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Assessing and Managing Sedation in the Intensive Care and the Perioperative Settings. Assessing and Managing Sedation. SEDATION Curriculum Learning Objectives. Manage adult patients who need sedation and analgesia while receiving ventilator support according to current standards and guidelines
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Assessing and Managing Sedation in the Intensive Care and the Perioperative Settings
SEDATION Curriculum Learning Objectives • Manage adult patients who need sedation and analgesia while receiving ventilator support according to current standards and guidelines • Use validated scales for sedation, pain, agitation and delirium in the management of these critically ill patients • Assess recent clinical findings in sedation and analgesia management and incorporate them into the management of patients in the acute care, procedural, and surgical sedation settings
Predisposing and Causative Conditions Hospital Acquired Illness Invasive, Medical, & Nursing Interventions Acute Medical or Surgical Illness Mechanical Ventilation Medications Underlying Medical Conditions ICU Environmental Influences Anxiety Pain Delirium Agitation Management of predisposing & causative conditions Sedative, analgesic, antipsychotic, medications Interventions Agitation, vent dyssynchrony Pain, anxiety Calm Alert Free of pain and anxiety Lightly sedated Deeply sedated Dangerous agitation Unresponsive Spectrum of Distress/Comfort/Sedation Sessler CN, Varney K. Chest. 2008;133(2):552-565.
Need for Sedation and Analgesia Prevent pain and anxiety Decrease oxygen consumption Decrease the stress response Patient-ventilator synchrony Avoid adverse neurocognitive sequelae Depression, PTSD Rotondi AJ, et al. Crit Care Med. 2002;30:746-752. Weinert C. Curr Opin in Crit Care. 2005;11:376-380. Kress JP, et al. Am J Respir Crit Care Med. 1996;153:1012-1018.
Potential Drawbacks of Sedative and Analgesic Therapy Oversedation: Failure to initiate spontaneous breathing trials (SBT) leads to increased duration of mechanical ventilation (MV) Longer duration of ICU stay Impede assessment of neurologic function Increase risk for delirium Numerous agent-specific adverse events Kollef MH, et al. Chest. 1998;114:541-548. Pandharipande PP, et al. Anesthesiology. 2006;104:21-26.
American College of Critical Care Medicine Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult Guideline focus Prolonged sedation and analgesia Patients older than 12 years Patients during mechanical ventilation Assessment and treatment recommendations Analgesia Sedation Delirium Sleep Update expected in 2012 Jacobi J, et al. Crit Care Med. 2002;30:119-141.
FACES Pain Scale 0–10 Wong DL, et al. Wong’s Essentials of Pediatric Nursing. 6thed. St. Louis, MO: Mosby, Inc; 2001. p.1301.
Behavioral Pain Scale (BPS) 3-12 Payen JF, et al. Crit Care Med. 2001;29(12):2258-2263.
BPS ValidationSedated Mechanically Ventilated Patients Is BPS Sensitive to Pain? Is BPS Reproducible? Weighted = 0.74, P< 0.01 □ Not painful n = 104 ● Painful n = 134 ▲ Retested painful n = 31 Re-Exposed to Pain BPS Exposed to Pain * P < 0.05 vs rest period †P< 0.05 vs not painful Payen JF, et al. Crit Care Med. 2001;29:2258–2263.
Critical Care Pain Observation Tool 0-8 Gélinas C, et al. Am J Crit Care. 2006;15:420-427.
Critical Care Pain Observation Tool Sensitivity/Specificity DURING Painful Procedure Gélinas C, et al. Am J Crit Care. 2006;15:420-427.
Correlating Pain Assessment withAnalgesic Administration in the ICU Assessed Treated • Fewer patients assessed for pain, more treated with analgesics in ICUs without analgesia protocols compared with ICUs with protocols1 * Patients (%) * • Pain scoring used in 21% • of surveyed ICUs in 20062 Protocol No Protocol * P < 0.01 vs ICUs using a protocol 1. Payen JF, et al. Anesthesiol. 2007;106:687-695. 2. Martin J, et al. Crit Care. 2007;11:R124.
Assessing Pain Reduces Sedative/Hypnotic Use What proportion of MV ICU patients received sedative or hypnotic medication? Payen JF, et al. Anesthesiology. 2009;111;1308-1316.
Assessing Pain Improves Some Outcomes Payen JF, et al. Anesthesiology. 2009;111:1308-1316. Thromboembolic events, gastroduodenal hemorrhage, and CVC colonization were less than 10%, and not changed by pain assessment.
Sedation-Agitation Scale (SAS) Riker RR, et al. Crit Care Med. 1999;27:1325-1329. Brandl K, et al. Pharmacotherapy. 2001;21:431-436.
Richmond Agitation Sedation Scale (RASS) Verbal Stimulus Physical Stimulus Ely EW, et al. JAMA. 2003;289:2983-2991. Sessler CN, et al. Am J Respir Crit Care Med. 2002;166(10):1338-1344.
r2Kappa SAS Riker, 1999 0.83 0.92 Brandl, 2001 0.93 RASS Sessler, 2002 0.80 Ely, 2003 0.91 Ramsay Riker, 1999 0.88 Ely, 2003 0.94 Olson, 2007 0.28 MAAS Devlin, 1999 0.83 Hogg, 2001 0.81 MSAT Weinert, 2004 0.72-0.85 Sedation Scale Reliability
Correlating Sedation Assessment withSedative Administration in the ICU • 1381 ICU patients included in an observational study of sedation and analgesia practices1 • Fewer patients assessed, more treated with sedatives in ICUs without sedation protocols compared with ICUs with protocols1 • Use of sedation protocols and scores increased between 2002 and 20062 Assessed Treated * Patients (%) * Protocol No Protocol * P < 0.01 vs ICUs using a protocol 1. Payen JF, et al. Anesthesiol. 2007;106:687-695. 2. Martin J, et al. Crit Care. 2007;11:R124.
Cardinal Symptoms of Delirium and Coma Morandi A, et al. Intensive Care Med. 2008;34:1907-1915.
ICU Delirium • Develops in ~2/3 of critically ill patients • Hypoactive or mixed forms most common • Increased risk • Benzodiazepines • Extended ventilation • Immobility • Associated with weakness • Undiagnosed in up to 72% of cases Vasilevskis EE, et al. Chest. 2010;138(5):1224-1233.
Patient Factors Increased age Alcohol use Male gender Living alone Smoking Renal disease Predisposing Disease Cardiac disease Cognitive impairment (eg, dementia) Pulmonary disease Less Modifiable • Acute Illness • Length of stay • Fever • Medicine service • Lack of nutrition • Hypotension • Sepsis • Metabolic disorders • Tubes/catheters • Medications: • Anticholinergics • Corticosteroids • - Benzodiazepines DELIRIUM Environment Admission via ED or through transfer Isolation No clock No daylight No visitors Noise Use of physical restraints More Modifiable Van Rompaey B, et al. Crit Care. 2009;13:R77. Inouye SK, et al. JAMA.1996;275:852-857. Skrobik Y. Crit Care Clin. 2009;25:585-591.
Sequelae of Delirium • Increased mortality • Longer intubation time • Average 10 additional days in hospital • Higher costs of care During the ICU/Hospital Stay • Increased mortality • Development of dementia • Long-term cognitive impairment • Requirement for care in chronic care facility • Decreased functional status at 6 months After Hospital Discharge Bruno JJ, Warren ML. Crit Care Nurs Clin North Am. 2010;22(2):161-178. Shehabi Y, et al. Crit Care Med. 2010;38(12):2311-2318. Rockwood K, et al. Age Ageing. 1999;28(6):551-556. Jackson JC, et al. Neuropsychol Rev. 2004;14:87-98. Nelson JE, et al. Arch Intern Med. 2006;166:1993-1999.
Delirium Duration and Mortality Kaplan-Meier Survival Curve P < 0.001 Each day of delirium in the ICU increases the hazard of mortality by 10% Pisani MA. Am J Respir Crit Care Med. 2009;180:1092-1097.
Confusion Assessment Method(CAM-ICU) 1. Acute onset of mental status changes or a fluctuating course and 2. Inattention and 4. Disorganized thinking 3. Altered level of consciousness or = Delirium Ely EW, et al. Crit Care Med. 2001;29:1370-1379. Ely EW, et al. JAMA. 2001;286:2703-2710.
Intensive Care Delirium Screening Checklist 1. Altered level of consciousness 2. Inattention 3. Disorientation 4. Hallucinations 5. Psychomotor agitation or retardation 6. Inappropriate speech 7. Sleep/wake cycle disturbances 8. Symptom fluctuation • Score 1 point for each component present during shift • Score of 1-3 = Subsyndromal Delirium • Score of ≥ 4 = Delirium Bergeron N, et al. Intensive Care Med. 2001;27:859-864. Ouimet S, et al. Intensive Care Med. 2007;33:1007-1013.
Subsyndromal Delirium and Clinical Outcomes *Pairwise comparison Ouimet S, et al. Intensive Care Med. 2007;33:1007-1013.
What to THINK When Delirium Is Present • Toxic Situations • CHF, shock, dehydration • Deliriogenic meds (Tight Titration) • New organ failure, eg, liver, kidney • Hypoxemia; also, consider giving Haloperidol or other antipsychotics? • Infection/sepsis (nosocomial), Immobilization • Nonpharmacologic interventions • Hearing aids, glasses, reorient, sleep protocols, music, noise control, ambulation • K+ or Electrolyte problems See Skrobik Y. Crit Care Clin. 2009;25:585-591.
Oversedation • Prolonged mechanical ventilation • Increase length of stay • Increased risk of complications • - Ventilator-associated pneumonia • Increased diagnostic testing • Inability to evaluate for delirium ICU Sedation: The Balancing Act Patient Comfort and Ventilatory Optimization G O A L Undersedation • Patient recall • Device removal • Ineffectual mechanical ventilation • Initiation of neuromuscular blockade • Myocardial or cerebral ischemia • Decreased family satisfaction w/ care Jacobi J, et al. Crit Care Med. 2002;30:119-141.
Consequence of Improper Sedation • Continuous sedation carries the risks associated with oversedation and may increase the duration of mechanical ventilation (MV)1 • MV patients accrue significantly more cost during their ICU stay than non-MV patients2 • $31,574 versus $12,931, P < 0.001 • Sedation should be titrated to achieve a cooperative patient and daily wake-up, a JC requirement1,2 15.4% 30.6% 54.0% Undersedated3 Oversedated On Target 1. Kress JP, et al. N Engl J Med. 2000;342:1471-1477. 2. Dasta JF, et al. Crit Care Med. 2005;33:1266-1271. 3. Kaplan LJ, Bailey H.Crit Care. 2000;4(suppl 1):P190.
Opioids Clinical Effects Adverse Effects • Respiratory depression • Analgesia • Sedation • Hypotension • Bradycardia • Constipation • Tolerance Fentanyl • Withdrawal symptoms • Hormonal changes Morphine Remifentanil Benyamin R, et al. Pain Physician. 2008;11(2 Suppl):S105-120.
Opioid Mechanisms Neurotransmitters ACh Acetylcholine Glu Glutamate NE Norepinephrine Brown EN, et al. N Engl J Med. 2010;363(27):2638-2650.
Analgosedation Analgesic first (A-1), supplement with sedative Acknowledges that discomfort may cause agitation Remifentanil-based regimen Reduces propofol use Reduces median MV time Improves sedation-agitation scores Not appropriate for drug or alcohol withdrawal Park G, et al. Br J Anaesth. 2007;98:76-82. Rozendaal FW, et al. Intensive Care Med. 2009;35:291-298.
Analgosedation • 140 critically ill adult patients undergoing mechanical ventilation in single center • Randomized, open label trial • Both groups received bolus morphine (2.5 or 5 mg) • Group 1: No sedation (n = 70 patients)- morphine prn • Group 2: Sedation (20 mg/mL propofol for 48 h, 1 mg/mL midazolam thereafter) with daily interruption until awake (n = 70, control group) • Endpoints • Primary • Number of days without mechanical ventilation in a 28-day period • Other • Length of stay in ICU (admission to 28 days) • Length of stay in hospital (admission to 90 days) Strøm T, et al. Lancet. 2010;375:475-480.
Analgosedation Intervention Morphine prn at 2.5 or 5 mg for comfort Physician consult if patient seemed uncomfortable Haloperidol prnfor delirium If still uncomfortable, propofol infusion for 6 hours Transitioned back to prn morphine Strøm T, et al. Lancet. 2010;375:475-480.
AnalgosedationResults • Patients receiving no sedation had • More days without ventilation (13.8 vs 9.6 days, P = 0.02) • Shorter stay in ICU (HR 1.86, P = 0.03) • Shorter stay in hospital (HR 3.57, P = 0.004) • More agitated delirium (N = 11, 20% vs N = 4, 7%, P = 0.04) • No differences found in • Accidental extubations • Need for CT or MRI • Ventilator-associated pneumonia Strøm T, et al. Lancet. 2010;375:475-480.
Characteristics of an Ideal Sedative Rapid onset of action allows rapid recovery after discontinuation Effective at providing adequate sedation with predictable dose response Easy to administer Lack of drug accumulation Few adverse effects Minimal adverse interactions with other drugs Cost-effective Promotes natural sleep 1. Ostermann ME, et al. JAMA. 2000;283:1451-1459. 2. Jacobi J, et al. Crit Care Med. 2002;30:119-141. 3. Dasta JF, et al. Pharmacother. 2006;26:798-805. 4. Nelson LE, et al. Anesthesiol. 2003;98:428-436.
Consider Patient Comorbidities When Choosing a Sedation Regimen • Chronic pain • Organ dysfunction • CV instability • Substance withdrawal • Respiratory insufficiency • Obesity • Obstructive sleep apnea
GABA Agonist Benzodiazepine Midazolam Clinical Effects Adverse Effects • Sedation, anxiolysis, and amnesia • Rapid onset of action (IV) • May accumulate with hepatic and/or renal failure • Anterograde amnesia • Long recovery time • Synergy with opioids • Respiratory depression • Delirium Olkkola KT, Ahonen J. Handb Exp Pharmacol. 2008;(182):335-360. Riker RR, et al; SEDCOM Study Group. JAMA. 2009;301(5):489-499.
Midazolam Pharmacodynamics: It’s About Time • Highly lipid soluble • α-OH midazolam metabolite • CYP3A4 activity decreased in critical illness • Substantial CYP3A4 variability 60 50 40 Time to Endpoint (h) Extubation 30 Alertness Recovery 20 10 0 Sedation Time (days) < 1 1-7 > 7 Carrasco G, et al. Chest. 1993;103:557-564. Bauer TM, et al. Lancet. 1995;346:145-147.
GABA Agonist Benzodiazepine Lorazepam • Adverse Effects • Metabolic acidosis (propylene glycol vehicle toxicity) • Retrograde and anterograde amnesia • Delirium Clinical Effects • Sedation, anxiolysis, and amnesia • Commonly used for long-term sedation Olkkola KT, Ahonen J. Handb Exp Pharmacol. 2008;(182):335-360. Wilson KC, et al. Chest. 2005;128(3):1674-1681.
Risk of Delirium With Benzodiazepines Delirium Risk Lorazepam Dose, mg Pandharipande P, et al. J Trauma. 2008;65:34-41. Pandharipande P, et al. Anesthesiol. 2006:104:21-26.
GABA Agonist Propofol Clinical Effects Adverse Effects • Sedation • Hypnosis • Anxiolysis • Muscle relaxation • Mild bronchodilation • Decreased ICP • Decreased cerebral metabolic rate • Antiemetic • Pain on injection • Respiratory depression • Hypotension • Decreased myocardial contractility • Increased serum triglycerides • Tolerance • Propofol infusion syndrome • Prolonged effect with high adiposity • Seizures (rare) Ellett ML. Gastroenterol Nurs. 2010;33(4):284-925. Lundström S, et al. J Pain Symptom Manage. 2010;40(3):466-470.
Central Mechanisms of Propofol Monoaminergic pathways Cholinergic pathways Lateral hypothalamus neurons Neurotransmitters ACh Acetylcholine DA Dopamine GABA γ-Aminobutyric acid GAL Galanin Glu Glutamate His Histamine NE Norepinephrine 5HT Serotonin Brown EN, et al. N Engl J Med. 2010;363(27):2638-2650.
Propofol Has Greater Sedation Efficacy Than Continuous Midazolam Duration of Adequate Sedation Efficacy of Sedation* n = 18 trials n = 15 trials * Avg adequate sedation time avg total sedation time Walder B, et al. Anesth Analg. 2001;92:975-983.