Non-opioid Pain/Sedation Management in the ICU

There’s a lecture that I have shared with audiences looking at opioid-sparing medications for pain and sedation in the intensive care unit that I have been working on for several years. In this post, I will be sharing this content with you all with the citations you everyone can better their practices and we can provide better care for our patients. This post will be a living, breathing one-stop-shop so we can all get better at pain management in the ICU together. Last updated 03/03/22.

The reason why attempting to spare opioids in the pain management of the patients in the ICU is to potentially diminish the likelihood that people are going to develop an addiction. Wunsch et al. looked at over 25,000 patients who were opioid naive. 2.6% of those patients remained on opioids a year out from their discharge. 1.2% of patients on the vent in the MICU and 4.0% of patients on the vent in SICU remained on opioids a year out. That may not seem like that much at face value, but think of all the patients we care for.

Barnett stated in NEJM that “a single opioid prescription in the emergency department, after surgery, or at the dentist’s office, 1% to 6% end up using opioids for at least 12 months or being diagnosed with opioid use disorder.”

Barnett ML. Opioid Prescribing in the Midst of Crisis – Myths and Realities. N Engl J Med. 2020 Mar 19;382(12):1086-1088. doi: 10.1056/NEJMp1914257. PMID: 32187467.
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Table of Contents

  • Ketamine
  • Magnesium
  • Lidocaine
  • Gabapentin/Pregabalin
  • Dexmedetomidine
  • NSAIDs
  • Acetaminophen
  • Regional Anesthesia

Ketamine for Pain Management in the ICU

Amer M, Maghrabi K, Bawazeer M, Alshaikh K, Shaban M, Rizwan M, Amin R, De Vol E, Baali M, Altewerki M, Bano M, Alkhaldi F, Alenazi S, Hijazi M. Adjunctive ketamine for sedation in critically ill mechanically ventilated patients: an active-controlled, pilot, feasibility clinical trial. J Intensive Care. 2021 Aug 30;9(1):54. doi: 10.1186/s40560-021-00569-1. PMID: 34462007; PMCID: PMC8404029.
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I discussed being careful with potential complications of ketamine in patients who have catecholamine-dependent heart failure HERE.

Ketamine for delayed sequence intubation HERE.

Manasco AT, Stephens RJ, Yaeger LH, Roberts BW, Fuller BM. Ketamine sedation in mechanically ventilated patients: A systematic review and meta-analysis. J Crit Care. 2020 Apr;56:80-88. doi: 10.1016/j.jcrc.2019.12.004. Epub 2019 Dec 9. PMID: 31865256.
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Lidocaine

Continuous Infusions of lidocaine was discussed in this post.

Gabapentin/Pregabalin

Pregabalin in the cardiac surgery population? Click here.

Citations

Wunsch H, Hill AD, Fu L, Fowler RA, Wang HT, Gomes T, Fan E, Juurlink DN, Pinto R, Wijeysundera DN, Scales DC. New Opioid Use after Invasive Mechanical Ventilation and Hospital Discharge. Am J Respir Crit Care Med. 2020 Aug 15;202(4):568-575. doi: 10.1164/rccm.201912-2503OC. PMID: 32348694; PMCID: PMC7427379.
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Erstad BL. Attempts to Limit Opioid Prescribing in Critically Ill Patients: Not So Easy, Not So Fast. Ann Pharmacother. 2019 Jul;53(7):716-725. doi: 10.1177/1060028018824724. Epub 2019 Jan 13. PMID: 30638027.
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Puntillo KA, Max A, Timsit JF, Vignoud L, Chanques G, Robleda G, Roche-Campo F, Mancebo J, Divatia JV, Soares M, Ionescu DC, Grintescu IM, Vasiliu IL, Maggiore SM, Rusinova K, Owczuk R, Egerod I, Papathanassoglou ED, Kyranou M, Joynt GM, Burghi G, Freebairn RC, Ho KM, Kaarlola A, Gerritsen RT, Kesecioglu J, Sulaj MM, Norrenberg M, Benoit DD, Seha MS, Hennein A, Periera FJ, Benbenishty JS, Abroug F, Aquilina A, Monte JR, An Y, Azoulay E. Determinants of procedural pain intensity in the intensive care unit. The Europain® study. Am J Respir Crit Care Med. 2014 Jan 1;189(1):39-47. doi: 10.1164/rccm.201306-1174OC. PMID: 24262016. 
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Sessler CN, Grap MJ, Brophy GM. Multidisciplinary management of sedation and analgesia in critical care. Semin Respir Crit Care Med. 2001;22(2):211-26. doi: 10.1055/s-2001-13834. PMID: 16088675.
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Ketamine Citations

Hirota K, Lambert DG. Ketamine: its mechanism(s) of action and unusual clinical uses. Br J Anaesth. 1996 Oct;77(4):441-4. doi: 10.1093/bja/77.4.441. PMID: 8942324.
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GuilGuillou N, Tanguy M, Seguin P, Branger B, Campion JP, Mallédant Y. The effects of small-dose ketamine on morphine consumption in surgical intensive care unit patients after major abdominal surgery. Anesth Analg. 2003 Sep;97(3):843-847. doi: 10.1213/01.ANE.0000075837.67275.36. PMID: 12933413.  
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Jennings PA, Cameron P, Bernard S, Walker T, Jolley D, Fitzgerald M, Masci K. Morphine and ketamine is superior to morphine alone for out-of-hospital trauma analgesia: a randomized controlled trial. Ann Emerg Med. 2012 Jun;59(6):497-503. doi: 10.1016/j.annemergmed.2011.11.012. Epub 2012 Jan 13. PMID: 22243959. 
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Walters MK, Farhat J, Bischoff J, Foss M, Evans C. Ketamine as an Analgesic Adjuvant in Adult Trauma Intensive Care Unit Patients With Rib Fracture. Ann Pharmacother. 2018 Sep;52(9):849-854. doi: 10.1177/1060028018768451. Epub 2018 Apr 2. PMID: 29607659.
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Jabre P, Combes X, Lapostolle F, Dhaouadi M, Ricard-Hibon A, Vivien B, Bertrand L, Beltramini A, Gamand P, Albizzati S, Perdrizet D, Lebail G, Chollet-Xemard C, Maxime V, Brun-Buisson C, Lefrant JY, Bollaert PE, Megarbane B, Ricard JD, Anguel N, Vicaut E, Adnet F; KETASED Collaborative Study Group. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009 Jul 25;374(9686):293-300. doi: 10.1016/S0140-6736(09)60949-1. Epub 2009 Jul 1. PMID: 19573904.
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Merelman AH, Perlmutter MC, Strayer RJ. Alternatives to Rapid Sequence Intubation: Contemporary Airway Management with Ketamine. West J Emerg Med. 2019 May;20(3):466-471. doi: 10.5811/westjem.2019.4.42753. Epub 2019 Apr 26. PMID: 31123547; PMCID: PMC6526883.
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Garber PM, Droege CA, Carter KE, Harger NJ, Mueller EW. Continuous Infusion Ketamine for Adjunctive Analgosedation in Mechanically Ventilated, Critically Ill Patients. Pharmacotherapy. 2019 Mar;39(3):288-296. doi: 10.1002/phar.2223. PMID: 30746728.
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Bovill JG. Intravenous anesthesia for the patient with left ventricular dysfunction. Semin Cardiothorac Vasc Anesth. 2006 Mar;10(1):43-8. doi: 10.1177/108925320601000108. PMID: 16703233.
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Patanwala AE, Martin JR, Erstad BL. Ketamine for Analgosedation in the Intensive Care Unit: A Systematic Review. J Intensive Care Med. 2017 Jul;32(6):387-395. doi: 10.1177/0885066615620592. Epub 2015 Dec 8. PMID: 26647407.
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Umunna BP, Tekwani K, Barounis D, Kettaneh N, Kulstad E. Ketamine for continuous sedation of mechanically ventilated patients. J Emerg Trauma Shock. 2015 Jan-Mar;8(1):11-5. doi: 10.4103/0974-2700.145414. PMID: 25709246; PMCID: PMC4335149. 
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Buchheit JL, Yeh DD, Eikermann M, Lin H. Impact of Low-Dose Ketamine on the Usage of Continuous Opioid Infusion for the Treatment of Pain in Adult Mechanically Ventilated Patients in Surgical Intensive Care Units. J Intensive Care Med. 2019 Aug;34(8):646-651. doi: 10.1177/0885066617706907. Epub 2017 May 3. PMID: 28468568.
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Pruskowski KA, Harbourt K, Pajoumand M, Chui SJ, Reynolds HN. Impact of Ketamine Use on Adjunctive Analgesic and Sedative Medications in Critically Ill Trauma Patients. Pharmacotherapy. 2017 Dec;37(12):1537-1544. doi: 10.1002/phar.2042. Epub 2017 Nov 29. PMID: 29023898.
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Christ G, Mundigler G, Merhaut C, Zehetgruber M, Kratochwill C, Heinz G, Siostrzonek P. Adverse cardiovascular effects of ketamine infusion in patients with catecholamine-dependent heart failure. Anaesth Intensive Care. 1997 Jun;25(3):255-9. doi: 10.1177/0310057X9702500308. PMID: 9209606.
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Strumpher J, Jacobsohn E. Pulmonary hypertension and right ventricular dysfunction: physiology and perioperative management. J Cardiothorac Vasc Anesth. 2011 Aug;25(4):687-704. doi: 10.1053/j.jvca.2011.02.022. Epub 2011 May 26. PMID: 21620732.  
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Amer M, Maghrabi K, Bawazeer M, Alshaikh K, Shaban M, Rizwan M, Amin R, De Vol E, Baali M, Altewerki M, Bano M, Alkhaldi F, Alenazi S, Hijazi M. Adjunctive ketamine for sedation in critically ill mechanically ventilated patients: an active-controlled, pilot, feasibility clinical trial. J Intensive Care. 2021 Aug 30;9(1):54. doi: 10.1186/s40560-021-00569-1. PMID: 34462007; PMCID: PMC8404029.
Link to Article
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Magnesium Citations

Altun D, Eren G, Cetingok H, Hergünsel GO, Çukurova Z. Can we use magnesium for sedation in the intensive care unit for critically ill patients: Is it as effective as other sedatives? Agri. 2019 Apr;31(2):86-92. English. doi: 10.14744/agri.2019.59244. PMID: 30995329.
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Lidocaine Citations

Kranke P, Jokinen J, Pace NL, Schnabel A, Hollmann MW, Hahnenkamp K, Eberhart LH, Poepping DM, Weibel S. Continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery. Cochrane Database Syst Rev. 2015 Jul 16;(7):CD009642. doi: 10.1002/14651858.CD009642.pub2. Update in: Cochrane Database Syst Rev. 2018 Jun 04;6:CD009642. PMID: 26184397.
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Mo Y, Thomas MC, Antigua AD, Ebied AM, Karras GE Jr. Continuous Lidocaine Infusion as Adjunctive Analgesia in Intensive Care Unit Patients. J Clin Pharmacol. 2017 Jul;57(7):830-836. doi: 10.1002/jcph.874. Epub 2017 Feb 7. PMID: 28168730; PMCID: PMC5471129.  
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Masic D, Liang E, Long C, Sterk EJ, Barbas B, Rech MA. Intravenous Lidocaine for Acute Pain: A Systematic Review. Pharmacotherapy. 2018 Dec;38(12):1250-1259. doi: 10.1002/phar.2189. Epub 2018 Nov 9. PMID: 30303542.
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Weibel S, Jelting Y, Pace NL, Helf A, Eberhart LH, Hahnenkamp K, Hollmann MW, Poepping DM, Schnabel A, Kranke P. Continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery in adults. Cochrane Database Syst Rev. 2018 Jun 4;6(6):CD009642. doi: 10.1002/14651858.CD009642.pub3. PMID: 29864216; PMCID: PMC6513586.
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Dunn LK, Durieux ME. Perioperative Use of Intravenous Lidocaine. Anesthesiology. 2017 Apr;126(4):729-737. doi: 10.1097/ALN.0000000000001527. PMID: 28114177. 
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Gabapentin & Pregabalin Citations

Pandey CK, Raza M, Tripathi M, Navkar DV, Kumar A, Singh UK. The comparative evaluation of gabapentin and carbamazepine for pain management in Guillain-Barré syndrome patients in the intensive care unit. Anesth Analg. 2005 Jul;101(1):220-5, table of contents. doi: 10.1213/01.ANE.0000152186.89020.36. PMID: 15976235.
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Borde DP, Futane SS, Asegaonkar B, Apsingekar P, Khade S, Khodve B, Puranik M, George A, Joshi S. Effect of Perioperative Pregabalin on Postoperative Quality of Recovery in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting (OPCABG): A Prospective, Randomized, Double-Blind Trial. J Cardiothorac Vasc Anesth. 2017 Aug;31(4):1241-1245. doi: 10.1053/j.jvca.2016.09.029. Epub 2016 Sep 28. PMID: 27939574.  
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Joshi SS, Jagadeesh AM. Efficacy of perioperative pregabalin in acute and chronic post-operative pain after off-pump coronary artery bypass surgery: a randomized, double-blind placebo controlled trial. Ann Card Anaesth. 2013 Jul-Sep;16(3):180-5. doi: 10.4103/0971-9784.114239. PMID: 23816671.
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Pesonen A, Suojaranta-Ylinen R, Hammarén E, Kontinen VK, Raivio P, Tarkkila P, Rosenberg PH. Pregabalin has an opioid-sparing effect in elderly patients after cardiac surgery: a randomized placebo-controlled trial. Br J Anaesth. 2011 Jun;106(6):873-81. doi: 10.1093/bja/aer083. Epub 2011 Apr 6. PMID: 21474474.
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Schmidt PC, Ruchelli G, Mackey SC, Carroll IR. Perioperative gabapentinoids: choice of agent, dose, timing, and effects on chronic postsurgical pain. Anesthesiology. 2013 Nov;119(5):1215-21. doi: 10.1097/ALN.0b013e3182a9a896. PMID: 24051389.
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Dexmedetomidine Citations

Tang C, Xia Z. Dexmedetomidine in perioperative acute pain management: a non-opioid adjuvant analgesic. J Pain Res. 2017 Aug 11;10:1899-1904. doi: 10.2147/JPR.S139387. PMID: 28860845; PMCID: PMC5565238.
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Shehabi Y, Grant P, Wolfenden H, Hammond N, Bass F, Campbell M, Chen J. 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 Nov;111(5):1075-84. doi: 10.1097/ALN.0b013e3181b6a783. PMID: 19786862.
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Martin E, Ramsay G, Mantz J, Sum-Ping ST. The role of the alpha2-adrenoceptor agonist dexmedetomidine in postsurgical sedation in the intensive care unit. J Intensive Care Med. 2003 Jan-Feb;18(1):29-41. doi: 10.1177/0885066602239122. PMID: 15189665.
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Shehabi Y, Howe BD, Bellomo R, Arabi YM, Bailey M, Bass FE, Bin Kadiman S, McArthur CJ, Murray L, Reade MC, Seppelt IM, Takala J, Wise MP, Webb SA; ANZICS Clinical Trials Group and the SPICE III Investigators. Early Sedation with Dexmedetomidine in Critically Ill Patients. N Engl J Med. 2019 Jun 27;380(26):2506-2517. doi: 10.1056/NEJMoa1904710. Epub 2019 May 19. PMID: 31112380.
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Zhang T, Mei Q, Dai S, Liu Y, Zhu H. Use of dexmedetomidine in patients with sepsis: a systematic review and meta-analysis of randomized-controlled trials. Ann Intensive Care. 2022 Aug 27;12(1):81. doi: 10.1186/s13613-022-01052-2. PMID: 36029410.
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NSAID Citations

Motov S, Yasavolian M, Likourezos A, Pushkar I, Hossain R, Drapkin J, Cohen V, Filk N, Smith A, Huang F, Rockoff B, Homel P, Fromm C. Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med. 2017 Aug;70(2):177-184. doi: 10.1016/j.annemergmed.2016.10.014. Epub 2016 Dec 16. PMID: 27993418.
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IV Acetaminophen Citations

Douzjian DJ, Kulik A. Old Drug, New Route: A Systematic Review of Intravenous Acetaminophen After Adult Cardiac Surgery. J Cardiothorac Vasc Anesth. 2017 Apr;31(2):694-701. doi: 10.1053/j.jvca.2016.03.134. Epub 2016 Mar 16. PMID: 27498260.
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Mahshidfar B, Sameti A, Abbasi S, Farsi D, Mofidi M, Hafezimoghadam P, Rahimzadeh P, Rezai M. Can intravenous acetaminophen reduce the needs to more opioids to control pain in intubated patients? Indian J Crit Care Med. 2016 Aug;20(8):465-8. doi: 10.4103/0972-5229.188197. PMID: 27630458; PMCID: PMC4994126.
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Jibril F, Sharaby S, Mohamed A, Wilby KJ. Intravenous versus Oral Acetaminophen for Pain: Systematic Review of Current Evidence to Support Clinical Decision-Making. Can J Hosp Pharm. 2015 May-Jun;68(3):238-47. doi: 10.4212/cjhp.v68i3.1458. PMID: 26157186; PMCID: PMC4485512.
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Wasserman I, Poeran J, Zubizarreta N, Babby J, Serban S, Goldberg AT, Greenstein AJ, Memtsoudis SG, Mazumdar M, Leibowitz AB. Impact of Intravenous Acetaminophen on Perioperative Opioid Utilization and Outcomes in Open Colectomies: A Claims Database Analysis. Anesthesiology. 2018 Jul;129(1):77-88. doi: 10.1097/ALN.0000000000002227. PMID: 29677001.
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Altun D, Çınar Ö, Özker E, Türköz A. The effect of tramadol plus paracetamol on consumption of morphine after coronary artery bypass grafting. J Clin Anesth. 2017 Feb;36:189-193. doi: 10.1016/j.jclinane.2016.10.030. Epub 2016 Dec 5. PMID: 28183564.
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Regional Anesthesia Citations

Capdevila M, Ramin S, Capdevila X. Regional anesthesia and analgesia after surgery in ICU. Curr Opin Crit Care. 2017 Oct;23(5):430-439. doi: 10.1097/MCC.0000000000000440. PMID: 28820799.
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Rubio-Haro R, Morales-Sarabia J, Ferrer-Gomez C, de Andres J. Regional analgesia techniques for pain management in patients admitted to the intensive care unit. Minerva Anestesiol. 2019 Oct;85(10):1118-1128. doi: 10.23736/S0375-9393.19.13447-5. Epub 2019 Apr 2. PMID: 30945513.
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