Diagnosing And Treating Delirium In The ICU - Rochester, NY
9/10/2013ObjectivesDelirium in theIntensive Care UnitChristine M. Groth, Pharm.D., BCPSCritical Care Clinical Pharmacy SpecialistCritical Care SymposiumSeptember 23th, 2013 Describe delirium, its prevalence, pathophysiology,and risk factors Describe the impact delirium has on patient outcomes Demonstrate how to use validated tools to monitorfor delirium Understand how to treat delirium bothpharmacologically and non-pharmacologically Describe the risks associated with antipsychotictherapyWhat is Delirium?Types of DeliriumComes from the Latin word delirare, to “derail”, “to go off the plowed usInattentionDisorganizedThinkingORAltered Level ofConsciousnessPeterson JF, et al. J AM Geriatr Soc 2006.Pandharipande, et al. Curr opin Crit Care 2005; 11:360-68.Prevalence Risk Factors for Delirium20-50% of non-intubated ICU patients60-80% of ICU patients receiving mechanical ventilationOften present on admissionMore common in patients 65 years of ageRemains unrecognized in 66-84% of patients Attributed to other disease statesTreated as an expected occurrenceNot routinely assessed in most ICUsOften missed due to fluctuating nature and variablepresentationPatient Factors Age Comorbidities HTN* Cognitive Impairment Dementia* Alcoholism* Genetics Apo lipoprotein E4phenotypeAcute Illness*Environment Mechanical ventilation Hypoxia Metabolicdisturbances/Electrolyteimbalance Sepsis/Acute infections Withdrawal syndromes Seizures Head trauma/Intracraniallesions Coma** Medications Sleep deficits Restraintuse/immobilization*HTN, dementia, alcoholism, and a high severity of acute Illness are positively and significantly associated with delirium** Coma is an independent risk factor for delirium in ICU patientsPun, et al. Chest 2007; 132:624-36.Hughes, et.al. Curr Opin Crit Care 2012, 18:518-26.Barr, et al. Crit Care Med 2013, 41(1):263-306.1
9/10/2013Pathophysiology Global brain dysfunction Patients with delirium have been found to have: Alterations in cerebral blood flow and metabolism Brain atrophy, lesions, ventricular enlargement Multifactorial Inflammation and cytokine release Hypoperfusion Imbalance in the synthesis, release, and inactivation ofneurotransmittersProlonged Length of Stay-Delirious patients spentmedian of 10 days longerin the hospital-20% increased risk ofstaying in the hospital foreach day spent in deliriumHR 1.2 GABA, Dopamine, Acetylcholine, SerotoninPandharipande, et al. Curr opin Crit Care 2005; 11:360-68.Increased MortalityEly, EW, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004Increased Health Care Costs-3-fold increased riskof 6-month mortality-10% increased risk ofdeath for each day spentin delirium HR 1.1-40% relative increasein ICU and total hospitalCostsEly, EW, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004Delirium Contributes to Long-termCognitive Impairment Delirious ICU patients were found to be nine times morelikely to have cognitive impairment at discharge than nondelirious patients (Ely, et at JAMA 2004) Delirium may lead to or accelerate development ofdementia Delirium tends to persist in patients discharged from thehospital and ICU (Levkoff, et al Arch Int Med 1992)Milbrandt EB, et al. Costs associated with delirium in mechanically ventilated patients. Crit Care Med 2004.Consequences Associated withDelirium Self-extubation 3-fold higher re-intubation rate Increased distress/anxiety for patients, families,caregivers Increased nosocomial Pneumonia Only about 4% of patients have full resolution of symptomsbefore discharge from the hospital 40% of those patients had a full recovery 6 months laterPun, et al. Chest 2007; 132:624-36.2
9/10/2013Monitoring Delirium in the ICU Recommended by the Society of Critical CareMedicine in all ICU patients ( 1B) Validated monitoring tools Confusion Assessment Method for the ICU (CAM-ICU) Intensive Care Delirium Screening Checklist (ICU-DSC)CAM-ICU Adapted from the original Confusion Assessment Methodfor use in ICU patients It has a sensitivity of 76-80% and specificity of 96% Four feature assessment1) Acute onset of mental status changes or a fluctuating course2) Inattention3) Disorganized thinking4) Altered level of consciousness Delirium is present when features 1 and 2 and either 3 or 4are positiveEly, EW. Et al. JAMA 2001;286(21):2703-10.Bergeron, N. et al. Intensive Care Med 2001; 27:859-864.Ely, EW. et al. JAMA 2001;286(21):2703-10.Brummel, et al. CCM 2013;41:2196-2208.CAM-ICUICU-DSC The Intensive Care Delirium Screening Checklist(ICDSC) is a validated screening tool for delirium inthe ICU It has a sensitivity of 74-80% and a specificity of 75-82% It is based on DSM-IV criteria and features of delirium It is an 8 point scale that is to be completed based ondata from each entire shift or from the previous 24hours A score 4 indicates deliriumBergeron, N. et al. Intensive Care Med 2001; 27:859-864.Brummel, et al. CCM 2013;41:2196-2208.ICU-DSCICU-DSC Inattention Difficulty in following a conversation or instructions. Easily distracted by external stimuli.Difficulty in shifting focuses Disorientation Any obvious mistake in time, place, or person Hallucination, delusion, psychosis The unequivocal clinical manifestation of hallucination or of behavior due to hallucination ordelusion such as grabbing at a non-existent object. Psychomotor agitation or retardation Hyperactivity requiring the use of additional sedative drugs or restraints in order to controlpotential dangerousness such as pulling out lines or hypoactivity or psychomotor slowing Inappropriate speech or mood Disorganized or incoherent speech. Inappropriate display of emotion related to events orsituation Sleep/wake cycle disturbance Sleeping less than 4 hours or waking frequently at night or sleeping most of the day Symptom fluctuation Fluctuation of symptoms over 24 hours or from shift to shift3
9/10/2013Case Study #1 GG is a 65 yof admitted with acute respiratory failure.She lives on her own, is active in church, and stilldrives a car. You walk into the room and she looks atyou immediately. She appears anxious as she is beingventilated with Bipap. Her arms are restrained andshe is pulling at them to get her Bipap mask off.Case Study #1 CAM-ICU Scored 5 on the letters of Feature 2 Answered 2 questions correctly and follows thecommands of Feature 4 Does GG have delirium? Lowest RASS in the previous 24 hours -2 (SAS 3) Highest RASS in the previous 24 hours 2 (SAS 6) Current RASS is?Case Study #2 KM is a 80 yom successfully weaned from theventilator and extubated post abdominal surgery. Heis alert and calm and all sedation has been stoppedthis am. Last evening he had periods of agitation witha documented RASS of -1 to 3 (SAS 3-7). He lives withfamily due to physical limitations but is cognitivelyintact. What is the current RASS?Case Study #2 CAM-ICU Answers all questions correctlyAble to identify the number of fingers you hold upFollows commandsSqueezes correctly on all letters Does KM have delirium?Case Study #3 JS is a 65 yof 2 days post-op for emergent abdominalsurgery. She is on the ventilator, eyes closed, doesnot open eyes to verbal stimuli, but does respond tophysical stimuli. She is receiving midazolam andfentanyl and has been off of paralytics for 24 hours.She has been RASS -5 to -2 (SAS 1-3) over the past 24hours. She does not follow any commands. Prior toadmission she had just retired from her teaching job. What is her current RASS?Case Study #3 ICU-DSC Only responds to deep intense physical stimulation Does not look at you or follow commands Has required frequent boluses of midazolam andfentanyl for agitation Does JS have delirium?4
9/10/2013Case Study #4Case Study #4 CC is a 78 yof admitted with a heart failureexacerbation that you have been caring for over thepast several days. She lives at home and cares for herhusband. She has been RASS -1 to 0 and ICU-DSCnegative for the past 48 hours. She is calm themorning and greets you by saying “How do you thinkI look?” You exchange pleasantries about how she isdoing today. What is her current RASS?Managing Delirium Treat underlying cause Risk factor modification Non-pharmacologic therapy ICU-DSC Calm and knows she is in the hospitalNo hallucinations or delusionsCan sleep when left aloneExpresses concern about her situation CAM-ICU Answers 2 questions correctly Follows commands Gets 6 letters and 5 pictures correct Does CC have delirium?Risk Factor ModificationOrientation Orient to person, place,and time Encouragecommunication Cognitively stimulate Provide visual and hearingaids Have familiar objects inthe room Attempt consistency innursing staff Early mobilization ( 1B) Promoting sleep ( 1C) Pharmacologic therapyEnvironment Maintain systolic bloodpressure 90 mmHg Maintain oxygensaturations 90% Treat underlyingmetabolic derangementsand infections Treat painBarr, et al. Crit Care Med 2013, 41(1):263-306.Barr, et al. Crit Care Med 2013, 41(1):263-306.Early Physical and Occupational Therapy inMechanically Ventilated, Critically Ill PatientsClinical Parameters Allow television onlyduring day Non-verbal music Sleep hygiene: Lights offat night, on during day Control excess noise andinterruptions at night Ambulate and mobilizeearly and often Remove catheters andrestraints Discontinue deliriogenicmedicationsMedication ManagementSchweickert, et al. Lancet 2009, 373:1874-82 Limit exposure to deliriogenic medications Early mobilizationprotocol reduced themedian number ofdays with ICUdelirium by half GABA-mimetics, anti-cholinergics, etc. Current Guidelinesrecommend topursue earlymobilization toreduce the incidenceand duration ofdelirium (1B)Pandharipande P, et al. Anesthesiol. 2006:104:21-26.Pandharipande P, et al. J Trauma 2008; 65:345
9/10/2013Medication Management Optimize the quantity and duration of sedatives andanalgesics to reduce the incidence of coma Use of protocol driven sedation Use of validated sedation scales (RASS, SAS)Treat pain first (analgo-sedation)Using intermittent doses vs. continuous sedationDaily interruption of sedation or targeting light levels ofsedationMedication Management Opioids Conflicting data Untreated pain associated with delirium Guidelines RECOMMEND IV opioids to treat nonneuropathic pain ( 1C) Propofol No significant relationship has been found GABA-mimetic Guidelines SUGGEST using over benzodiazepines forcontinuous sedation in non-delirious patients( 2B)Barr, et al. Crit Care Med 2013, 41(1):263-306.Barr, et al. Crit Care Med 2013, 41(1):263-306.Medication ManagementUse of Dexmedetomidine as a Sedative and AnalgesicAgent in Critically Ill Adult Patients: A Meta-analysisTan, et al. Int Care Med 2010, 36:926-39 Dexmedetomidine Alpha2-agonist with sedative and analgesic propertiesMay reduce the prevalence and increase delirium-free daysMay reduce time to extubationGuidelines SUGGEST using over benzodiazepines forcontinuous sedation in delirious and non-delirious patients( 2B) Does not provide deep sedation Expensive 400-1000/day Has not been compared to analgesia first sedationEffect of Dexmedetomidine on Risk of DeliriumPharmacologic Therapy Antipsychotics should not be used to prevent delirium inICU patients (-2C) There is no published evidence that haloperidol reducesthe duration of delirium in ICU patients (no evidence) Atypical antipsychotics may reduce the duration ofdelirium in ICU patients, but this needs to be validated insufficiently powered studies (C) Antipsychotics are not recommended in patients at risk fortorsades de pointes (-2C)Haloperidol Limited to case reports and anecdotal evidenceButyrophenone antipsychotic agentCompetitively blocks central dopaminergic receptorsOnset IV: 5-30 minutesLong half-life (18-54 hours)Loading regimen Double the dose every 15-20 minutes Give 100% of the total dose divided q6h Taper the dose over several days Baseline and daily QTc recommended (Hold if 500)Barr, et al. Crit Care Med 2013, 41(1):263-306.6
9/10/2013Effect of Intravenous Haloperidol on the Duration ofDelirium and Coma in Critically Ill Patients (HOPE-ICU)Page, et al. Lancet Resp Med 2013; 1:515-23 Randomized, double-blind, placebo-controlled trialn 142Haloperidol 2.5 mg IV q8h vs. NS placeboAll mechanical ventilated patients whether they weredelirious or not Randomized within 72 hours Treated for 14 days unless discharged from the ICU orhad two consecutive CAM-ICU negative screeningsAtypical Anti-PsychoticsEffect of Intravenous Haloperidol on the Duration ofDelirium and Coma in Critically Ill Patients (HOPE-ICU)Page, et al. Lancet Resp Med 2013; 1:515-23Primary Outcome: Median Deliriumand Coma-Free Days Haldol 5 (0-10) Placebo 6 (0-11)RR -0.48 (-2.08 to 1.21) p 0.53No difference in the proportion ofpatients with resolution over time(Figure)Trend towards reduced need forsedatives with haloperidolEfficacy and Safety of Quetiapine in Critically Ill Patientswith Delirium:A Prospective, multicenter, randomized, double-blind, placebo-controlled pilot studyCritical Care Medicine 2010 38(2):419-27 N 36 ICU-DSC positive patients, with a prn order forHaloperidol were randomized pineAripiprazole Quetiapine 50mg Q12H or matching placebo Titrated daily by 50mg Q12H to a maximum of 200mgQ12H if at least one dose of Haloperidol receivedEfficacy and Safety of Quetiapine in Critically Ill Patientswith Delirium:A Prospective, multicenter, randomized, double-blind, placebo-controlled pilot studyCritical Care Medicine 2010 38(2):419-27Efficacy and Safety of Quetiapine in Critically Ill Patientswith Delirium:A Prospective, multicenter, randomized, double-blind, placebo-controlled pilot studyCritical Care Medicine 2010 38(2):419-27 Time to First Resolutionof Delirium Quetiapine: 1 (0.5-3 )days Placebo: 4.5 (2-7) days7
9/10/2013Efficacy and Safety of Quetiapine in Critically Ill Patientswith Delirium:A Prospective, multicenter, randomized, double-blind, placebo-controlled pilot studySafety of Antipsychotic TherapyCritical Care Medicine 2010 38(2):419-27 Extrapyramidal effects due to D2 blockade Safety Haloperidol Atypicals No difference between groups: Atypicals have higher 5-HT2:D2 blockade Greater with oral haloperidol vs. intravenous QTc prolongation Extrapyramidal symptoms Higher concentrations of the pyridium metabolite Orthostatic hypotension Side effects due to Quetiapine α1-adrenergic antagonism Haloperidol clozapine quetiapine risperidone olanzapine 5 episodes of somnolence 1 episode of hypotension Antihistamine Clozapine and quetiapine are most sedating Anticholinergic Olanzapine quetiapine risperidone, ziprasidone,haloperidolRea, et al. Pharmacotherapy 2007; 27(4):588-94.Safety of Antipsychotic TherapySafety of Antipsychotic Therapy Medication Reconciliation/Safe discharge QTc prolongation Dose related Cardiac disease appears to predispose Reported most with haloperidol and ziprasidone Neuroleptic Malignant Syndrome Discontinue or taper once delirium resolves Public Health Advisory: Deaths with Antipsychoticsin Elderly Patients with Behavioral Disturbances JAMA 2005 meta-analysis All agents 1%15 randomized placebo-controlled trials3353 patients received study drug1757 patients received placeboOR 1.54 (p 0.02)Rea, et al. Pharmacotherapy 2007; 27(4):588-94.When Delirium is Present .THINK Toxic situations Hypoxia/hypercarbia Infection, inflammation,immobility Non-pharmacologic therapy K or other electrolyteabnormalitiesDR.DRE Diseases Drug Removal EnvironmentTips for Implementing DeliriumScreening in the ICU Multi-disciplinary “Delirium Champions” ICU leadership and nurse buy-in Use a validated screening tool CAM-ICU or ICU-DSC Identify and address barriers Perceived difficulty in using tools and assessingintubated patients Time constraintsBrummel, et al. CCM 2013;41:2196-2208.ICUdelirium.orgBrummel, et al. CCM 2013;41:2196-2208.8
9/10/2013Tips for Implementing DeliriumScreening in the ICUURMC ICU Delirium GuidelineIs the Patient Delirious (ICU-DSC positive (Score 4))?(See Delirium Assessment) Use multifaceted approach to train clinicians Reassess for delirium everyshiftTreat pain and anxietyDidactic instruction, videos, online resourcesCase studiesOne-on-one teachingCompliance metricsFollow-up training for feedback and reinforcementSAS of 6 to 7SAS of 4 to 5Is the patient inpain?YESGive analgesic(See painguideline)NOSAS of 2 to 3Assure adequate paincontrolReassess targetsedation goal(See pain guideline)(See sedation guidelines)Consider antipsychotic 3Give adequate sedativefor safety then minimizeand/orConsider treatment for*Acute Delirium*3Adapted from ICUdelirium.orgBrummel, et al. CCM 2013;41:2196-2208.URMC ICU Delirium GuidelineConclusions3. ANTIPSYCHOTIC THERAPYConsider stopping or substituting for:-BenzodiazepinesYESConsider differential diagnosis to r/oother causes for change in mental statuse.g. Sepsis, CHF, metabolicdisturbancesRemove deliriogenic drugs 1Non-pharmacological therapy2 Incorporate into interdisciplinary rounds anddocumentation systems Small changes at a time or plan-do-study-act cycles Develop a delirium management protocol/guideline1. DELIRIOGENIC MEDICATIONSNOWhile tapering or discontinuing sedatives, consider:-Anticholinergics-Haloperidol 5 mg IV/PO q6h, increase dose by 5 mg to max of-Corticosteroids-Promethazine20 mg q6h (consider lower starting dose in elderly e 50-400 mg/day PO divided twice daily-H2 Antagonists2. NON-PHARMACOLOGIC THERAPY-Olanzapine 2.5-20 mg/day PO divided once or twice daily Haloperidol 1-10mg IV q2h prn can be used for breakthroughsymptomsOrientation Provide visual and hearing aids Encourage communication and reorient patients Have familiar objects in the room Attempt consistency in nursing staff Allow television during day with daily news Non-verbal music*Acute Delirium* Haloperidol 3-5 mg IV x1 for acute delirium(ICU-DSC positive and SAS of 6 to 7) Double previous Haloperidol dose every 20 minutes until patientcontrolled or maximum dose of 40 mg is reached Haloperidol maintenance dose is 25% of total dose given tocontrol agitation every six hoursEnvironment Monitor QTc daily if on a scheduled antipsychotic regimen-Hold if QTc is 0.5 msec Sleep hygiene: Lights off at night, on during day Control excess noise at night Ambulate and mobilize early and often Discontinue antipsychotics if high fever, QTC prolongation, or druginduced rigidity occursClinical Parameters High prevalence of delirium in ICU patientsPathophysiology not completely understoodAssociated with worse outcomesCan persist and lead to long-term cognitive impairmentAll ICU patients should be screened for deliriumPrevention is keyNon-pharmacologic therapy should be treatment of choiceAntipsychotic therapy can be used for hyperactive deliriumChoice of agent and safety are uncertain Maintain systolic blood pressure 90 mmHg Maintain oxygen saturations 90% Treat underlying metabolic derangements and infections9
Delirium is present when features 1 and 2 and either 3 or 4 are positive CAM-ICU Ely, EW. et al. JAMA 2001;286(21):2703-10. Brummel, et al. CCM 2013;41:2196-2208. CAM-ICU The Intensive Care Delirium Screening Checklist . Diagnosing and Treating Delirium in the ICU .
Dementia and Delirium What we do know: 1. Delirium often does not fully resolve 2. After delirium dementia is more common 3. People with dementia get delirium more Theories 1. Delirium as a marker 2. Delirium as a trigger 3. Delirium as a cause 4. Treatment of Delirium as a cause 69% of patients with
If delirium is suspected, treat for delirium until confirmation by the medical team. 1.5.2 Ensure that the diagnosis of delirium is documented in the patient's clinical record. 1.5.3 Commence a delirium care plan 1.5.4 Note on the hourly care rounds any signs of delirium in order to document the fluctuations. 1.6 Treating delirium Initial .
delirium. If it has not been possible to establish whether a person has delirium, dementia or delirium superimposed on dementia, the referrer should treat for delirium first. For guidance on treating delirium, see NICE guidance Delirium: prevention, diagnosis and management 2010, updated 2019 (CG103)3. The referrer should also screen for other .
Diagnosing Delirium O Clinical diagnosis O Often missed by providers (Inouye et al., 2014) O Study by Han et al., (2009) found that 76% of delirium cases were missed by ER physicians and that increased the likelihood that this would also be missed by . Treating Delirium .
Management of delirium should include treating reversible causes where possible and desirable, according to the goals of care. Approximately 25 to 45 percent of episodes of delirium are . Under-diagnosing is often a problem in delirium (4-6,11,12). The decision to carry out investigations must be weighed against the value that will
3 Clinical transformation and education: Consultancy and training to educate staff so they can effectively implement delirium management improvements 2 Delirium management analysis: Assesses the delirium-related factors that need to be addressed to improve delirium management based on measured data 4 Interventions and improvements:
absence) of delirium. This data was then extracted into a large data set and cleaned. The risk factors were used to create a delirium prediction model which was incorporated into the EMR to run in real time. Results: The data set includes data from 13,819 unique patients and 153,212 independent delirium screens. Delirium incidence is 29.6%.
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