Sedative-analgesic medications in critically ill adults: Selection, initiation, maintenance, and withdrawal
- Barry Fuchs, MD
Barry Fuchs, MD
- Associate Professor of Medicine
- University of Pennsylvania School of Medicine
- Cassandra Bellamy, PharmD, BCPS
Cassandra Bellamy, PharmD, BCPS
- Clinical Pharmacy Specialist, Medical Intensive Care Unit
- Hospital of the University of Pennsylvania
- Section Editors
- Polly E Parsons, MD
Polly E Parsons, MD
- Editor-in-Chief — Pulmonary and Critical Care Medicine
- Section Editor — Critical Care
- Professor of Medicine
- University of Vermont College of Medicine
- Michael Avidan, MD
Michael Avidan, MD
- Section Editor — Surgical Critical Care
- Professor of Anesthesiology and Surgery
- Washington University School of Medicine
Distress generally presents as agitation. It is common among critically ill patients, especially those who are intubated or having difficulty communicating with their caregivers . Distress needs to be treated for patient comfort and because it increases sympathetic tone, which may have untoward physiological effects . Barring few exceptions (eg, neuromuscular paralysis, procedures) the administration of sedative-analgesic medications should not be based on anticipated distress but rather on that which is observed; otherwise, there will be an increased risk of over sedation which has been shown to worsen clinical outcomes.
The management of agitation in critically ill adults is reviewed here, including the initiation, maintenance, and withdrawal of pharmacological sedation. Common sedative-analgesic medications, the treatment of pain, and the use of neuromuscular blocking medications in critically ill patients are discussed elsewhere. (See "Sedative-analgesic medications in critically ill adults: Properties, dosage regimens, and adverse effects" and "Pain control in the critically ill adult patient" and "Use of neuromuscular blocking medications in critically ill patients".)
Before a sedative-analgesic agent is initiated to manage agitation, the cause of the distress should be identified and treated. Nonpharmacological strategies are preferred and should be implemented prior to the use of pharmacologic treatment.
Identify the cause of distress — Common causes of distress in critically ill patients include anxiety, pain, delirium, dyspnea, and neuromuscular paralysis. These etiologies may occur separately or in combination.
●Anxiety – Anxiety is defined as a sustained state of apprehension and autonomic arousal in response to real or perceived threats . Fear of suffering, fear of death, loss of control, and frustration due to the inability to effectively communicate are typical causes of anxiety in critically ill patients. Symptoms and signs include headache, nausea, insomnia, anorexia, dyspnea, palpitations, dizziness, dry mouth, chest pain, diaphoresis, hyperventilation, pallor, tachycardia, tremulousness, and/or hypervigilance.
Identifying and treating the proximate cause of anxiety is always ideal as it may ameliorate both problems. Dyspnea, for example, is a common underlying cause of anxiety among critically-ill patients. Thus, if inadequate ventilator flow is causing dyspnea with resultant anxiety, the ultimate treatment for the anxiety (and underlying dyspnea) may be adjustment of ventilator settings. Alternatively, the abrupt onset of anxiety may prompt further work-up for a cardiopulmonary source.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Hansen-Flaschen J. Improving patient tolerance of mechanical ventilation. Challenges ahead. Crit Care Clin 1994; 10:659.
- Lewis KS, Whipple JK, Michael KA, Quebbeman EJ. Effect of analgesic treatment on the physiological consequences of acute pain. Am J Hosp Pharm 1994; 51:1539.
- Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 2013; 41:263.
- Griffiths J, Hatch RA, Bishop J, et al. An exploration of social and economic outcome and associated health-related quality of life after critical illness in general intensive care unit survivors: a 12-month follow-up study. Crit Care 2013; 17:R100.
- Milbrandt EB, Deppen S, Harrison PL, et al. Costs associated with delirium in mechanically ventilated patients. Crit Care Med 2004; 32:955.
- McNicoll L, Pisani MA, Zhang Y, et al. Delirium in the intensive care unit: occurrence and clinical course in older patients. J Am Geriatr Soc 2003; 51:591.
- Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004; 291:1753.
- Klein Klouwenberg PM, Zaal IJ, Spitoni C, et al. The attributable mortality of delirium in critically ill patients: prospective cohort study. BMJ 2014; 349:g6652.
- Mehta S, Cook D, Devlin JW, et al. Prevalence, risk factors, and outcomes of delirium in mechanically ventilated adults. Crit Care Med 2015; 43:557.
- Aldemir M, Ozen S, Kara IH, et al. Predisposing factors for delirium in the surgical intensive care unit. Crit Care 2001; 5:265.
- Fontaine DK. Nonpharmacologic management of patient distress during mechanical ventilation. Crit Care Clin 1994; 10:695.
- Strøm T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet 2010; 375:475.
- Strøm T, Stylsvig M, Toft P. Long-term psychological effects of a no-sedation protocol in critically ill patients. Crit Care 2011; 15:R293.
- Chlan LL, Weinert CR, Heiderscheit A, et al. Effects of patient-directed music intervention on anxiety and sedative exposure in critically ill patients receiving mechanical ventilatory support: a randomized clinical trial. JAMA 2013; 309:2335.
- Bradt J, Dileo C. Music interventions for mechanically ventilated patients. Cochrane Database Syst Rev 2014; :CD006902.
- Wunsch H, Kahn JM, Kramer AA, Rubenfeld GD. Use of intravenous infusion sedation among mechanically ventilated patients in the United States. Crit Care Med 2009; 37:3031.
- Soro M, Gallego L, Silva V, et al. Cardioprotective effect of sevoflurane and propofol during anaesthesia and the postoperative period in coronary bypass graft surgery: a double-blind randomised study. Eur J Anaesthesiol 2012; 29:561.
- Roberts DJ, Haroon B, Hall RI. Sedation for critically ill or injured adults in the intensive care unit: a shifting paradigm. Drugs 2012; 72:1881.
- Kollef MH, Levy NT, Ahrens TS, et al. The use of continuous i.v. sedation is associated with prolongation of mechanical ventilation. Chest 1998; 114:541.
- Wittbrodt ET. The ideal sedation assessment tool: an elusive instrument. Crit Care Med 1999; 27:1384.
- Devlin JW, Boleski G, Mlynarek M, et al. Motor Activity Assessment Scale: a valid and reliable sedation scale for use with mechanically ventilated patients in an adult surgical intensive care unit. Crit Care Med 1999; 27:1271.
- Riker RR, Picard JT, Fraser GL. Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med 1999; 27:1325.
- Weinert C, McFarland L. The state of intubated ICU patients: development of a two-dimensional sedation rating scale for critically ill adults. Chest 2004; 126:1883.
- Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002; 166:1338.
- Ely EW, Truman B, Shintani A, et al. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA 2003; 289:2983.
- Bizek KS. Optimizing sedation in critically ill, mechanically ventilated patients. Crit Care Nurs Clin North Am 1995; 7:315.
- Ambuel B, Hamlett KW, Marx CM, Blumer JL. Assessing distress in pediatric intensive care environments: the COMFORT scale. J Pediatr Psychol 1992; 17:95.
- Olleveant N, Humphris G, Roe B. A reliability study of the modified new Sheffield Sedation Scale. Nurs Crit Care 1998; 3:83.
- Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxalone-alphadolone. Br Med J 1974; 2:656.
- Ely EW, Margolin R, Francis J, et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med 2001; 29:1370.
- Simmons LE, Riker RR, Prato BS, Fraser GL. Assessing sedation during intensive care unit mechanical ventilation with the Bispectral Index and the Sedation-Agitation Scale. Crit Care Med 1999; 27:1499.
- Deogaonkar A, Gupta R, DeGeorgia M, et al. Bispectral Index monitoring correlates with sedation scales in brain-injured patients. Crit Care Med 2004; 32:2403.
- Mondello E, Siliotti R, Noto G, et al. Bispectral Index in ICU: correlation with Ramsay Score on assessment of sedation level. J Clin Monit Comput 2002; 17:271.
- Frenzel D, Greim CA, Sommer C, et al. Is the bispectral index appropriate for monitoring the sedation level of mechanically ventilated surgical ICU patients? Intensive Care Med 2002; 28:178.
- Ely EW, Truman B, Manzi DJ, et al. Consciousness monitoring in ventilated patients: bispectral EEG monitors arousal not delirium. Intensive Care Med 2004; 30:1537.
- De Deyne C, Struys M, Decruyenaere J, et al. Use of continuous bispectral EEG monitoring to assess depth of sedation in ICU patients. Intensive Care Med 1998; 24:1294.
- Vivien B, Di Maria S, Ouattara A, et al. Overestimation of Bispectral Index in sedated intensive care unit patients revealed by administration of muscle relaxant. Anesthesiology 2003; 99:9.
- Dahaba AA. Different conditions that could result in the bispectral index indicating an incorrect hypnotic state. Anesth Analg 2005; 101:765.
- Shehabi Y, Chan L, Kadiman S, et al. Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study. Intensive Care Med 2013; 39:910.
- Shehabi Y, Bellomo R, Reade MC, et al. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med 2012; 186:724.
- Brook AD, Ahrens TS, Schaiff R, et al. Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Crit Care Med 1999; 27:2609.
- Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342:1471.
- Carson SS, Kress JP, Rodgers JE, et al. A randomized trial of intermittent lorazepam versus propofol with daily interruption in mechanically ventilated patients. Crit Care Med 2006; 34:1326.
- Schweickert WD, Gehlbach BK, Pohlman AS, et al. Daily interruption of sedative infusions and complications of critical illness in mechanically ventilated patients. Crit Care Med 2004; 32:1272.
- Balas MC, Vasilevskis EE, Olsen KM, et al. Effectiveness and safety of the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle. Crit Care Med 2014; 42:1024.
- Aitken LM, Bucknall T, Kent B, et al. Protocol-directed sedation versus non-protocol-directed sedation to reduce duration of mechanical ventilation in mechanically ventilated intensive care patients. Cochrane Database Syst Rev 2015; 1:CD009771.
- Collinsworth AW, Priest EL, Campbell CR, et al. A Review of Multifaceted Care Approaches for the Prevention and Mitigation of Delirium in Intensive Care Units. J Intensive Care Med 2016; 31:127.
- Girard TD, Kress JP, Fuchs BD, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet 2008; 371:126.
- Jackson JC, Girard TD, Gordon SM, et al. Long-term cognitive and psychological outcomes in the awakening and breathing controlled trial. Am J Respir Crit Care Med 2010; 182:183.
- Burry L, Rose L, McCullagh IJ, et al. Daily sedation interruption versus no daily sedation interruption for critically ill adult patients requiring invasive mechanical ventilation. Cochrane Database Syst Rev 2014; :CD009176.
- Minhas MA, Velasquez AG, Kaul A, et al. Effect of Protocolized Sedation on Clinical Outcomes in Mechanically Ventilated Intensive Care Unit Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Mayo Clin Proc 2015; 90:613.
- Mehta S, Burry L, Martinez-Motta JC, et al. A randomized trial of daily awakening in critically ill patients managed with a sedation protocol: a pilot trial. Crit Care Med 2008; 36:2092.
- Kher S, Roberts RJ, Garpestad E, et al. Development, implementation, and evaluation of an institutional daily awakening and spontaneous breathing trial protocol: a quality improvement project. J Intensive Care Med 2013; 28:189.
- Hager DN, Dinglas VD, Subhas S, et al. Reducing deep sedation and delirium in acute lung injury patients: a quality improvement project. Crit Care Med 2013; 41:1435.
- Mehta S, Burry L, Cook D, et al. Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA 2012; 308:1985.
- Devlin JW, Tanios MA, Epstein SK. Intensive care unit sedation: waking up clinicians to the gap between research and practice. Crit Care Med 2006; 34:556.
- Mehta S, Burry L, Fischer S, et al. Canadian survey of the use of sedatives, analgesics, and neuromuscular blocking agents in critically ill patients. Crit Care Med 2006; 34:374.
- Kress JP, Gehlbach B, Lacy M, et al. The long-term psychological effects of daily sedative interruption on critically ill patients. Am J Respir Crit Care Med 2003; 168:1457.
- Kress JP, Vinayak AG, Levitt J, et al. Daily sedative interruption in mechanically ventilated patients at risk for coronary artery disease. Crit Care Med 2007; 35:365.
- Cammarano WB, Pittet JF, Weitz S, et al. Acute withdrawal syndrome related to the administration of analgesic and sedative medications in adult intensive care unit patients. Crit Care Med 1998; 26:676.
- Honey BL, Benefield RJ, Miller JL, Johnson PN. Alpha2-receptor agonists for treatment and prevention of iatrogenic opioid abstinence syndrome in critically ill patients. Ann Pharmacother 2009; 43:1506.
- Al-Qadheeb NS, Roberts RJ, Griffin R, et al. Impact of enteral methadone on the ability to wean off continuously infused opioids in critically ill, mechanically ventilated adults: a case-control study. Ann Pharmacother 2012; 46:1160.
- Maccioli GA. Dexmedetomidine to facilitate drug withdrawal. Anesthesiology 2003; 98:575.
- Multz AS. Prolonged dexmedetomidine infusion as an adjunct in treating sedation-induced withdrawal. Anesth Analg 2003; 96:1054.
- Identify the cause of distress
- Treat the cause of distress
- Nonpharmacological strategies
- Available agents
- Selection of an agent
- Initial dose
- Sedation goal
- - Scoring systems
- - Limitations
- Avoid excess sedation
- - Intermittent infusions
- - Daily interruption
- SUMMARY AND RECOMMENDATIONS