Introduction   This is the second of a three-part series. Fast Fact #33 reviewed a protocol for removing the ventilator, and Fast Fact #35 will review information for families. 

The most common symptoms related to ventilator withdrawal are breathlessness, excessive oral secretions, and anxiety.  Opioids and benzodiazepines are the primary medications used; concerns about unintended hastened death are exaggerated, particularly if established dosing guidelines are followed (see Fast Fact #8).  There is no medical or ethical justification for withholding comfort medications when death following ventilator withdrawal is the expected outcome.  However, increasing doses beyond the levels needed to achieve comfort/sedation, with the intention of hastening death, is euthanasia and is not acceptable/legal medical practice.  

Research suggests that opioids and benzodiazepines do not shorten survival but do help minimize respiratory distress in terminal extubations.  Therefore, pre-bolus doses should be considered even for those who are comatose. The doses needed to control symptoms depend on the neurological status of the patient and presence of drug tolerance (these same drugs are commonly used in routine ICU care). In all cases, an experienced clinician should remain at the bedside prior to and immediately following extubation until adequate symptom control is assured. Collaborate with your pharmacist prior to the planned procedure when formulating your care plan.  

Medication protocol 

1. Stop all paralytics (e.g., succinylcholine, vecuronium). Besides ensuring a patient cannot breathe, they do not prevent or treat any discomfort and in fact may add to discomfort by preventing patients from communicating or demonstrating distress. When patients have multi-organ failure, some paralytics may not be cleared for 2-18 hours. Therefore, if there is doubt as to whether the paralytics have worn off, utilize a peripheral nerve stimulator.  It is ok to extubate when you see muscle twitches with 4 consecutive nerve stimulations.
2. Administer glycopyrrolate 0.4 mg IV 20-30 minutes prior to extubation to minimize secretions.
3. Administer an IV bolus dose of an opioid (i.e. morphine 2-10 mg IV) and a benzodiazepine (e.g., lorazepam 1-2 mg IV) if anxiety is anticipated 20-30 minutes prior to the extubation. Consider an IV continuous infusion of sedating medication (see below).  Do not rely on subcutaneous or enteral drug administration as these take longer to work.  For children, obtain dosing advice from a pharmacist or pediatric intensivist.
4. Titrate medications to control labored respirations and achieve the desired state of sedation prior to extubation. Testing the eyelid reflex (does the patient blink from tactile corneal stimulation) is a common method of quickly assessing level of consciousness.
5. Have additional medication drawn up and ready to administer at the bedside if needed.
6. After ventilator withdrawal: most respiratory distress ensues in the first few hours after the extubation. If distress is noted, utilize additional bolus doses of opioids and benzodiazepines (e.g. morphine 5-10 mg IV push q 10 min, and/or midazolam, 2-4 mg IV push q 10 min, until distress is relieved). You can adjust infusion rates to maintain relief but remember they will have a delayed effect. Therefore, rely more on bolus medications and less on infusion rates to control distress seen after the extubation.
7. Specific dosages are less important than the goal of symptom relief. A goal should be to keep the respiratory rate < 30 and eliminate grimacing, agitation, and labored respirations. The respiratory distress observational scale can be a useful tool for nurses to determine if additional as needed opioid administration is appropriate.
8. Orders such as “morphine drip 1-20 mg/hr, titrate as needed” are inappropriate as they will likely mismanage the acute symptom distress and place undue burden on the bedside nurse to make clinical management decisions. 

NOTE: The following regimens are commonly used; all require a bolus dose commonly followed by a continuous infusion.  Dose ranges are approximations and depend in part on patients’ prior exposure to opioids and benzodiazepines.  Clinicians should use clinical judgment when deciding on what specific drugs and doses to use.  Institutions should have policy and clinical guidelines about the use of opioids and sedatives in these circumstances and utilize quality improvement processes to ensure they are providing the best care.  Clinicians unfamiliar with the use of these agents in the setting of ventilator withdrawal are urged to consult with an anesthesiologist, critical care specialist, pharmacist, or palliative specialist prior to use.

Regimen A:  Morphine plus Midazolam (Adult doses) Good for patients with limited consciousness and/or little prior exposure to these drugs (and thus less risk of tolerance). 

Bolus:    Morphine 2-10 mg; Midazolam 1-2 mg
Infusion: Morphine 50% of the bolus dose in mg/hr; Midazolam 1 mg/hr 

Regimen B:   Pentobarbital (Adult doses) Good for the awake patient who can be expected to have respiratory distress following ventilator withdrawal.   

Bolus:    1-2 mg/kg (at rate of 50 mg/min)
Infusion: 1-2 mg/kg/hr 

Regimen C:  Propofol (Adult doses) Good for the awake patient who can be expected to have demonstrable respiratory distress following ventilator withdrawal.   

Bolus: 20-50 mg
Infusion: 10-100 mg/hr

References 

1. Bakker J, et al.  Why opioids and sedatives may prolong life rather than hasten death after ventilator withdrawal in critically ill patients.  Am J Hosp Pall Care 2008; 25: 152-154.
2. Campbell ML.  How to withdraw mechanical ventilation: a systematic review of the literature.  AACN Adv Crit Care 2007; 18(4); 397-403.
3. Jennerich AL. An approach to caring for patients and family of patients dying in the ICU.  Chest 2024;166(1):127-135.
4. Campbell ML, Templin T, Walch J.  A respiratory distress observation scale for patients unable to self-report dyspnea.  Journal of Palliative Medicine 2010; 13(3):285-289.
5. Chan JD, et al. Narcotic and benzodiazepine use after withdrawal of life support: Association with time to death? Chest. 2004; 126:286-293.
6. Adapted from: Emanuel LL, von Gunten CF, Ferris FF, eds.  Module 11: Withholding and Withdrawing Therapy.  The EPEC Curriculum:  Education for Physicians on End-of-life Care. Chicago, IL: The EPEC Project; 1999.  http://www.EPEC.net. 
7. Rubenfeld GD, Crawford SW. Principles and practice of withdrawing life-sustaining treatment in the ICU. In Managing Death in the Intensive Care Unit. Curtis JR and Rubenfeld GD, eds. New York, NY: Oxford University Press; 2001: pp127-147.
8. McWilliams K, et al. Propofol for terminal sedation in palliative care: a systematic review. J Palliat Med. 2010; 13:73-6. doi:10.1089/jpm.2009.0126.
9. The Joint Commission. Specifications Manual for Joint Commission National Quality Measures v2024A1. The Joint Commission website. Accessed January 10, 2024.
10. Treece, P. Standardized order sets for end of life care. Journal of Hospice & Palliative Nursing.  2007; 9(2): 70-71. 

Version History:  This Fast Fact was originally edited by David E Weissman MD.  2nd Edition published July 2005; 3rd Edition May 2015; 4th Edition in February 2025.
Conflicts of Interest: None to report.