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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3978_Библиотеки_им_академика_М_И_Перельмана
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care (turning, suctioning). Although some patients may be able to verbally or
nonverbally communicate their pain, the critically ill, intubated patient may not
communicate their level of pain adequately (Vender et al. 2004 ; Jacobi et al. 2002 ).
If intravenous opioid analgesia is required, fentanyl, hydromorphone, and mor-
phine are the recommended agents. Scheduled opioid doses or a continuous infu-
sion is preferred over an “as needed” regimen to ensure consistent analgesia.
Fentanyl or hydromorphone are preferred for patients with hemodynamic instability
or renal insuffi ciency. Morphine and hydromorphone are preferred for intermittent
therapy because of their longer duration of effect. There are no trials comparing the
various opioids to each other in critically ill patients. The choice of agent depends
upon the desired onset and duration of action and the potential adverse effects
(Vender et al. 2004 ; Jacobi et al. 2002 ).
NSAIDs or acetaminophen may be used as adjuncts to opioids in select patients.
Ketorolac therapy should be limited to a maximum of 5 days, with close monitoring
for the development of renal insuffi ciency or gastrointestinal bleeding. Other NSAIDs
(i.e., ibuprofen) may be used via the enteral route in appropriate patients (Table 2.8 ).
2.7 Sedating Agents
Sedation has become an integral part of critical care practice in minimizing patient
discomfort. Consequences of suboptimal sedation include the following: anxiety,
patient-ventilator dyssynchrony, agitation, and increased pain response. Adequate
sedation reduces the stress response, provides anxiolysis, and improves tolerance of
ventilatory support. Patient assessment should include the underlying problems and
the role of pain prior to initiation of therapy (Jacobi et al. 2002 ; Vender et al. 2004 ;
Ostermann et al. 2000 ).
The use of validated sedation scales improves consistency of medication adminis-
tration as well as the quality of sedation to enhance patient safety and comfort. The
routine use of a standardized assessment scales allow for a more precise medication
titration, reduction in the amount of sedative used, less vasopressor support, and shorter
duration of mechanical ventilation. Examples of validated ICU sedation scales include
the following: Ramsay sedation scale, sedation agitation scale (SAS), Vancouver inter-
active and calmness scale (VICS), Richmond agitation-sedation scale (RASS), and
Minnesota sedation assessment tool (MSAT) (Jacobi et al. 2002 ; Vender et al. 2004 ).
The use and titration of sedating agents is complex and requires a working knowl-
edge of the pharmacologic agents employed coupled with the consistent application of
validated sedation scales to achieve optimal outcomes. Large variation in dose require-
ments has been reported due to altered pharmacokinetic/pharmacodynamic properties
in the critically ill, tolerance issues, and differences in severity of symptoms. As a
result most agents are titrated to effect (i.e., RASS = −2), and therapy should always be
individualized for each patient (Jacobi et al. 2002 ; Vender et al. 2004 ).
Numerous studies show that sedation algorithms or guidelines decrease drug
costs, cause less hypotension and ventilator-associated pneumonia (VAP), decrease
aggregate dosing, and often decrease mechanical ventilation duration (Jacobi et al.
2002 ; Vender et al. 2004 ; Ostermann et al. 2000 ) (Table 2.9 ).
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Table 2.8 Analgesic agents
Drug
Dosing Common adverse effects
Comments
Fentanyl
Intermittent bolus dose :
Respiratory depression, depressed
consciousness, hallucinations, hypotension,
nausea/vomiting, decreased GI motility/
ileus, urinary retention
Preferred for a rapid onset of analgesia in
acutely distressed patients
25 mcg SQ/IV q2h prn pain (0.35–1.50
mcg/kg)
Withdrawal symptoms when moderate to
high doses are used for up to or more than
1 week
Individualize dose for each patient
Continuous infusion :
Virtually devoid of histamine-releasing
properties
25–300 mcg/h (0.7–10 mcg/kg/h) More rapid onset of action and a shorter
half-life than morphine
Usual starting dose 25–50 mcg/h; increase/
decrease rate by minimum of 25 mcg/h at
intervals no longer than Q 30 min
Renal failure does not appear to affect
pharmacokinetics
Titration parameter: pain scale Rigidity with high doses
Hydromorphone
Intermittent bolus dose :
Respiratory depression, depressed
consciousness, hallucinations, hypotension,
nausea/vomiting, decreased GI motility/
ileus, urinary retention
Individualize dose for each patient
0.5 mg SQ/IV q2h prn pain Withdrawal symptoms when moderate to
high doses are used for up to or more than
1 week
Available as PCA
Continuous infusion :
Effect of renal insuffi ciency on the
elimination of hydromorphone is unknown
1–20 mg/h (7–15 mcg/kg/h) More rapid onset of action and a shorter
half-life than morphine
Usual starting dose 1 mg/h; increase/
decrease rate by minimum of 0.5–1 mg/h at
intervals no longer than Q 30 min
Titration parameter: pain scale
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Morphine
Intermittent bolus dose :
Respiratory depression, depressed
consciousness, hallucinations, hypotension,
nausea/vomiting, decreased GI motility/
ileus, urinary retention
Individualize dose for each patient
2 mg SQ/IV q2h prn pain
(0.01–0.15 mg/kg)
Withdrawal symptoms when moderate to
high doses are used for up to or more than
1 week
Available as PCA
Continuous infusion :
Histamine release: fl ushing, tachycardia,
pruritus
Adjust dose for renal/liver dysfunction
1–50 mg/h (0.07–0.50 mg/kg/h) Rapid onset
Usual starting dose 1 mg/h; increase/
decrease rate by minimum of 0.5–1 mg/h at
intervals no longer than Q 30 min
Titration parameter: pain scale
Ketorolac < 65 y.o.: Injection site pain, abdominal pain,
constipation, diarrhea, fl atulence,
indigestion, nausea/vomiting, headache
Use with caution in patients with
preexisting renal insuffi ciency
30 mg IV/IM × 1 or 30 mg IV/IM q6h
(scheduled or PRN)
Use lowest effective dose for the shortest
period of time
Max dose: 120 mg/day; Max duration:
5 days
> 65 y.o. or weight < 50 kg:
15 mg IV/IM × 1 or 15 mg IV/IM q6h
(scheduled or PRN)
Max dose: 60 mg/day; Max duration:
5 days
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Table 2.9 Sedating agents
Drug
Onset after IV dose Dosing
Comments/adverse effects
Dexmedetomidine 10–30 min
IV bolus : Duration not to exceed 24 h
NOT recommended in ICU patients
Adverse effects: bradycardia, bradyarrhythmia,
hypotension
Continuous infusion :
Dosage should be individualized
0.2–0.7 mcg/kg/h Consider dose reduction in patients with renal impairment
and/or hepatic impairment due to reduced clearance
Increase/decrease rate by 0.1 mcg/kg/h at
intervals no shorter than Q 20 min
Consider dose reduction in patients >65 y.o.
Titration parameter: RASS and BIS (?) Initial bolus dose NOT recommended due to potentially
severe acute changes in heart rate and blood pressure
especially when patient is receiving concurrent sedatives/
analgesics or when converting from alternate sedative
therapy
Lorazepam 5–20 min
Intermittent bolus dose :
Slower onset than midazolam
0.02–0.06 mg/kg q2h prn agitation Adjust dose in renal/liver impairment
Continuous infusion :
Higher doses and use in patients with renal dysfunction
may increase the risk of acidosis from the accumulation of
propylene glycol (diluent)
0.5–20 mg/h (0.01–0.1 mg/kg/h) Individualize dose for each patient
Increase/decrease rate by minimum of 1 mg/h
at intervals no longer than Q 2 h
Titration parameter: RASS and BIS (?)
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Midazolam 2–5 min
Intermittent bolus dose :
Preferred for rapid sedation of acutely agitated patients
0.02–0.08 mg/kg q1h prn agitation Produces unpredictable awakening and time to extubation
when infusions continue longer than 48–72 h or in patient
with renal dysfunction
Continuous infusion :
Active metabolite
0.5–20 mg/h (0.04–0.2 mg/kg/h) Individualize dose for each patient
Increase/decrease rate by minimum of
0.5 mg/h at intervals no longer than Q 30 min
Titration parameter: RASS and BIS (?)
Propofol 1–2 min
Continuous infusion :
NO analgesic properties
10–75 mcg/kg/min Preferred when rapid awakening is necessary, neurosurgery
patients or patients who require neurological assessment
Increase/decrease by minimum of 5 mcg/kg/
min at intervals no less than 5 min
Higher doses and sedation >48 h prolongs the awakening
time
Titration parameter: RASS and BIS (?) Baseline LFTs and TG level and repeat every 3–5 days
Individualize dose for each patient
The potential for benzodiazepine and propofol withdrawal should be considered after high doses or more than approximately 7 days of continuous therapy.
Doses should be tapered systematically to prevent withdrawal symptoms
Table 2.9 (continued)
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2.8 Neuromuscular Blocking Agents (NMBAs)
Neuromuscular blocking agents play an important but limited role in the ICU. As
per the American College of Critical Care Medicine (ACCM) of the Society of
Critical Care Medicine (SCCM) Revised Clinical Practice Guidelines, neuromuscu-
lar blocking agents should be used for an adult patient in an ICU to manage ventila-
tion, manage increased ICP, treat muscle spasms, and decrease oxygen consumption
only when all other means have been tried without success.
Similar to sedation and analgesia, management of neuromuscular blockade
requires individualized approach. Patient-based drug selection, identifi cation of
the goal of therapy, and monitoring for safety and effectiveness with titration of
drugs to the lowest effective dose for the shortest possible duration are necessary
to provide optimal outcomes (Murray et al. 2002 ; Sessler 2005 ). Before initiating
neuromuscular blockade, patients should be medicated with appropriate sedative
and analgesic drugs to provide adequate sedation and analgesia in accordance
with the physician’s clinical judgment to optimize therapy (Murray et al. 2002 ;
Vender et al. 2004 ).
Patients receiving neuromuscular blocking agents should be assessed both clini-
cally and by TOF monitoring with a goal of adjusting the degree of neuromuscular
blockade to achieve one or two twitches. To ensure deep sedation, neuromuscular
blocking agents must be stopped intermittently to observe behavior, and strong con-
sideration should be given to using an objective monitor, such as the bispectral
index (BIS). Neuromuscular blocking agents should never be used as a substitute
for sedation (Murray et al. 2002 ; Sessler 2005 ).
In general, use of intermittent dosing to ensure easy return of muscle activity is
preferable to continuous infusions. Daily drug interruption is recommended to
allow for neurologic evaluations, ensure adequate sedation, and reassess the need
for ongoing blockade (Murray et al. 2002 ; Sessler 2005 ; Vender et al. 2004 ).
The most important toxicity of neuromuscular blockade is persistent skeletal
muscle weakness, and neuromuscular blocking agents should be stopped as soon as
they are no longer required (Murray et al. 2002 ; Sessler 2005 ) (Table 2.10 ).
2.8.1 Monitoring
The response to neuromuscular blocking agents can be signifi cantly variable.
Variability of response can increase to a greater degree in patients with organ dys-
function or other neuromuscular pathologies. It is imperative that neuromuscular
blockade is properly monitored (i.e., determine drug effect, determine the need for
additional doses, and confi rm recovery) through the use of a peripheral nerve stimu-
lator. Typically, the stimulator is placed over the ulnar nerve, and a train-of-four
(TOF) shock pattern (four twitches at half-second intervals and a tetanic stimulus at
50 or 100 cycles per second) is used. Currently, there is no universal standard for
twitch monitoring. The choice of the number of twitches necessary for “optimal”
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Table 2.10 Neuromuscular blocking agents (NMBAs)
Succinylcholine Pancuronium Vecuronium Cisatracurium
Atracurium
Initial dose (mg/kg) 0.6 0.06–0.1 0.08–0.1 0.1–0.2 0.4–0.5
Duration (min) 10 90–100 35–45 45–60 25–35
Infusion dose (mcg/
kg/min)
N/A 1–2 0.8–1.2 1–10 2–12
Recovery (min) 10–20 120–180 45–60 90 40–60
Renal failure No change Increased effect Increased effect No change No change
Hepatic failure Increased effect (decrease
dose)
Mild increased effect Variable Minimal to no change Minimal to no change
Active metabolites Yes Yes Yes No No
Adverse effects Apnea Apnea Anaphylaxis Bradyarrhythmia Anaphylaxis
Bradyarrhythmia Bronchospasm Apnea Bronchospasm Bradyarrhythmia
Cardiac arrest Hypertension Bronchospasm Hypotension Bronchospasm
Cardiac dysrhythmia Prolonged neuromus-
cular block
Hypotension Edema
Hyperkalemia Respiratory failure
Tachyarrhythmia
Muscle weakness Erythema
Hypersensitivity reaction Prolonged neuromuscular
block
Hives
Malignant hyperthermia Tachyarrhythmia Hypersensitivity reaction
Prolonged neuromuscular
block
Hypotension, at larger
than recommended doses
Respiratory depression Laryngeal spasm
Rhabdomyolysis
Tachyarrhythmia
Muscle weakness
Paralysis
Tachyarrhythmia, at
higher doses
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blockade is infl uenced by the patient’s overall condition and level of sedation.
The goal is two out of four twitches (75–80 % of blockade) (Murray et al. 2002 ).
The number of twitches counted represents the percentage of neuromuscular
blockade:
4 twitches = less than 75 % blockade
3 twitches = 75 % blockade
2 twitches = 75–80 % blockade
1 twitch = 90 % blockade
It is diffi cult to assess pain and sedation if the patient is receiving NMBA, but
patients must be medicated for pain and anxiety, despite the lack of obvious symp-
toms or signs (Murray et al. 2002 ).
In common practice, sedative and analgesic drugs are adjusted until the patient
does not appear to be conscious and then NMBA are administered.
2.8.2 Adjunct Therapy While Receiving NMBAs
DVT prophylaxis (heparin 5,000 units SQ q8–12 h), physical therapy, prevention
of keratitis and corneal abrasion (eye patches, taping eyelids shut, application of
lubricant eye drops/ointment (i.e., Lacri-lube
®
to both eyes QID)), as well as repo-
sitioning to avoid decubitus ulcers
2.9 ICU Delirium
As many as 80 % of ICU patients have delirium, characterized by an acutely chang-
ing or fl uctuating mental status, inattention, disorganized thinking, and an altered
level of consciousness that may or may not be accompanied by agitation. Routine
assessment for the presence of delirium is recommended (i.e., CAM-ICU, ICDSC)
( http://icudelirium.org/index.html 2012 ).
Non-pharmacologic options for the prevention and treatment of ICU delirium
include removal of deliriogenic drugs, frequent reorientation, restoration of sleep/
wake cycles, timely removal of catheters, early mobilization, and minimization of
unnecessary noise/stimuli (Bruno and Warren 2010 ).
Currently , there are no FDA approved drugs for the treatment of ICU delirium .
The American Psychiatric Association guidelines suggest that antipsychotics may be
used for delirium; however, there are no formal recommendations for ICU delirium.
Haloperidol is the preferred agent for the treatment of delirium in critically ill
patients. Although commonly used in clinical practice on a “prn” basis, limited dos-
ing information for ICU delirium results in variable doses.
Large randomized, placebo-controlled trials with a characteristic ICU population
are needed for defi nitive evidence of effi cacy as well as to establish appropriate dos-
ing of atypical antipsychotics. The benefi t of these agents is the lower incidence of
QTc prolongation and neurologic adverse effects compared with haloperidol
(Table 2.11 ).
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Table 2.11 Agents for ICU delirium
Drug
Onset Dosing
Adverse effects/comments
Haloperidol 3–20 min 2–10 mg IV push every
30 min then 1–5 mg
IVq6h
Monitor for electrocardiographic changes
QT interval prolongation and arrhythmias
0.03–0.15 mg/kg Q6h Extrapyramidal side effects
Discontinue in patients
with QTc >500 ms
Neuroleptic malignant syndrome (rare)
Lowers seizure threshold
Black box warning: increased mortality in
elderly with dementia-related psychosis
Causes sedation
Olanzapine No data 2.5–5 mg PO QHS Monitor for electrocardiographic changes
QT interval prolongation and arrhythmias
≤60 min 5–10 mg IM Extrapyramidal side effects
Discontinue in patients
with QTc >500 ms
Lowers seizure threshold
Hyperglycemia
Peripheral edema
Causes sedation
Quetiapine No data 25–50 mg PO BID Monitor for electrocardiographic changes
QT interval prolongation and arrhythmias
Discontinue in patients
with QTc >500 ms
Extrapyramidal side effects
Neuroleptic malignant syndrome (rare)
Lowers seizure threshold
Neutropenia
Hyperglycemia
Causes sedation
Ziprasidone No data 20 mg PO q4h or Monitor for electrocardiographic changes
QT interval prolongation and arrhythmias
≤60 min 40 mg PO q6h Extrapyramidal side effects
10 mg IM Neuroleptic malignant syndrome
Discontinue in patients
with QTc >500 ms
Lowers seizure threshold
Hyperglycemia
Bone marrow depression
Many drug-drug interactions
There is limited trial data establishing safety, effi cacy, or appropriate dosing of atypical
antipsychotics
2.10 ICU Hyperglycemia
Historically, hyperglycemia was not routinely controlled in intensive care units
(ICU). More recent evidence indicating that uncontrolled hyperglycemia is
associated with poor outcomes has prompted efforts to routinely correct and prevent
hyperglycemia in critically ill patients.
Hyperglycemia associated with critical illness (also called stress hyperglycemia
or stress diabetes) is a consequence of many factors, including increased cortisol,
catecholamines, glucagon, growth hormone, gluconeogenesis, and glycogenolysis.
Insulin resistance may also be a contributing factor, since it has been demon-
strated in more than 80 % of critically ill patients (Falciglia et al. 2009 ; Van den
Berghe et al. 2001 ).
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Hyperglycemia, defi ned as a blood glucose level greater than 180–200 mg/dL, is
associated with poor clinical outcomes. Intensive insulin therapy (target blood glu-
cose range of 80–110 mg/dL) signifi cantly increases the incidence of severe hypo-
glycemia. Its effect on mortality is uncertain, since various randomized trials have
reported increased mortality, no effect on mortality, or decreased mortality (Falciglia
et al. 2009 ; Griesdale et al. 2009 ).
Prevention of uncontrolled hyperglycemia is a desirable intervention; however,
the optimal blood glucose range remains controversial. As per the 2012 ADA guide-
lines, insulin therapy should be initiated for persistent hyperglycemia starting at a
threshold of no greater than 180 mg/dL with the goal of 140–180 mg/dL recom-
mended for the majority of critically ill patients.
Regularly scheduled administration of insulin is a proactive approach to treat
hyperglycemia and is preferable to a reactive administration regimen (i.e., “sliding
scale” insulin) in response to an elevated glucose concentration. If a subcutaneous
insulin regimen fails to maintain blood glucose within the target range, consider
utilizing a continuous infusion of intravenous insulin. Despite the available litera-
ture, a widely accepted insulin regimen has not been established.
2.11 Miscellaneous
2.11.1 Medication Reconciliation
Medication reconciliation is the process of comparing a patient’s medication orders
to all of the medications that the patient has been taking. Medication reconciliation
is intended to identify and resolve discrepancies—it is a process of comparing the
medications a patient is taking (and should be taking) with newly ordered medica-
tions. This comparison is done to avoid medication errors such as omissions, dupli-
cations, dosing errors, or drug interactions and the need to continue current
medications. It should be done at every transition of care in which new medications
are ordered or existing orders are rewritten.
2.11.2 Stress Ulcer Prophylaxis
Stress ulcerations usually occur in the fundus and body of the stomach but some-
times develop in the antrum, duodenum, or distal esophagus. They tend to be shal-
low and cause oozing of blood from superfi cial capillary beds. Deeper lesions may
also occur, which can erode into the submucosa and cause massive hemorrhage or
perforation.
The guidelines recommend stress ulcer prophylaxis (SUP) for ICU patients with
any of the following characteristics: coagulopathy, mechanical ventilation for more
than 48 h, history of GI ulceration or bleeding within the past year, and two or more
minor risk factors. Minor risk factors include sepsis, ICU admission lasting >1
week, occult GI bleeding lasting ≥6 days, and glucocorticoid therapy (ASHP 1999 ).
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