but can be severe

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The lipid emulsion in commercial propofol preparations can be a source of unwanted side effects .

Hypertriglyceridemia occurs in up to 10% of patients receiving propofol,especially after 3 days of

continuous infusion .Serum triglyceride levels should therefore be monitore during prolonged propofol infusions .

The lipid emulsion also promotes bacterial growthand improper sterile technique when giving propofol has resulted in an epidemic ofhyperthermic reactions and postsurgical wound

infections. To suppress microbial growth, commercial preparations of propofol contain either )disodium edetate )EDTA .AstraZeneca( or sodium metabisulfite

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Bradycardia—Acidosis )Propofol Bradycardia—Acidosis )Propofol InfusionSyndromeInfusionSyndrome(

is a rare and often lethalidiosyncratic reaction characterized by the abrupt onset of heart failure, bradycardia,lactic acidosis, hyperlipidemia, and rhabdomyolysis.

The underlying mechanism is not clear, but this syndrome is usually associated with prolonged andhigh-dose propofol infusions

(4–6 mg/kg/hr for longer than 24 to 48 hrs)

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HaloperidolHaloperidolHaloperidol )Haldol( is an appealing sedative for ICU patients because there is little or norisk of cardiorespiratory depression. Haloperidol is also effective in calming patients withdelirium )agitation or confusional anxiety( .

The intravenous route has yet to receiveapproval by the FDA, but intravenous haloperidol has been described in over 700Publications and is supported by the practice guidelines of the Society of CriticalCare Medicine.

ActionsActionsHaloperidol produces its sedative and antipsychotic effects by blocking dopamine receptors in the central nervous system.

Following an intravenous dose of haloperidol,sedation is evident in 10 to 20 minutes, and the effect lasts for hours. The prolongedduration of action makes haloperidol poorly suited for continuous infusion .

SedationSedationis not accompanied by respiratory depression, and hypotension is unusual

unless the patient is hypovolemic or receiving a ß-blocker.

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UsesUses.Due to its delayed onset of action, haloperidol is not indicated for immediate control of anxiety .

A benzodiazepine )lorazepam 1 mg( can be added to achieve more rapidSedation.

Haloperidol is often targeted for the patient with delirium. However,because of the lack of respiratory depression, the drug can be used to sedateventilator-dependent patients, and to facilitate weaning from mechanical ventilation.

DosageDosage.The dose recommendations for intravenous haloperidol are shown in Table 49.7Individual patients show a wide variation in serum druglevels after a given dose of haloperidol .Therefore, if there is no evidence for a

sedative response after 10 minutes, the dose should be doubled. If there is a partial

response at 10–20 minutes, a second dose can be given along with 1 mg lorazepamLack of response to a second dose of haloperidol should prompt a switch to another agent

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Adverse EffectsAdverse EffectsDopamine antagonism in the basal ganglia can cause extrapyramidal reactions; however,these are uncommon when haloperidol is given intravenously.

The incidence ofextrapyramidal reactions is further decreased when haloperidol is given in combination with a benzodiazepineHalperidolHalperidol should be avoided in patients with Parkinson's diseaseParkinson's disease..

The most feared adverse effects of haloperidol are the neuroleptic malignant syndrome

and torsades de pointes )polymorphic ventricular tachycardia( .

the neuroleptic malignant syndrome is a rare idiosyncratic reactionthat presents with hyperthermia, severe muscle rigidity,

and rhabdomyolysis ,

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Approach to the Agitated PatientApproach to the Agitated Patient

A common scenario in the A common scenario in the ICUICU is a nurse informing you that your is a nurse informing you that your patient has suddenly become agitated.. When youpatient has suddenly become agitated.. When youarrive at the bedside, your first priority is to exclude an immediate arrive at the bedside, your first priority is to exclude an immediate threat to life )review the patient's ABCs, Airway, Breathing, and threat to life )review the patient's ABCs, Airway, Breathing, and

Circulation(Circulation( . .

Then proceed by considering theThen proceed by considering thefollowing conditions in orderfollowing conditions in order: : pain, anxiety, and deliriumpain, anxiety, and delirium . .

For each condition, ask theFor each condition, ask thepatient if the condition is present and, if present, assess the patient if the condition is present and, if present, assess the

severity using an appropriate clinical scoring systemseverity using an appropriate clinical scoring system . .Then attempt to identify and correct the cause, and use theThen attempt to identify and correct the cause, and use theappropriate medication to alleviate symptoms. If the first condition appropriate medication to alleviate symptoms. If the first condition

)pain( )pain( is not present, proceed to the second condition, and so onis not present, proceed to the second condition, and so on

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