Page 245 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 22: Pain Control, Sedation, and Use of Muscle Relaxants 149

to be accounted for when considering the efficacy and concentrations. Such protocols ensure adequate analgesia and sedation using frequent
These include volume of distribution, clearance, and organ function. assessments of patient needs with goal-directed titration of analgesics
The volume of distribution cannot be assumed in the critically ill as and sedatives. Alternatively, a routine protocol of daily interruption of
many patients have received large volumes of resuscitation fluids, or continuous sedative infusions can reduce many of the complications of
conversely, been diuresed aggressively. Another key point to consider is sedation in the ICU setting, including duration of mechanical ventila-
the pharmacodynamics of the drug itself and whether it is hydrophilic tion and ICU length of stay (Figs. 22-2 and 22-3). 55,65,66 Such a strategy
or lipophilic. For instance, benzodiazepines are “short acting” due to allows patients to spend a substantial portion of their ICU time awake
their lipophilic nature 53,54 ; however, when administered for a long-time and interactive, potentially reducing the amount of sedative and opiate
period, these drugs accumulate in tissue (especially adipose) stores with given, as well as reducing the need for diagnostic studies (eg, head CT
a resulting prolonged clinical effect. 51,55-58 Other circumstances that scan) to evaluate unexplained alterations in mental status.
confound prediction of the pharmacologic behavior of sedatives and Such protocol-driven sedation strategies allow a focused downward
analgesics include altered hepatic and/or renal function. This is a titration of sedative infusion rates over time, streamlining administration
59
large concern especially since many sedatives have active metabolites of these drugs and minimizing the tendency for accumulation. Protocols
(eg, midazolam). Of note, when patients initially present to the ICU, the may allow the depth of sedation to be decreased without compromising
ability to predict organ function is poor and may not be detectable dur- the stated goals of sedation. This strategy may allow clinicians to minimize
ing the acute phase. This can lead to accumulation of medications. Other sedative accumulation. Initially, the thought of decreasing or stopping sed-
concerns include polypharmacy in the ICU with complex drug-drug atives in a critically ill patient who has been agitated may be unsettling. As
interactions, altered protein binding, and circulatory instability. The such, clinicians may sedate patients aggressively early in their ICU course
multicompartmental pharmacokinetics typical in critically ill patients and maintain the same level of deep sedation indefinitely. A daily holiday
defy simple bedside pharmacokinetic profiling. As such, titration of from sedatives can eliminate the tendency to “lock in” to a high sedative
sedatives and analgesics against discernible clinical end points, while infusion rate. When sedative infusions are decreased or stopped, tissue
imprecise, is the only reliable strategy. Further confounding administra- stores can redistribute drug back into the circulation. The interruption of
tion of sedatives in the ICU is the dramatic difference between extremes sedative infusions sometimes may lead to abrupt awakening and agitation.
of sedation. Frequently, oversedated patients are easier to manage than This must be anticipated by the ICU team to avoid complications such as
undersedated patients, and in an effort to avoid unmanageable agita- patient self-extubation; if excessive agitation is noted, sedatives should
tion, clinicians may be heavy-handed when sedating agitated patients. be restarted. Although the attempt at waking and communicating with a
However, deep sedation, even early in critical illness, may lead to patient may fail on a given day, this does not portend inevitable failure on
adverse outcomes. Recent guideline recommendations promote light all subsequent days. When awakening patients from sedation, one need
60
sedation. Heavier sedation can contribute to increased ventilator days, only bring patients to the brink of consciousness—able to follow simple
7
increased risk of developing delirium and ultimately long-term neuro- commands (ie, open eyes, squeeze hand, track with eyes, open mouth/
cognitive and neuromuscular deficits. 61 stick out tongue) without precipitating excessive agitation. Once objec-
It is not uncommon for some critically ill patients to require extraor- tive signs of consciousness are demonstrated, it is reasonable to restart
dinarily high doses of sedatives to achieve tranquility; such doses may sedatives at the first sign of agitation. If after discontinuing the sedative
be much greater than quoted in the literature and recommended by drug infusion the patient requires resedation, we recommend restarting the
manufacturers. This may be due to drug tolerance and the requirement infusion at 50% of the previous dose. Adjustments from this starting point
62
for more medication to achieve the same state of comfort. It is impor- can be individualized to patient needs. 66
tant to note that pain and need for sedation are dynamic. Patients will It is clear that sedatives may have an impact on the duration of
fluctuate throughout their time on these medications and the “correct mechanical ventilation. 55,64 Protocolized sedation strategies may reduce
dose” for 1 hour may not be enough or may be too little the next. Indeed, the duration of mechanical ventilation by allowing earlier recognition
occasional patients may even require pharmacologic paralysis to achieve of patient readiness to undergo a spontaneous breathing trial. The use
synchrony with mechanical ventilation. 63 of a daily spontaneous waking trial, followed by a daily spontaneous
As evidence-based treatment strategies for many common condi- breathing trial, should be implemented widely in the care of critically ill
tions seen in critical illness have emerged and sicker patients continue patients requiring mechanical ventilation. 66
to demonstrate improved outcomes in the ICU, more aggressive lev- When discussing heavy sedation, the primary agents utilized are
els of sedation and analgesia may be necessary. This is particularly either propofol or benzodiazepines, such as midazolam or lorazepam.
likely for patients managed with unconventional ventilator strategies A newer agent, dexmedetomidine, has been studied and is labeled a lighter
(eg, permissive hypercapnia, low tidal volumes, prone positioning, and sedative. It is an α agonist and provides a lighter sedative effect with the
2
pressure-controlled ventilation) because these strategies may be inher- physiological benefit of no respiratory depression. A multicenter study
ently distressing to many patients. compared the effects of dexmedetomidine and midazolam on sedation in
The use of deep sedation carries a heavy price because the neurologic mechanically ventilated patients and found that there was no difference
examination is severely limited in these patients. Ideally, a head-to-toe between the sedatives in regard to time within target RASS, however, there
daily assessment for the presence of organ failure should be routine for was an increase in delirium in the midazolam group. Additionally, time to
every critically ill patient. This is particularly so during resuscitative phases extubation was increased with the midazolam group (3.7 vs 5.6 days). 61
of ICU care, when assessing the adequacy of end-organ perfusion and One study assessed a protocol of no sedation (morphine only) com-
function is of paramount importance. The mental status examination is pared to daily interruption of sedation (control group) in mechanically
an important gauge of brain perfusion. Since brain injury is a devastating ventilated critically ill patients. In the control group, patients received
complication of critical illness, acute cerebral dysfunction must be detected morphine, propofol, or midazolam if intubated for longer than 48 hours.
quickly and corrected, if possible, before permanent injury takes place. The They found that the patients randomized to the no sedation group had an
veil of sedation severely handicaps a clinician’s ability to serially follow a increase in days without ventilation. Every patient received 1:1 nursing
patient's neurologic condition. Communication and thorough physical care, an arrangement that may not be feasible at all centers. 67
examination may detect problems early on and obviate urgent diagnostic
studies and therapeutic interventions after a problem has advanced. ■ DRUGS FOR SEDATION OF MECHANICALLY VENTILATED PATIENTS
A protocol-driven approach to sedation has been shown to alleviate
many of the problems mentioned earlier. A protocol directed by bedside Opiates: Opiate receptors are found in the central nervous system,
nurses can shorten the duration of mechanical ventilation, ICU and as well as in peripheral tissues. There are several classes of receptors,
hospital length of stay, and the need for tracheostomy (Fig. 22-1). but the two most clinically important are the μ and κ receptors. The
64

section02.indd 149 1/13/2015 2:05:03 PM