Semin Respir Crit Care Med 2021; 42(01): 098-111
DOI: 10.1055/s-0040-1716736
Review Article

Optimal Sedation and Pain Management: A Patient- and Symptom-Oriented Paradigm

Yahya Shehabi
1   Monash Health School of Clinical Sciences, Monash University, Clayton, Victoria, Melbourne, Australia
2   Prince of Wales Clinical School of Medicine, University of New South Wales, Randwick, New South Wales, Sydney, Australia
,
Wisam Al-Bassam
1   Monash Health School of Clinical Sciences, Monash University, Clayton, Victoria, Melbourne, Australia
,
Adrian Pakavakis
1   Monash Health School of Clinical Sciences, Monash University, Clayton, Victoria, Melbourne, Australia
,
Brendan Murfin
1   Monash Health School of Clinical Sciences, Monash University, Clayton, Victoria, Melbourne, Australia
,
Belinda Howe
3   The Australian and New Zealand Intensive Care Research Centre, Monash University, School of Public Health and Preventive Medicine, Melbourne, Victoria, Australia
› Author Affiliations

Abstract

In the critically ill patient, optimal pain and sedation management remains the cornerstone of achieving comfort, safety, and to facilitate complex life support interventions. Pain relief, using multimodal analgesia, is an integral component of any orchestrated approach to achieve clinically appropriate goals in critically ill patients. Sedative management, however, remains a significant challenge. Subsequent studies including most recent randomized trials have failed to provide strong evidence in favor of a sedative agent, a mode of sedation or ancillary protocols such as sedative interruption and sedative minimization. In addition, clinical practice guidelines, despite a comprehensive evaluation of relevant literature, have limitations when applied to individual patients. These limitations have been most apparent during the coronavirus disease 2019 pandemic. As such, there is a need for a mindset shift to a practical and achievable sedation strategy, driven by patients' characteristics and individual patient needs, rather than one cocktail for all patients. In this review, we present key principles to achieve patient-and symptom-oriented optimal analgesia and sedation in the critically ill patients. Sedative intensity should be proportionate to care complexity with due consideration to an individual patient's modifiers. The use of multimodal analgesics, sedatives, and antipsychotics agents—that are easily titratable—reduces the overall quantum of sedatives and opioids, and reduces the risk of adverse events while maximizing clinical benefits. In addition, critical considerations regarding the choice of sedative agents should be given to factors such as age, medical versus operative diagnosis, and cardiovascular status. Specific populations such as trauma, neurological injury, and pregnancy should also be taken into account to maximize efficacy and reduce adverse events.



Publication History

Article published online:
21 September 2020

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Vincent J-L, Shehabi Y, Walsh TS. et al. Comfort and patient-centred care without excessive sedation: the eCASH concept. Intensive Care Med 2016; 42 (06) 962-971
  • 2 Mehta S, Spies C, Shehabi Y. Ten tips for ICU sedation. Intensive Care Med 2017; 1-3
  • 3 Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342 (18) 1301-1308
  • 4 Guérin C, Reignier J, Richard J-C. et al; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013; 368 (23) 2159-2168
  • 5 Moss M, Huang DT, Brower RG. et al; National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. Network BIPCT. Early neuromuscular blockade in the acute respiratory distress syndrome. N Engl J Med 2019; 380 (21) 1997-2008
  • 6 Papazian L, Forel J-M, Gacouin A. et al; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 2010; 363 (12) 1107-1116
  • 7 Devlin JW, Skrobik Y, Gélinas C. et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med 2018; 46 (09) e825-e873
  • 8 Ely EW. The ABCDEF bundle: science and philosophy of how ICU liberation serves patients and families. Crit Care Med 2017; 45 (02) 321-330
  • 9 Girard TD, Alhazzani W, Kress JP. et al; ATS/CHEST Ad Hoc Committee on Liberation from Mechanical Ventilation in Adults. An Official American Thoracic Society/American College of Chest Physicians Clinical Practice Guideline: liberation from mechanical ventilation in critically ill adults. Rehabilitation protocols, ventilator liberation protocols, and cuff leak tests. Am J Respir Crit Care Med 2017; 195 (01) 120-133
  • 10 Riker RR, Shehabi Y, Bokesch PM. et al; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA 2009; 301 (05) 489-499
  • 11 Jakob SM, Ruokonen E, Grounds RM. et al; Dexmedetomidine for Long-Term Sedation Investigators. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA 2012; 307 (11) 1151-1160
  • 12 Shehabi Y, Bellomo R, Kadiman S. et al; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Sedation intensity in the first 48 hours of mechanical ventilation and 180-day mortality: a multinational prospective longitudinal cohort study. Crit Care Med 2018; 46 (06) 850-859
  • 13 Gélinas C, Fillion L, Puntillo KA, Viens C, Fortier M. Validation of the critical-care pain observation tool in adult patients. Am J Crit Care 2006; 15 (04) 420-427
  • 14 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 (10) 1338-1344
  • 15 Ahlers SJ, van der Veen AM, van Dijk M, Tibboel D, Knibbe CA. The use of the Behavioral Pain Scale to assess pain in conscious sedated patients. Anesth Analg 2010; 110 (01) 127-133
  • 16 Balzer F, Weiß B, Kumpf O. et al. Early deep sedation is associated with decreased in-hospital and two-year follow-up survival. Crit Care 2015; 19: 197
  • 17 Shehabi Y, Bellomo R, Reade MC. et al; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators, ANZICS Clinical Trials Group. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med 2012; 186 (08) 724-731
  • 18 Matthay MA, Aldrich JM, Gotts JE. Treatment for severe acute respiratory distress syndrome from COVID-19. Lancet Respir Med 2020; 8 (05) 433-434
  • 19 Zhou F, Yu T, Du R. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395 (10229): 1054-1062
  • 20 Wunsch H. Mechanical ventilation in COVID-19: interpreting the current epidemiology. Am J Respir Crit Care Med 2020; 202 (01) 1-4
  • 21 Gattinoni L, Chiumello D, Caironi P. et al. COVID-19 pneumonia: different respiratory treatments for different phenotypes?. Intensive Care Med 2020; 46 (06) 1099-1102
  • 22 Hutchison LC, O'Brien CE. Changes in pharmacokinetics and pharmacodynamics in the elderly patient. J Pharm Pract 2007; 20: 4-12
  • 23 Mangoni AA, Jackson SH. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol 2004; 57 (01) 6-14
  • 24 Lee SJ, Lindquist K, Segal MR, Covinsky KE. Development and validation of a prognostic index for 4-year mortality in older adults. JAMA 2006; 295 (07) 801-808
  • 25 Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and consequences of ICU delirium. Intensive Care Med 2007; 33 (01) 66-73
  • 26 Shehabi Y, Howe BD, Bellomo R. et al; ANZICS Clinical Trials Group and the SPICE III Investigators. Early sedation with dexmedetomidine in critically ill patients. N Engl J Med 2019; 380 (26) 2506-2517
  • 27 Zaal IJ, Devlin JW, Peelen LM, Slooter AJ. A systematic review of risk factors for delirium in the ICU. Crit Care Med 2015; 43 (01) 40-47
  • 28 Park HJ, Moon DE. Pharmacologic management of chronic pain. Korean J Pain 2010; 23 (02) 99-108
  • 29 Vissers KC, Besse K, Hans G, Devulder J, Morlion B. Opioid rotation in the management of chronic pain: where is the evidence?. Pain Pract 2010; 10 (02) 85-93
  • 30 Philips BJ, Lane K, Dixon J, Macphee I. The effects of acute renal failure on drug metabolism. Expert Opin Drug Metab Toxicol 2014; 10 (01) 11-23
  • 31 Darrouj J, Karma L, Arora R. Cardiovascular manifestations of sedatives and analgesics in the critical care unit. Am J Ther 2009; 16 (04) 339-353
  • 32 Schenone AL, Chen K, Andress K, Militello M, Cho L. Editor's choice- sedation in the coronary intensive care unit: an adapted algorithm for critically ill cardiovascular patient. Eur Heart J Acute Cardiovasc Care 2019; 8 (02) 167-175
  • 33 Morelli A, Sanfilippo F, Arnemann P. et al. The effect of propofol and dexmedetomidine sedation on norepinephrine requirements in septic shock patients: a crossover trial. Crit Care Med 2019; 47 (02) e89-e95
  • 34 Liu H, Ji F, Peng K, Applegate II RL, Fleming N. Sedation after cardiac surgery: is one drug better than another?. Anesth Analg 2017; 124 (04) 1061-1070
  • 35 Oddo M, Crippa IA, Mehta S. et al. Optimizing sedation in patients with acute brain injury. Crit Care 2016; 20 (01) 128
  • 36 Paul M, Bougouin W, Dumas F. et al. Comparison of two sedation regimens during targeted temperature management after cardiac arrest. Resuscitation 2018; 128: 204-210
  • 37 Piquilloud L, Vignaux L, Bialais E. et al. Neurally adjusted ventilatory assist improves patient-ventilator interaction. Intensive Care Med 2011; 37 (02) 263-271
  • 38 Conti G, Ranieri VM, Costa R. et al. Effects of dexmedetomidine and propofol on patient-ventilator interaction in difficult-to-wean, mechanically ventilated patients: a prospective, open-label, randomised, multicentre study. Crit Care 2016; 20 (01) 206
  • 39 Devlin JW, Roberts RJ, Fong JJ. et al. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med 2010; 38 (02) 419-427
  • 40 Reade MC, Eastwood GM, Bellomo R. et al; DahLIA Investigators, Australian and New Zealand Intensive Care Society Clinical Trials Group. Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium: a randomized clinical trial. JAMA 2016; 315 (14) 1460-1468
  • 41 Capell EL, Tipping CJ, Hodgson CL. Barriers to implementing expert safety recommendations for early mobilisation in intensive care unit during mechanical ventilation: a prospective observational study. Aust Crit Care 2019; 32 (03) 185-190
  • 42 Mehta S, Burry L, Cook D. et al; SLEAP Investigators, Canadian Critical Care Trials Group. Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA 2012; 308 (19) 1985-1992
  • 43 Group ST. SRLF Trial Group. Impact of oversedation prevention in ventilated critically ill patients: a randomized trial-the AWARE study. Ann Intensive Care 2018; 8 (01) 93
  • 44 Olsen HT, Nedergaard HK, Strøm T. et al. Nonsedation or light sedation in critically ill, mechanically ventilated patients. N Engl J Med 2020; 382 (12) 1103-1111
  • 45 Aitken LM, Bucknall T, Kent B, Mitchell M, Burmeister E, Keogh SJ. Protocol-directed sedation versus non-protocol-directed sedation in mechanically ventilated intensive care adults and children. Cochrane Database Syst Rev 2018; 11: CD009771
  • 46 Pandharipande P, Banerjee A, McGrane S, Ely EW. Liberation and animation for ventilated ICU patients: the ABCDE bundle for the back-end of critical care. Crit Care 2010; 14 (03) 157
  • 47 Schelling G, Stoll C, Haller M. et al. Health-related quality of life and posttraumatic stress disorder in survivors of the acute respiratory distress syndrome. Crit Care Med 1998; 26 (04) 651-659
  • 48 Chanques G, Viel E, Constantin J-M. et al. The measurement of pain in intensive care unit: comparison of 5 self-report intensity scales. Pain 2010; 151 (03) 711-721
  • 49 Gélinas C, Johnston C. Pain assessment in the critically ill ventilated adult: validation of the Critical-Care Pain Observation Tool and physiologic indicators. Clin J Pain 2007; 23 (06) 497-505
  • 50 Devlin JW, Roberts RJ. Pharmacology of commonly used analgesics and sedatives in the ICU: benzodiazepines, propofol, and opioids. Crit Care Clin 2009; 25 (03) 431-449 , vii
  • 51 Muellejans B, López A, Cross MH, Bonome C, Morrison L, Kirkham AJ. Remifentanil versus fentanyl for analgesia based sedation to provide patient comfort in the intensive care unit: a randomized, double-blind controlled trial [ISRCTN43755713]. Crit Care 2004; 8 (01) R1-R11
  • 52 Devlin JW. The pharmacology of oversedation in mechanically ventilated adults. Curr Opin Crit Care 2008; 14 (04) 403-407
  • 53 Allouche S, Noble F, Marie N. Opioid receptor desensitization: mechanisms and its link to tolerance. Front Pharmacol 2014; 5: 280
  • 54 Yu EH, Tran DH, Lam SW, Irwin MG. Remifentanil tolerance and hyperalgesia: short-term gain, long-term pain?. Anaesthesia 2016; 71 (11) 1347-1362
  • 55 Vargas-Schaffer G. Is the WHO analgesic ladder still valid? Twenty-four years of experience. Can Fam Physician 2010; 56 (06) 514-517 , e202–e205
  • 56 Perbet S, Verdonk F, Godet T. et al. Low doses of ketamine reduce delirium but not opiate consumption in mechanically ventilated and sedated ICU patients: a randomised double-blind control trial. Anaesth Crit Care Pain Med 2018; 37 (06) 589-595
  • 57 Sharma C, Mehta V. Paracetamol: mechanisms and updates. Contin Educ Anaesth Crit Care Pain 2013; 1-6
  • 58 Maund E, McDaid C, Rice S, Wright K, Jenkins B, Woolacott N. Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs for the reduction in morphine-related side-effects after major surgery: a systematic review. Br J Anaesth 2011; 106 (03) 292-297
  • 59 Subramaniam B, Shankar P, Shaefi S. et al. Effect of intravenous acetaminophen vs placebo combined with propofol or dexmedetomidine on postoperative delirium among older patients following cardiac surgery: the DEXACET randomized clinical trial. JAMA 2019; 321 (07) 686-696
  • 60 Laskowski K, Stirling A, McKay WP, Lim HJ. A systematic review of intravenous ketamine for postoperative analgesia. Can J Anaesth 2011; 58 (10) 911-923
  • 61 De Pinto M, Jelacic J, Edwards WT. Very-low-dose ketamine for the management of pain and sedation in the ICU. J Opioid Manag 2008; 4 (01) 54-56
  • 62 Shehabi Y, Grant P, Wolfenden H. et al. Prevalence of delirium with dexmedetomidine compared with morphine based therapy after cardiac surgery: a randomized controlled trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study). Anesthesiology 2009; 111 (05) 1075-1084
  • 63 Zhao L-H, Shi Z-H, Chen G-Q. et al. Use of dexmedetomidine for prophylactic analgesia and sedation in patients with delayed extubation after craniotomy: a randomized controlled trial. J Neurosurg Anesthesiol 2017; 29 (02) 132-139
  • 64 Pesonen A, Suojaranta-Ylinen R, Hammarén E. et al. Pregabalin has an opioid-sparing effect in elderly patients after cardiac surgery: a randomized placebo-controlled trial. Br J Anaesth 2011; 106 (06) 873-881
  • 65 Pandey CK, Bose N, Garg G. et al. Gabapentin for the treatment of pain in guillain-barré syndrome: a double-blinded, placebo-controlled, crossover study. Anesth Analg 2002; 95 (06) 1719-1723
  • 66 Chou R, Gordon DB, de Leon-Casasola OA. et al. Management of Postoperative Pain: a clinical practice guideline from the American pain society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' committee on regional anesthesia, executive committee, and administrative council. J Pain 2016; 17 (02) 131-157
  • 67 Sessler CN, Riker RR, Ramsay MA. Evaluating and monitoring sedation, arousal, and agitation in the ICU. Semin Respir Crit Care Med 2013; 34 (02) 169-178
  • 68 Richards-Belle A, Canter RR, Power GS. et al. National survey and point prevalence study of sedation practice in UK critical care. Crit Care 2016; 20 (01) 355
  • 69 Holtkamp M. Pharmacotherapy for refractory and super-refractory status epilepticus in adults. Drugs 2018; 78 (03) 307-326
  • 70 Schmidt KJ, Doshi MR, Holzhausen JM, Natavio A, Cadiz M, Winegardner JE. Treatment of severe alcohol withdrawal. Ann Pharmacother 2016; 50 (05) 389-401
  • 71 Hemphill S, McMenamin L, Bellamy MC, Hopkins PM. Propofol infusion syndrome: a structured literature review and analysis of published case reports. Br J Anaesth 2019; 122 (04) 448-459
  • 72 Bauer TM, Ritz R, Haberthür C. et al. Prolonged sedation due to accumulation of conjugated metabolites of midazolam. Lancet 1995; 346 (8968): 145-147
  • 73 Kok L, Slooter AJ, Hillegers MH, van Dijk D, Veldhuijzen DS. Benzodiazepine use and neuropsychiatric outcomes in the ICU: a systematic review. Crit Care Med 2018; 46 (10) 1673-1680
  • 74 Fraser GL, Devlin JW, Worby CP. et al. Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials. Crit Care Med 2013; 41 (09) (Suppl. 01) S30-S38
  • 75 Weerink MAS, Struys MMRF, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine. Clin Pharmacokinet 2017; 56 (08) 893-913
  • 76 Cioccari L, Luethi N, Bailey M. et al; ANZICS Clinical Trials Group and the SPICE III Investigators. The effect of dexmedetomidine on vasopressor requirements in patients with septic shock: a subgroup analysis of the Sedation Practice in Intensive Care Evaluation [SPICE III] trial. Crit Care 2020; 24 (01) 441
  • 77 Wang G, Niu J, Li Z, Lv H, Cai H. The efficacy and safety of dexmedetomidine in cardiac surgery patients: A systematic review and meta-analysis. PLoS One 2018; 13 (09) e0202620
  • 78 Skrobik Y, Duprey MS, Hill NS, Devlin JW. Low-dose nocturnal dexmedetomidine prevents ICU delirium. a randomized, placebo-controlled trial. Am J Respir Crit Care Med 2018; 197 (09) 1147-1156
  • 79 Schrijver EJ, de Graaf K, de Vries OJ, Maier AB, Nanayakkara PW. Efficacy and safety of haloperidol for in-hospital delirium prevention and treatment: A systematic review of current evidence. Eur J Intern Med 2016; 27: 14-23
  • 80 van den Boogaard M, Slooter AJC, Brüggemann RJM. et al; REDUCE Study Investigators. Effect of haloperidol on survival among critically ill adults with a high risk of delirium: the REDUCE randomized clinical trial. JAMA 2018; 319 (07) 680-690
  • 81 Girard TD, Exline MC, Carson SS. et al; MIND-USA Investigators. Haloperidol and ziprasidone for treatment of delirium in critical illness. N Engl J Med 2018; 379 (26) 2506-2516
  • 82 Burry L, Hutton B, Williamson DR. et al. Pharmacological interventions for the treatment of delirium in critically ill adults. Cochrane Database Syst Rev 2019; 9: CD011749
  • 83 Dube KM, DeGrado J, Hohlfelder B, Szumita PM. Evaluation of the effects of quetiapine on QTc prolongation in critically ill patients. J Pharm Pract 2018; 31 (03) 292-297
  • 84 Erstad BL, Barletta JF. Drug dosing in the critically ill obese patient-a focus on sedation, analgesia, and delirium. Crit Care 2020; 24 (01) 315
  • 85 Pollock W, Rose L, Dennis CL. Pregnant and postpartum admissions to the intensive care unit: a systematic review. Intensive Care Med 2010; 36 (09) 1465-1474
  • 86 Gaffney A. Critical care in pregnancy: is it different?. Semin Perinatol 2014; 38 (06) 329-340
  • 87 Wikner BN, Stiller CO, Källén B, Asker C. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: maternal characteristics. Pharmacoepidemiol Drug Saf 2007; 16 (09) 988-994
  • 88 Esmaoglu A, Ulgey A, Akin A, Boyaci A. Comparison between dexmedetomidine and midazolam for sedation of eclampsia patients in the intensive care unit. J Crit Care 2009; 24 (04) 551-555
  • 89 Rashid MR, Najeeb R, Mushtaq S, Habib R. Comparative evaluation of midazolam, dexmedetomidine, and propofol as intensive care unit sedatives in postoperative electively ventilated eclamptic patients. J Anaesthesiol Clin Pharmacol 2017; 33 (03) 331-336
  • 90 Duan M, Lee J, Bittner EA. Dexmedetomidine for sedation in the parturient with respiratory failure requiring noninvasive ventilation. Respir Care 2012; 57 (11) 1967-1969
  • 91 MacMurdo MP. H. A preganant pause: the use of dexmedetomidine for agitated delirium in pregnancy. Crit Care Med 2016; 44: 539