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How to reduce anxiety and improve comfort while not oversedating.

A 70-year-old male comes to the emergency department via EMS febrile, with worsening respiratory distress and altered mental status. You quickly diagnose him as having severe sepsis stemming from pneumonia, and initiate treatment. After setting up and preoxygenating him, you have first-pass success on your intubation, pat yourself on the back, and admit him to the ICU. But your nursing manager then informs you that the hospital is full, including the ICU. So now your severely septic patient will be boarding in the ED. He quickly starts to get hypotensive on your sedation and you can only sweat and wonder, “How am I supposed to manage him now?”

Once mechanical ventilation has been initiated, the physician’s initial goals are to relieve patient anxiety and keep them comfortable. In “The ICU Book,” Marino states “the common denominator in these conditions (anxiety and delirium) is the absence of a sense of well-being.”

Reducing anxiety on a ventilated patient is challenging. Double breathing the ventilator, pulling at lines and persistent tachycardia are all obvious signs of anxiety. In the “good old days,” trying to achieve those two goals under these conditions was often met with a slight dose of paralysis – vecuronium at times – while maintaining ventilator synchrony, mixed with a few pushes of benzodiazepines to relieve anxiety and hopefully introduce some amnesia.

Fortunately, as emergency medicine knowledge progressed, so did pharmacology, and now the idea of paralyzing an awake patient brings chills to us all. Unfortunately, while the use of opiates and benzodiazepines post-intubation may be a step forward, they come with their own unique set of complications. The normotensive patient that becomes hypotensive on sedation is markedly common, and unfortunately many respond by simply adding some wrist restraints and cutting back on drips. The other side of the coin occurs just as often — patients overmedicated with enough sedation to knock out a small elephant. These dilemmas occur often in the ED and even in many ICUs, but with new ICU guidelines on sedation, the ED can take evidence-based decisive measures to improve patient care for the most critically ill patients1.

Goal #1: Pain Relief

The first goal is easily the most important and most practical: a hard plastic tube in the oropharynx hurts, so give pain relief. While the concept of pain is simple to understand, it is easy for a physician to forget to provide analgesia. Providers will often put on the milky potion of diprivan and forget that it has no analgesic properties. Similarly, if the patient becomes hypotensive, the Fentanyl drip will be reduced, instead of maintaining a comfortable patient and starting vasopressors to main hemodynamics. Some departments may have restrictions on certain opiate drips, such as Fentanyl. In those cases infusions of Morphine can be used. Fentanyl has the unique advantage of creating more than analgesia – it can create hypnosis for certain patients. Fentanyl, as a synthetic opioid, also has the benefit of having no histaminergic reactions, nor does it have active metabolites2. For those looking for up-to-date pharmacology, remifentanil (Ultiva®) has entered the market, and provides more rapid onset and elimination due to its plasma-dependent metabolism, safe for the renal or hepatic impaired (table 1). In the end, analgesia is the first line and sometimes it can be everything.

Sedation Scales

Before discussing the second point, one key scoring system must be understood. The Richmond Agitation Sedation Scale (RASS) is a useful tool for assessing ventilated patient arousability (table 2). Rather than having only the extremes – pulling out the tube versus completely limp and comatose – the goal now within the ICU is to maintain a patient comfortably sedated at a RASS of anywhere from 0 to -3. Understanding the RASS makes sedation more plausible and greatly improves communication when signing out that tough sick, intubated patient. Other scales, such as the Riker Sedation-Agitation Scale (SAS) and the Ramsay scale, are also available. The goal is to have an objective scale that can be used to communicate between the ED and the ICU.

Goal #2: Avoid Delirium

The second goal is more controversial, but just as important – avoiding delirium. In the past, pushes of lorazepam appeared to be effective. The agitated patient with elevated peak pressures would roll their eyes back and relax on the ventilator. Unfortunately, the long-term effects were hidden to the ED. There is some literature that has come to show benzodiazepines may worsen delirium17. Delirium in the ICU may seem like a distant thought to the ED physician, but literature has shown that delirium leads to longer ICU stays and increased mortality18-20.

Unfortunately, we only have a theory as to why benzodiazepines cause delirium, which may come down to their effect on sleep. Benzodiazepines act directly on GABA receptors in the brain, inducing sleep at the second step, while dexmedetomidine acts one step above by reducing norepinephrine release from the locus ceruleus thereby creating a more natural sleep pattern21. So, with the new understanding that benzodiazepines can worsen delirium, and delirium worsens outcomes, why not simply use a good old Fentanyl drip and forget the rest? In actuality, this may be a very practical solution23,24.

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Vent Synchrony

Unfortunately, patients undergoing intubation in the ED are not the pristine, well-prepped cases seen in the OR. Rather, they’re ill patients with shock, bleeds, severe dyspnea, and just severe “badness,” making vent synchrony a challenge.

Once we have pain taken care of, our next step is to improve vent synchrony without using benzodiazepines. Two important medications give us this ability, propofol and dexmedetomidine. Propofol (Diprivan®), well-known to most ED staff, has a known profile for being quick on and quick off with a common adverse effect of hypotension. Dexmedetomidine (Precedex®) is the new kid on the block and offers a variety of advantages, including analgesic effects, anxiolysis, hypnosis, and no respiratory depression. The two major downsides of dexmedetomidine are bradycardia, which is dose dependent and can be avoided, and cost. It remains one of the most expensive medications on formulary in many hospitals. At the end of the day, however, the goal of maintaining vent synchrony trumps other goals; if propofol or dexmedetomidine is not available, pushes of benzodiazepines, like Midazolam, are warranted.

Useful Sedatives

As pointed out earlier, ED patients can be a challenging group to manage medically, let alone on the ventilator with sedation. Fortunately, there are four unique situations where sedatives can give us a hand. In status epilepticus and alcohol withdrawal, think of Diprivan, offering further GABA-ergic effects, possibly adding to the previous pushes of benzodiazepines. In the status asthmaticus, consider the classic medication Ketamine, useful for its sympathomimetic effects (table 1). Push doses of Ketamine may also be useful in that hypotensive trauma patient that is on the way to CT instead of the OR. Unfortunately, the jury is still out on Ketamine as a drip for the ventilated ICU patient. Lastly, when none of the above occurs and your patient is simply critical and agitated, put on some dexmedetomidine.

Returning back to our case, we’ve intubated our septic patient who was placed on Fentanyl. Being opiate naive, the patient has some hypotension on Fentanyl, but responds to crystalloid fluid. After several hours of boarding, you note an anxious patient pulling at lines. Unable to redirect him, you ask the nurse to start a drip of dexmedetomidine. Afterward, your patient is calm, arousable to name and resting comfortably. The ICU bed finally opens up, your patient gets transported, and you pat yourself on the back for handling another critical patient with calm and finesse.

TABLE 1: ANALGESIA AND SEDATION DOSAGES

Propofol (Diprivan®)          

Bolus: 5 mcg/kg/min (0.3 mg/kg/hr) IV infusion for 5 min3

Infusion: Titrate in 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/hr) increments to achieve desired level of sedation; allow minimum of 5 min between dose adjustments; usual maintenance rates 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/hr) or higher 3

A/E: Hypotension, respiratory depression

 

Midazolam (Versed®)         

Bolus: 0.01 to 0.05 mg/kg IV administered over several minutes; may repeat at 10- to 15-minute intervals until adequate sedation is achieved4           

Infusion: Initiated at a rate of 0.02 to 0.1 mg/kg/hr; may adjust rate up or down by 25% to 50% of initial infusion rate to achieve adequate sedation4

A/E: Hypotension, respiratory depression

 

Dexmedetomidine (Precedex®)    

Bolus: Loading infusion of 1 mcg/kg IV over 10 minutes; no loading dose required when converting from alternate sedative therapy5          

Infusion: Maintenance, 0.2 to 0.7 mcg/kg/hr continuous IV infusion titrated to desired clinical effect5

A/E: Hypotension, bradycardia      

 

Haloperidol (Haldol®)        

Bolus: Bolus with infusion: 0.5 mg bolus followed by 0.1 mg/hr infusion7                  

A/E: Prolonged QT, Extrapyramidal Symptoms   

Intermittent Dosing: 2.5 mg every 8 hours, can have added boluses of 2.5 mg – 5 mg with daily max of 10 mg6

 

Remifentanil (Ultiva®)       

Bolus: Continuous infusion, 0.1 to 0.15 mcg/kg/min IV initially (using ideal body weight)8-11      

Infusion: Titration to a MAX dose of 0.2 to 0.4 mcg/kg/min IV8-11     

A/E: Hypotension, bradycardia      

 

Fentanyl citrate                    

Infusion: Continuous infusion, 0.7 to 10 mcg/kg/hr IV12

A/E: Hypotension, accumulates in fatty tissue     

Intermittent Dosing: 0.35 to 1.5 mcg/kg IV every 0.5 to 1 hour, if inadequate pain relief consider bolus and increasing drip by 25-50%12

 

Morphine sulfate                 

Infusion: 0.07 to 0.5 mg/kg/hr IV13

A/E: Hypotension, respiratory depression

Intermittent Dosing: 0.01 to 0.15 mg/kg IV every 1 to 2 hours, if inadequate pain relief consider bolus and increasing infusion13

 

Ketamine Based on general anesthesia/procedural sedation dosages 

Bolus: Induction, 1 to 2 mg/kg IV over 1 to 2 min, may be followed by 0.25 to 0.5 mg/kg IV every 5 to 10 min as needed14    

Infusion: 0.01to 0.03 mg/kg/min continuous IV infusion          

A/E: Sympathomimetic effects, laryngospasm     

 

References

1. Barr J, Fraser GL, 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 Jan;41(1):263-306

2. Marino, Paul L. The ICU book / Paul L. Marino; with contributions from Kenneth M. Sutin; illustrations by Patricia Gast. 3rd ed.

3. Product Information: DIPRIVAN(R) IV injectable emulsion, propofol IV injectable emulsion. APP Pharmaceuticals LLC, Schaumburg, IL, 2008.

4. Product Information: midazolam HCl IM, IV injection solution, midazolam HCl IM, IV injection solution. Hospira, Inc (Per DailyMed), Lake Forest, IL, 2009.

5. Product Information: Precedex(TM) intravenous injection, intravenous injection concentrate, dexmedetomidine HCl intravenous injection, intravenous injection concentrate . Hospira, Inc. (per FDA), Lake Forest, IL, 2013.

6. Product Information: Precedex (TM) intravenous injection, intravenous injection concentrate, dexmedetomidine HCl intravenous injection, intravenous injection concentrate . Hospira, Inc. (per FDA), Lake Forest, IL, 2013.

7. Page VJ, Ely EW, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2013 Sep;1(7):515-23

8. Wang W1, Li HL, et al. Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: a randomized controlled trial. Crit Care Med. 2012 Mar;40(3):731-9

9. Futier E, Chanques G, Cayot Constantin S, et al: Influence of opioid choice on mechanical ventilation duration and ICU length of stay. Minerva Anestesiol 2012; 78(1):46-53.

10. Spies C, Macguill M, Heymann A, et al: A prospective, randomized, double-blind, multicenter study comparing remifentanil with fentanyl in mechanically ventilated patients. Intensive Care Med 2011; 37(3):469-476.

11. Dahaba AA, Grabner T, Rehak PH, et al: Remifentanil versus morphine analgesia and sedation for mechanically ventilated critically ill patients: a randomized double blind study. Anesthesiology 2004; 101(3):640-646.

12. Muellejans B, Lopez A, Cross MH, et al: 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(1):R1-R11.

13. Chinachoti T, Kessler P, Kirkham A, et al: Remifentanil vs morphine for patients in intensive care unit who need short-term mechanical ventilation. J Med Assoc Thai 2002; 85 Suppl 3:S848-S857.

14. Jacobi J, Fraser GL, Coursin DB, et al: Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 2002; 30(1):119-141.

15. Bahn EL & Holt KR: Procedural sedation and analgesia: a review and new concepts. Emerg Med Clin North Am 2005; 23(2):503-517.

16. Sessler CN, Gosnell MS, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002 Nov 15;166(10):1338-44.

17. Ely EW, Truman B, et al. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). Am J Respir Crit Care Med. 2002 Nov 15;166(10):1338-44.

18. Fraser GL, Devlin JW, 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 Sep;41(9 Suppl 1):S30-8

19. Pisani MA, Kong SY, et al. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med. 2009 Dec 1;180(11):1092-7

20. Shehabi Y, Bellomo R, et al. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012 Oct 15;186(8):724-31

21. Girard TD, Kress JP, 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 Jan 12;371(9607):126-34

22. Johnson T. Critical Care Pharmacotherapeutics, Jones & Bartlett Publishers, Feb 8, 2012, chapter 5, pg 92 – 95

23. Strøm T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010 Feb 6;375(9713):475-80

24. Devabhakthuni S, Armahizer MJ, Dasta JF, Kane-Gill SL. Analgosedation: a paradigm shift in intensive care unit sedation practice. Ann Pharmacother. 2012 Apr;46(4):530-40

 

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