Connee L. Sloman, CRNA Certified Registered Nurse Anesthetist Associated Anesthesiologist Springfield, Illinois Assessing and Managing Sedation
Faculty Disclosure It is the policy of The France Foundation to ensure balance, independence, objectivity, and scientific rigor in all its sponsored educational activities. All faculty, activity planners, content reviewers, and staff participating in this activity will disclose to the participants any significant financial interest or other relationship with manufacturer(s) of any commercial product(s)/device(s) and/or provider(s) of commercial services included in this educational activity. The intent of this disclosure is not to prevent a person with a relevant financial or other relationship from participating in the activity, but rather to provide participants with information on which they can base their own judgments. The France Foundation has identified and resolved any and all conflicts of interest prior to the release of this activity. Connee Sloman, CRNA, has received grant/research support from the AANA.
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 pain, agitation, and delirium management and incorporate them into the management of ICU patients
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 –Delirium –Anxiety Avoid post-intensive care syndrome 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.
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 abuse/withdrawal Respiratory insufficiency Obesity Obstructive sleep apnea
Potential Drawbacks of Sedative and Analgesic Therapy Impede assessment of neurologic function Increase risk for delirium Numerous agent-specific adverse events Vital signs alone do not tell the amount of pain Need for objective measures of brain function to adjunctively monitor level of consciousness especially with NDNMB (BIS) Kollef MH, et al. Chest. 1998;114:541-548. Pandharipande PP, et al. Anesthesiology. 2006;104:21-26.
A Word About the 2013 PAD Guidelines (Evidence-based) Supporting organizations –American College of Critical Care Medicine (ACCM) –Society of Critical Care Medicine (SCCM) –American Society of Health-System Pharmacists (ASHP) Suggest preemptively treating pain with analgesics and/or non-pharmacologic treatment Use opioids as first-line therapy for treatment of non- neuropathic pain Use non-opioid analgesics in conjunction with opioids to decrease opioid requirements and side effects
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 patients 2 –$31,574 versus $12,931, P < 0.001 Sedation should be titrated to achieve a cooperative patient and daily wake-up, a JC requirement 1,2 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. Undersedated 3 Oversedated On Target 15.4% 54.0% 30.6%
Pain, Agitation, and Delirium Are Interrelated Barr J, et al. Crit Care Med. 2013;41:263-306. Agitation Pain Delirium
ICU Delirium Vasilevskis EE, et al. Chest. 2010;138(5):1224-1233. 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
After Hospital Discharge During the ICU/Hospital Stay Sequelae of Delirium Increased mortality Longer intubation time Average 10 additional days in hospital Higher costs of care Increased mortality Development of dementia Long-term cognitive impairment Requirement for care in chronic care facility Decreased functional status at 6 months 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.
Worse Long-term Cognitive Performance Duration of delirium was an independent predictor of cognitive impairment –An increase from 1 day of delirium to 5 days was associated with nearly a 5-point decline in cognitive battery scores Patient testimony “One quite literally loses one’s grip on what is true and what is false because the true and the false are mixed together in a mess of experience.” Girard TD, et al. Crit Care Med. 2010;38:1513-1520. Misak CJ. Am J Respir Crit Care Med. 2004;170(4):357-359.
Consequences of Delirium After Cardiac Operations Delirium after cardiac procedures is associated with –Increased mortality (13.5% vs 2.0% in patients without) –More hospital readmissions (45.7% vs 26.5%) –Reduced quality of life –Reduced cognitive functioning, including failures in attention, memory, perception, and motor function, and with functional dysfunction such as independency in activities of daily living and mobility Suggests we need new treatment strategies Koster S, et al. Ann Thorac Sur. 2012;93:705-711.
To determine the efficacy and safety of a protocol linking: spontaneous awakening trials (SATs) & spontaneous breathing trials (SBTs) –Ventilator-free days –Duration of mechanical ventilation –ICU and hospital length of stay –Duration of coma and delirium –Long-term neuropsychological outcomes ABC Trial: Objectives Girard TD, et al. Lancet. 2008;371:126-134.
A Clinical Approach to Improve Outcomes in Critically Ill Patients More than half of patients on MV in the United States receive continuous sedation –Risks (delirium, prolonged MV, ↑ stay ICU/hospital) –Benzodiazepines and propofol DIS (daily interruption of sedation) Evidence suggests DIS used with assessment tools can lead to improved outcomes Despite recommendations less than 33% of Medical ICUs in the US use a sedation protocol Berry E, Zecca H. Crit Care Nurse. 2012;32(1):43-51.
Despite Proven Benefits, Spontaneous Awakening/Daily Interruption Trials Are Not Standard of Practice at Most Institutions Canada – 40% get SATs (273 physicians in 2005) 1 US – 40% get SATs (2004-05) 2 Germany – 34% get SATs (214 ICUs in 2006) 3 France – 40–50% deeply sedated with 90% on continuous infusion of sedative/opiate 4 1. Mehta S, et al. Crit Care Med. 2006;34:374-380. 2. Devlin J. Crit Care Med. 2006;34:556-557. 3. Martin J, et al. Crit Care. 2007;11:R124. 4. Payen JF, et al. Anesthesiology. 2007;106:687-695.
Correlating Pain Assessment With Analgesic Administration in the ICU Fewer patients assessed for pain, more treated with analgesics in ICUs without analgesia protocols compared with ICUs with protocols 1 Pain scoring used in 21% of surveyed ICUs in 2006 2 1. Payen JF, et al. Anesthesiol. 2007;106:687-695. 2. Martin J, et al. Crit Care. 2007;11:R124. Patients (%) ProtocolNo Protocol Assessed Treated * P < 0.01 vs ICUs using a protocol * *
Common Agents for Conscious Sedation Mustoe TA, et al. Plast Reconstr Surg. 2010;126(4):165e-176e. AgentClassificationDose Guidelines Side Effects MidazolamBZD0.5-1 mg every 5-10 min Respiratory depression, somnolence KetamineDissociative Anesthetic 200-750 mcg/kg bolus, 5-20 mcg/kg/min Hallucinations, delirium, intracranial HTN, ↑ secretions FentanylOpioid agonist25-50 mcgRespiratory depression, Nausea/vomiting
Sedation-Agitation Scale (SAS) Riker RR, et al. Crit Care Med. 1999;27:1325-1329. Brandl K, et al. Pharmacotherapy. 2001;21:431-436.
PAD Choice of Sedative Recommendations We suggest that analgesia-first sedation be used in mechanically ventilated adult ICU patients (+2B) We suggest that sedation strategies using nonbenzodiazepine sedatives (either propofol or dexmedetomidine) may be preferred over sedation with benzodiazepines (either midazolam or lorazepam) to improve clinical outcomes in mechanically ventilated adult ICU patients (+2B) We suggest that in adult ICU patients with delirium unrelated to alcohol or benzodiazepine withdrawal, continuous IV infusions of dexmedetomidine rather than benzodiazepine infusions be administered for sedation to reduce the duration of delirium in these patients (+2B) Barr J, et al. Crit Care Med. 2013;41:263-306.
Ramsay Sedation Scale 1 - Awake and anxious, agitated, or restless 2 - Awake, cooperative, accepting ventilation, oriented, tranquil 3 - Awake; responds only to commands 4 - Asleep; brisk response to light glabellar tap or loud noise 5 - Asleep; sluggish response to light glabellar tap or loud noise stimulus but does not respond to painful stimulus 6 - Asleep; no response to light glabellar tap or loud noise Ramsay MA, et al. Br Med J. 1974;2(5920):656-659.
GABA Agonist Benzodiazepine (Midazolam) May accumulate with hepatic and/or renal failure Anterograde amnesia Long recovery time Synergy with opioids Respiratory depression Delirium Sedation, anxiolysis, and amnesia Rapid onset of action (IV) Adverse EffectsClinical Effects Olkkola KT, Ahonen J. Handb Exp Pharmacol. 2008;(182):335-360. Riker RR, et al; SEDCOM Study Group. JAMA. 2009;301(5):489-499.
Agonist Dexmedetomidine Hypotension Hypertension Nausea Bradycardia Dry mouth Peripheral vasoconstriction at high doses Antihypertensive Sedation Analgesia Decreased shivering Anxiolysis Patient arousability Potentiate effects of opioids, sedatives, and anesthetics Decrease sympathetic activity Adverse Effects Clinical Effects Kamibayashi T, et al. Anesthesiol. 2000;93:1345-1349. Bhana N, et al. Drugs. 2000;59(2):263-268.
Benzodiazepines vs Propofol Better Outcomes With Propofol Study/YearPopulationOutcome Improved Grounds et al 1987Cardiac surgeryFaster awakening Aitkenhead et al 1989General ICUMore consistent awakening, faster weaning McMurray et al 1990Cardiac surgeryFaster awakening Carrasco et al 1993General ICU More accurate sedation, faster awakening, lower costs Roekaerts et al 1993Cardiac surgeryFaster awakening, earlier extubation Ronan et al 1995Surgical ICUFaster awakening Sherry et al 1996Cardiac surgeryLower costs Chamorro et al 1996General ICU Better ventilator synchrony, faster awakening Barrientos-Vega et al 1997General ICUEarlier extubation Weinbroum et al 1997General ICUFaster awakening Sanchez-Izquierdo-Riera et al 1998Trauma ICUFaster awakening McCollam et al 1999Trauma ICULess oversedation Hall et al 2001Mixed ICUMore accurate sedation, earlier extubation Carson et al 2006Medical ICUFewer ventilator days Ely EW, et al. Chest. 2012;142(2);287-289.
Benzodiazepines vs Propofol Study/YearPopulationOutcome Improved Trials finding no differences in outcomes Searle et al, 1997 Cardiac surgeryNone Kress et al, 2000 Medical ICUNone Huey-Ling et al, 2008 Cardiac surgeryNone Trials finding better outcomes with benzodiazepine: None Ely EW, et al. Chest. 2012;142(2);287-289.
Benzodiazepines vs Dexmedetomidine Study/YearPopulationOutcome Improved Trials finding better outcomes with dex Pandharipande et al, 2007 Mixed ICUMore accurate sedation, more delirium/coma-free days Riker et al, 2009 Mixed ICULower prevalence of delirium, earlier extubation Ruokonen et al, 2009 Mixed ICUShorter duration of mechanical ventilation Maldonado et al, 2009 Cardiac surgeryLower incidence and duration of delirium Esmaoglu et al, 2009 EclampsiaShorter ICU length of stay Dasta et al, 2010 Mixed ICULower ICU costs Jakob et al, 2012 General ICULighter sedation, fewer ventilation days Trials finding no differences in outcomes: None Trials finding better outcomes with the BZD: None Ely EW, et al. Chest. 2012;142(2);287-289.
MENDS: Dexmedetomidine vs Lorazepam Pandharipande PP, et al. JAMA. 2007;298(22):2644-2653. Double-blind RCT of dex (0.15–1.5 mcg/kg/hr) vs lorazepam (1–10 mg/hr) Titrated to sedation goal (using RASS) established by ICU team Dexmedetomidine resulted in more time spent within sedation goals than lorazepam (P = 0.04). Differences in 28-day mortality and delirium-free days were not significant While incidence of HR ≤ 60 was greater with Dex (17 vs 4%, P = 0.03, the incidence of HR ≤ 40 was not different (2 vs 2%)
Double-blind, randomized, multicenter trial comparing long-term (> 24 hr) dexmedetomidine (n = 244) with midazolam (n = 122) Sedatives (DEX 0.2-1.4 μg/kg/hr or MDZ 0.02-0.1 mg/kg/hr) titrated for light sedation (RASS -2 to +1), administered up to 30 days All patients underwent daily arousal assessments and drug titration Q 4 hours Riker RR, et al. JAMA. 2009;301(5):489-499. Outcome Midazolam (N = 122) DEX (N = 244) P- Value Time in target sedation range, %188.8.131.52 Duration of sedation, days4.13.50.01 Time to extubation, days5.63.70.01 Patients receiving open-label, % midazolam 49630.02 Bradycardia, % 18.942.20.001 Bradycardia requiring intervention, %0.8 4.9 0.07 SEDCOM: Dexmedetomidine vs Midazolam
? 2A 2C 2A Anxiolysis 2B 2B X X Adapted from Kamibayashi T, Maze M. Anesthesiology. 2000;93:1346-1349. Physiology of Adrenoceptors 2A
Applications for a 2 Agonist Surgical –Bariatric surgery –CV surgery –Neurosurgery Endoscopic –Bronchoscopy –Fiberoptic intubation –Colonoscopy
35 Randomized, prospective, double-blind, placebo-controlled, multicenter 326 pts undergoing MAC for surgery (orthopedic, ophthalmic, vascular, excision of lesions, others < 10%) All patients sedated –Observer’s Assessment of Alertness/Sedation Scale (OAA/S ) to < 4 Sedation with –Dexmedetomidine ± rescue midazolam –Placebo + rescue midazolam Fentanyl PRN for pain MAC with Dexmedetomidine Candiotti KA, et al; MAC Study Group. Anesth Analg. 2010;110(1):47-56. MAC = Monitored anesthesia care
* * Midazolam UseFentanyl Use Dexmedetomidine Reduces Fentanyl and Midazolam Use During MAC *P < 0.001 compared with placebo, MAC = monitored anesthesia care ** * * * * Candiotti KA, et al; MAC Study Group. Anesth Analg. 2010;110(1):47-56.
Drugs for Fiberoptic Intubation Agent Class ExampleAdvantagesConsiderations GABA agonist Benzodiazepine Midazolam Quick onset Injection not painful Short duration Not analgesic Airway reflexes persist GABA agonist Benzodiazepine Propofol Quick onsetRespiratory depression Unconsciousness Decreased blood pressure & CO Increased HR OpioidFentanyl Remifentanil Analgesic Cough suppressive Respiratory depression 2 Agonist DexmedetomidinePt easily arousable Anxiolytic Analgesic No resp depression Transient hypertension Hypotension Bradycardia Summary courtesy of Pratik Pandharipande, MD.
Dexmedetomidine Increases Comfort in AFOI Double-blinded randomized trial Midazolam +/- dexmedetomidine Awake fiberoptic intubation (AFOI) Patient comfort rated by 2 observers Bergese SD, et al. J Clin Anesth. 2010;22(1):35-40. Total Comfort Score (max = 35) Pre- oxygenation Introduction of scope Introduction of ET tube n = 24 n = 31
Sedation for AFOI Conclusions Compared to placebo, dexmedetomidine reduces the amount of BZD in patients with high risk airway compromise in AFOI Dexmedetomidine in combination with low doses of midazolam is more effective than midazolam alone for sedation in AFOI
Fentanyl vs Dexmedetomidine in Bariatric Surgery 20 morbidly obese patients Roux-en-Y gastric bypass surgery All received midazolam, desflurane to maintain BIS at 45–50, and intraoperative analgesics –Fentanyl (n = 10) 0.5 µg/kg bolus, 0.5 µg/kg/h (group 1) –Dexmedetomidine (n = 10) 0.5 µg/kg bolus, 0.4 µg/kg/h (group 2) Dexmedetomidine associated with –Lower desflurane requirement for BIS maintenance –Decreased surgical BP and HR –Lower postoperative pain and morphine use (up to 2 h) Feld JM, et al. J Clin Anesthesia. 2006;18:24-28.
Dexmedetomidine in Bariatric Surgery 80 morbidly obese patients Gastric banding or gastric bypass surgery Prospective dose ranging study Medication –Celecoxib 400 mg po –Midazolam 20 µg/kg IV –Propofol 1.25 mg/kgIV –Desflurane 4% inspired –Dexmedetomidine 0, 0.2, 0.4, 0.8 µg/kg/h IV Tufanogullari B, et al. Anesth Analg. 2008;106:1741-1748.
Dexmedetomidine in Bariatric Surgery: Results More dex 0.8 patients required rescue phenylephrine for hypotension than control pts (50% vs 20%, P < 0.05) All dex groups –Required less desflurane (19–22%) –Had lower MAP for 45’ post-op –Required less fentanyl after awakening (36–42%) –Had less emetic symptoms post-op No clinical difference –Emergence from anesthesia –Post-op self-administered morphine and pain scores –Length of stay in post-anesthesia care unit –Length of stay in hospital Tufanogullari B, et al. Anesth Analg. 2008;106:1741-1748.
Neurological Surgery Desirable Properties for Sedatives Preservation of intracranial hemodynamics Hemodynamic stability Noninterference with neurophysiologic monitoring Cooperative sedation (for functional neurosurgery) Controllability (rapid onset and offset of effect) Neuroprotection Decreased awareness (by the patient) Decrease oxygen consumption
Characteristics of Cooperative Sedation for Neurosurgery Patients easily transition from sleep to wakefulness and task performance when aroused Patients can resume rest when not stimulated Most useful during procedures in which communication with the patient must be maintained, facilitates patient participation in therapeutic maneuvers Reduces risk of drug-induced complications Bekker A, et al. Neurosurgery. 2005;57(1 Suppl):1-10.
Current Sedatives for Awake Craniotomy Bonhomme V, et al. Eur J Anaesthesiol. 2009;26(11):906-912.
Sedation During Awake Craniotomy Is Dex Compatible With Neurocognitive Testing? Bekker 2001Bustillo 2002Lotto 2003Ard 2003Ard 2005 Patient Number1511217 IndicationNeoplasmAVM Tumor, epilepsy, aneurysm Pediatric epilepsyTumor, epilepsy Dex Load, μg/kg10 or 110.5 Dex Infusion, μg/kg.h0.4, 0.2, 0.10.2–0.70.60.5, 0.2, 0.10.1–0.4 Mean MDZ, mg2.811.7 (in 6 pts) Mean Fentanyl, μg100160100191 (in 16 pts) Other AnesthesiaProp, N 2 O, Sevo(flumazenil)PropProp, N 2 O, sevo Cognitive TestLanguageWadaLanguage Test successful?1/10/510/112/217/17 Bekker AY, et al. Anesth Analg. 2001;92(5):1251-1253. Bustillo MA, et al. J Neurosurg Anesthesiol. 2002;14(3):209-212. Lotto M, et al. Anesthesiology. 2003; 99: A356. Ard J, et al. J Neurosurg Anesthesiol. 2003;15(3):263-266. Ard JL, et al. Surg Neurol. 2005;63(2):114-116. AVM = arteriovenous malformation Prop = propofol Sevo = sevoflurane
Implanting Deep Brain Stimulator for Parkinson’s Disease Sedation is demanding –Recordings of movement-related neurons –Preservation of Parkinson’s symptoms for DBS localization –Patient cooperation –Halo restricts movement, respiratory depression problematic GABAergic sedatives (MDZ, propofol) not useful –Ameliorate tremor and rigidity (precludes mapping & testing) –Impair consciousness –May cause respiratory depression Rozet I, et al. Anesth Analg. 2006;103(5):1224-1228.
Implanting Deep Brain Stimulator for Parkinson’s Disease Retrospective study with dexmedetomidine –Control (no sedative) n = 8 patients –Dex (0.1-0.3 mcg/kg.h, more to goal [OAA/S = 4])n = 11 patients Results –Microelectrode recordings unimpaired by dex –Surgical time shorter with dex (4 vs 6 h, P = 0.05) –Less intraoperative use of antihypertensives (100% vs 54%, P = 0.048) –Dex preserved clinical signs of Parkinson’s disease Tremor Rigidity Bradykinesia Study limitations –Small –Observational –Only perioperative outcomes presented Rozet I, et al. Anesth Analg. 2006;103(5):1224-1228.
Implanting Deep Brain Stimulator for Parkinson’s Disease Retrospective analysis of 258 procedures (250 patients) Patients with motor disorders, 68% PD Propofol most common sedative, 91% Propofol used almost exclusively in the first 30 to 45 minutes to facilitate head-frame placement Khatib R, et al. J Neurosurg Anesthesiol. 2008;20:36-40.
Neurosurgery Summary Neurosurgery presents special challenges for sedation –Preserve cerebral hemodynamic stability –Maintain patient consciousness for some procedures Oversedation presents risks –Delirium –Increased ICU LOS –Lack of patient interaction during procedure Emerging combinations of anesthetic and sedative compounds have attractive properties for addressing these unique requirements
Case Presentation 64-year-old female with pulsatile mass left shoulder 67-year-old severe pump failure with poor prognosis 71-year-old BZD and opioid dependent female for MVR Penney R. AANA J. 2010;78(6):446-450.