Nursing Capstone - EBP project

Running Head: PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 1

Alteration of Pharmacologic Therapy to Prevent Delirium

in the Adult Intensive Care Unit

Indiana University School of Nursing

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 2

Alteration of Pharmacologic Therapy to Prevent Delirium

in the Adult Intensive Care Unit

Intensive Care Unit (ICU) delirium has been a topic of increasing interest in the critical

care community over the last several years. While advances in the care of critically ill patients

continue to improve overall survival and morbidity outcomes, ICU delirium continues to

contribute to an additional four to 16 billion dollars annually in increased healthcare costs and is

associated with profound morbidity and mortality independent of other ICU diagnoses.

Additionally, well-designed, large-scale research has been limited, usually reporting conflicting

results in terms of risk factors, prevention, and treatment (Barr et al., 2013).

It is well understood that delirium is considered a major public health problem affecting

20-50% of non-mechanically ventilated ICU patients and up to 60-80% of those who are critical

enough to require mechanical ventilation for respiratory support (Shehabi et al., 2010). As a

disease state, the incidence is difficult to directly pinpoint because it can often go unrecognized

or symptoms may be attributed to another disease process (Girard, Pandharipande, & Ely, 2008).

The diagnosis of delirium requires at least two components. First, the development of a

disturbance in level of consciousness; meaning the patient has reduced awareness or clarity. In

addition, the patient must exhibit either a change in cognition with subsequent memory deficit,

disorientation, or language disturbance, or, there must be the development of a perceptual

disturbance, such as a delusion or hallucination. It is important to acknowledge that delirium has

an acute onset with a fluctuating course, and thus is distinguishable from dementia and general

cognitive impairment (Barr et al., 2013).

While the overall diagnosis describes the main symptoms a patient with delirium may

exhibit, additional symptoms are associated with two separate subtypes. Hyperactive delirium is

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 3

characterized by the addition of agitation, restlessness, and combativeness, while hypoactive

delirium may include symptoms such as withdrawal, flat affect, apathy, lethargy, and diminished

responses. Mixed subset delirium may present with components of each. Additional symptoms

may include sleep disturbances, abnormal psychomotor activity, and emotional disturbances

(Barr et al., 2013; Bruno & Warren, 2010). While this review focuses primarily on delirium in

the ICU, it may occur in non-ICU patients as well.

The exact cause of delirium has been widely debated and is not quite clear. What is

currently understood is that there are several risk factors that have been associated with its

development, including pre-existing patient factors, factors relating to acute illness, and

iatrogenic factors. It should be noted that many studies evaluating links between these factors

and the development of delirium are conflicting (Girard et al., 2008). Generally accepted pre-

existing risk factors include: visual or hearing impairment, malnutrition, history of substance

abuse or home use of psychoactive medications, renal or liver impairment, hypertension, and

malnutrition. Risk factors related to acute illness may include: sepsis or infection, withdrawal

symptoms, dehydration, hypoxemia, hypotension, hypo- and hyperthermia, electrolyte and/or

glucose imbalances, acidosis, high transfusion requirements, respiratory disease, and increased

severity of illness among others. Iatrogenic risk factors are those which are present in the course

of normal ICU care and represent the most amenable to nursing intervention. These include use

of physical restraints, rectal, bladder, epidural, and central venous catheters, excessive noise,

isolation, sleep deprivation, absence of daylight queues, and certain medications (Girard et al.,

2008; Bruno & Warren, 2010).

Of important relevance to this project is the association between medications and the

development of delirium. Several notable studies have indicated that certain drugs, such as

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 4

benzodiazepines and those with anticholinergic activity may attribute a higher risk than others in

the development of ICU delirium. Recently published clinical practice guidelines from the

Society of Critical Care Medicine (SCCM) indicate that while there is conflicting data

surrounding the risk for development of delirium associated with opioid analgesics and propofol,

benzodiazepines haven been consistently found to confer risk versus other drugs used for

sedation (Barr et al., 2013).

Due to the adverse outcomes and evidence suggesting that more harm may come earlier

in the course of delirium, the SCCM Clinical Practice Guidelines for the Management of Pain,

Agitation, and Delirium (PAD) in Adult Patients in the Intensive Care Unit recommend routine

screening for early identification of delirium through the use of one or two validated screening

tools: the Confusion Assessment Method for the ICU (CAM-ICU) or the Intensive Care

Delirium Screening Checklist (ICDSC) (Barr et al., 2013). Without use of a validated screening

tool, assessments are subjective and may miss anywhere from 65-72% of cases of delirium

(Spronk, Riekerk, Hofhuis, & Rommes, 2009). Interestingly, in a study of 1,384 healthcare

professionals conducted in 2001, 86% of practitioners agreed that delirium is an under-diagnosed

syndrome in ICU patients, but only 59% reported actively screening for it in their institution.

Only 19% reported utilization of a validated screening tool (Patel et al., 2009).

Identification of patients with delirium and provision of appropriate preventative

measures for those who are at risk is of utmost importance due to the high morbidity, mortality,

and cost related to development. Not only is the onset of delirium related to higher rates of poor

functional status and decreased quality of life overall after hospitalization, but it also contributes

to higher utilization of long-term care facilities after resolution of critical illness. Recent

evidence has also indicated that the development of delirium is associated with prolonged

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 5

neurocognitive impairment after hospital discharge (Shehabi et al., 2010). While out of hospital

functionality is of utmost importance if patients survive their critical illness, delirium has also

been found to be an independent predictor of mortality and prolonged length of hospital stay and

mechanical ventilation. A study published in 2010 by Shehabi et al. found that the highest

mortality risk from delirium occurred in the early days of onset, with a single day of delirium

contributing to a 70% increased risk of mortality. Each additional day of delirium was associated

with a 100% increase in risk of death or continuation of mechanical respiratory support. Adding

insult to injury, delirium is also associated with increased hospital costs. The average cost of a

single ICU stay is estimated at $20,000-$30,000 per patient, with the development of delirium

relaying a 1.4 fold increase in ICU costs per incident due to increased ventilator time, nursing

and physician time, pharmacy and laboratory costs, and development of hospital-acquired

complications (Milbrandt et al., 2004). This can total up to a $72,000 bill for solely ICU care if

the patient survives their life-threatening illness on top of already devastating functional and

cognitive impairment.

With higher mortality risk conferred earlier in the course, disabling morbidity outcomes,

and potentially devastating attributed cost, it is clear that merely treating delirium once it occurs

will not be sufficient for our patients. The only way to truly avoid these abysmal outcomes is to

prevent the occurrence of ICU delirium. Recommended non-pharmacologic prevention and

treatment options revolve around addressing barriers to senses, such as returning hearing aids,

glasses, and utilizing interpreters; modifying the environment by reducing noise, encouraging

visitation, promoting appropriate sleep/wake signals and restoring day/night queues; and

optimizing ICU care by reducing lines, drains, and interventions, promoting early physical and

occupational therapy, correcting electrolyte and metabolic disturbances, and ensuring hydration

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 6

(Bruno & Warren, 2010). Currently pharmacologic intervention is only indicated for treatment of

identified delirium, and includes reduction of benzodiazepine use, assuring adequate analgesia,

and low-dose antipsychotics. Studied drugs include haloperidol, and the newer ‘atypical’

antipsychotics quetiapine, olanzapine, and zisprasidone (Girard, Pandharipande, & Ely, 2008).

While the above interventions seem straightforward and effective, the recently published

SCCM guidelines recommend only early mobilization as an intervention that may be utilized in

order to reduce the incidence of ICU delirium. The guidelines also indicate that the use of the

sedative dexmedetomidine in place of benzodiazepines may be associated with a lower incidence

of delirium in mechanically ventilated adult patients, but are careful to provide no

recommendation on the use of dexmedetomidine to prevent the occurrence of delirium. Due to

the absence of ‘compelling’ data, SCCM also is careful to make no recommendation regarding

the utilization of a pharmacologic, non-pharmacologic, or combined delirium prevention

protocol in the ICU, but do recommend against utilizing prophylactic antipsychotics due to lack

of data (Barr et al., 2013).

Current Franciscan St. Francis Health policy states that all adult inpatients will be

assessed for the presence of risk factors, which are listed in the policy. In the presence of risk

factors or clinical signs of delirium, the nurse is expected to conduct either the CAM-ICU or

CAM (non-ICU specific) upon admission and at every shift change. These assessments are also

included within the policy. Finally, preventative care strategies are provided within the policy for

direction to collaborate with the physician for treatment orders as warranted. The nurse is

directed through the policy to reduce risk factors through non-pharmacologic interventions

similar to those listed above, with the inclusion of ‘judicious’ administration of high-risk

medications. The policy goes further to recommend utilization of a psychotropic medication as a

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 7

last resort (Franciscan St. Francis Health, 2013). Our current practice in the Adult Intensive Care

Unit (AICU) at Franciscan St. Francis Health is to utilize continuous infusion sedative agents,

including lorazepam and midazolam, for sedation in mechanically ventilated patients, which has

been shown to increase the risk for delirium. In addition, intravenous push lorazepam is utilized

very frequently to calm an agitated patient who is not requiring mechanical ventilation,

sometimes with doses as high as 1 mg every hour. While our policy is very detailed and thorough

regarding non-pharmacologic options, our policy does not provide for nursing-led alterations in

pharmacologic sedative therapy to reduce the risk for transition to delirium.

For this reason, the purpose of this project is to determine whether pharmacologic

prevention strategies through alteration or reduction of sedation agent in addition to non-

pharmacologic prevention strategies could reduce the incidence of delirium in the AICU, and if

so, develop a nurse-driven protocol based on available evidence for use at the bedside.

The Question

For patients in intensive care units (ICU's), does the use of pharmacological management,

versus no pharmacological management, decrease the incidence of ICU delirium?

The Search

The search for relevant articles was started by using the Indiana University PubMed

database to identify those which provided sufficient background information on ICU delirium.

Review articles from reputable peer-reviewed journals and guidelines from professional

organizations were preferred for background information review due to their appraisal and

inclusion of current relevant evidence. Individual primary literature articles were selected from

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 8

evidence compiled within these articles when appropriate for additional background information

and for evidence appraisal.

Research articles to support evidence-based practice on pharmacologic prevention of ICU

delirium were identified through Indiana University access to Ovid and PubMed. Key terms

utilized included a mixture of the following: ICU delirium, pharmacologic prevention,

lorazepam, midazolam, and sedation. A PubMed search was conducted initially followed by

PubMed MESH database search to more specifically pinpoint the topic within PubMed, and

consisted of MESH topics related to above key words.

Articles were included if they were from peer-reviewed reputable medical journals and

were research studies that evaluated the EPB question or provided supporting evidence to

strengthen the recommendation. Additionally, articles were ranked according to the strength of

the study overall, taking into account design, inclusion/exclusion criteria, and sample size. When

initially searching for literature, randomized controlled trials were preferred in selection,

followed by trials not meeting the specifics of this design, followed by meta-analyses/systematic

reviews. Due to the limited quantity of data available, it was anticipated that these would be of

low utility. Case reports were not utilized. Articles specific to the prevention of ICU-related

delirium were reviewed preferentially over those that were post-surgical or medical unit-based in

nature. It is important to note that studies evaluating the discontinuation or preferential use of

certain pharmacologic agents in ICU patients were also included in evaluation of the evidence

since a substantial amount of iatrogenic risk is assumed through drug use in the ICU. Based on

the above criteria and search methods, five articles were included for review into this appraisal of

the evidence.

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 9

Evidence Appraisal

Author, date, title, journal

Level of Evidence

Hypothesis Question or Purpose

Design Sample Size, demographic

Data Collection

Stats/Findings Conclusions Implication

Pandharipande, P., Shintani, A., Peterson, J., Pun, B. T., Wilkinson, G. R., Dittus, R. S., . Ely, E. W. (2006). Lorazepam is an independent risk factor for transitioning into delirium in intensive care unit patients. Anesthesiology, 104(1), 21-26.

Level 4

To test the hypothesis that sedative and analgesic medications are independent risk factors for the transition of patients into delirium

Prospective obser- vational single- cohort study

198 adult, mechanically ventilated critically-ill patients admitted to the medical or coronary ICUs at Vanderbilt University

Daily cognitive status using CAM-ICU and Richmond Agitation Sedation Scale (RASS) Daily doses of fentanyl morphine, lorazepam, propofol, and midazolam Baseline cohort data and presence of other risk factors for delirium

Lorazepam was found to be a dose- dependent risk factor for transition to delirium (OR, 1.2, P= 0.003). Lorazepam daily doses over 20 mg confer a 100% risk of transitioning to delirium. Risk is less with lower doses but still significantly high compared to other agents.

Choice of drug and dose must be weighed to balance sedation needs with risk for negative outcomes, but if lorazepam is needed, the lowest dose possible should be utilized for control of symptoms.

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 10

Author, date, title, journal

Level of Evidence

Hypothesis Question or Purpose

Design Sample Size, demographic

Data Collection

Stats/Findings Conclusions Implication

Riker, R. R., Shehabi, Y., Bokesch, P. M., Ceraso, D., Wisemandle, W., Koura, F., . . . . Rocha, M. G. (2009). Dexmedetomidine vs. midazolam for sedation of critically ill patients, a randomized trial. Journal of the American Medical Association, 301(5), 489-499.

Level 2

To determine if sedation with dexmedetomidine (DEX) would result in improved outcomes over midazolam (MDZ)

Prospective double- blind, randomized controlled trial

366 mechanically ventilated, critically ill medical and surgical ICU patients across 68 hospitals in five countries (United States, Australia, New Zealand, Argentina, Brazil). Of these, 244 patients were enrolled in the DEX group, and 122 patients in the MDZ control group

CAM-ICU and RASS scores, cognitive function Use of supplemental bolus MDZ and fentanyl in addition to study drug Baseline data and other risk factors for delirium Safety data and efficacy data: length of stay, vital signs, time to extubation, adverse events

No difference in sedation or death. DEX group extubated 2 days faster but used more bolus MDZ. 25% decrease in delirium with DEX vs. baseline, also reduced occurrence of delirium vs. MDZ (54% vs. 77%). Shorter duration of delirium in DEX group, but more adverse effects.

Patients in DEX group had less delirium compared to MDZ, indicating potential role in preventing delirium by using alternative agent, even with use of additional low-dose MDZ as needed. DEX may also have role in treatment of delirium.

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 11

Author, date, title, journal

Level of Evidence

Hypothesis Question or Purpose

Design Sample Size, demographic

Data Collection

Stats/Findings Conclusions Implication

Pandharipande, P. P., Pun, B. T., Herr, D. L., Maze, M., Girard, T. D., Miller, R. R., . . . . . . . Ely, E. W. (2007). Effect of sedation with dexmedetomidine vs. lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. Journal of the American Medical Association 298(22), 2644- 2653.

Level 2

To determine if dexmedetomidine (DEX) reduces the duration of delirium and coma compared with lorazepam (LZ)

Prospective double- blind, randomized controlled trial

103 adult medical and surgical ICU patients requiring mechanical ventilation for longer than 24 hours at two hospitals were enrolled. 52 patients were randomized to the DEX group, 51 patients were randomized to the LZ control group.

CAM-ICU and RASS for 12 days Use and dose of propofol and fentanyl in addition to study drug Baseline data and other risk factors for delirium Safety, cost, and efficacy data

DEX group had 4 more days without delirium or coma vs. LZ, but no difference in occurrence or duration of delirium alone. No mortality difference between groups, but sedation with DEX more effective. Patients in DEX group received substantially more fentanyl (575 mcg/day vs. 150 mcg/day).

DEX reduced the rate of over- sedation, even with high-dose concurrent fentanyl infusion. No impact on delirium was observed.

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 12

Author, date, title, journal

Level of Evidence

Hypothesis Question or Purpose

Design Sample Size, demographic

Data Collection

Stats/Findings Conclusions Implication

Pandharipande, P. P., Sanders, R. D., Girard, T. D., McGrane, S., Thompson, J. L., Shintani, A. K., . . Ely, E. W. (2010). Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial. Critical Care, 14(R38): 1-12.

Level 2

To determine if outcomes in septic vs. non- septic patients were different when dexmedetomidine (DEX) was used for sedation vs. lorazepam (LZ)

A priori subgroup analysis of previous prospective double- blind, randomized controlled trial

103 adult medical and surgical ICU patients requiring mechanical ventilation for longer than 24 hours at two hospitals were enrolled. 63 patients had sepsis: 31 in DEX group and 32 in LZ group. 40 patients did not have sepsis: 21 in the DEX group and 19 in LZ group.

CAM-ICU and RASS for 12 days Use and dose of propofol and fentanyl in addition to study drug Baseline data and other risk factors for delirium Safety, cost, and efficacy data Antibiotic and treatment data for admitting condition

Septic DEX patients had more effective sedation, less delirium and ventilator-free days, with lower mortality vs. LZ. Patients on DEX overall had 70% lower odds of being delirious versus LZ. More fentanyl received in all DEX groups vs. LZ, no safety issues.

DEX may be more effective at reducing delirium and ventilator time in patients with sepsis compared to LZ and in those without sepsis. It also is associated with lower odds of transition to delirium vs. LZ and may be useful as a preventative measure even when high dose fentanyl is used concurrently.

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 13

Author, date, title, journal

Level of Evidence

Hypothesis Question or Purpose

Design Sample Size, demographic

Data Collection

Stats/Findings Conclusions Implication

Skrobik, Y., Ahern, S., Leblanc, M., Marquis, F., Awissi, D. K., Kavanagh, B. P. (2010). Protocolized intensive care unit management of analgesia, sedation, and delirium improves analgesia and subsyndromal delirium rates. Anesthesia & Analgesia, 111(2), 451-463.

Level 3

To determine whether implementation of a combined pharmacologic and non- pharmacologic pain, agitation, and delirium (PAD) protocol would affect ICU outcomes or incidence of delirium.

Prospective pre- and post- interventio n, obser- vational controlled trial

1,214 adult surgical and medical ICU patients at a single hospital were enrolled. 610 patients were in the pre-protocol group and 604 in the post- protocol group.

Pain, agitation (RASS), and delirium (ICDSC) assessments every 8-hour shift during the ICU stay Total doses of all drugs used and type of protocol, and prescription patterns Baseline data and other risk factors for delirium

Post- intervention group was sicker, but improved pain control with 78% lower opioid doses, 52% lower BZD doses w/ similar sedation, and 25% less sybsyndromal delirium. Rates of delirium were similar in both groups. Oversedation, ventilator days, length of stay and mortality also significantly reduced in post- group vs. pre- group

Implementati on of a PAD protocol significantly improves outcomes while maintaining or improving levels of sedation and analgesia. Benefit on delirium not as clear, but benefit likely outweighs risks.

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 14

Summary of Literature Review

Review of the existing literature provides a few important considerations. Firstly, that the

quantity of data available is very limited and generally confined to small studies, results of which

are conflicting on certain points. Secondly, the study of delirium occurrence and potential

pharmacological prevention options is apparently a very specialized field of study, as the same

authors appear frequently and almost continuously throughout each article that was reviewed. It

is important to note this fact as the frequency of publication indicates that several of these

authors have a strong passion for this topic, which may influence reporting of their findings.

Finally, there appear to be several approaches to the pharmacologic prevention of ICU delirium;

however, it was decided between this writer and the preceptor, Nurse Durham, to explore those

interventions that are more appropriately influenced by nursing practice and could be optimized

at our institution.

As previously mentioned, there were some conflicting outcomes that were identified

upon review of the literature. While all studies utilized occurrence of delirium as one of the

intended endpoints, the information gained from these articles was strikingly different. Each

study attempted to reduce the incidence of delirium by utilizing a differing pharmacologic

approach, with sometimes conflicting results. For example, two of the articles investigated the

use of dexmedetomidine as a sedative in mechanically ventilated ICU patients versus standard-

care continuous infusion benzodiazepine. While the studies were similar in terms of design,

Riker et al. identified that dexmedetomidine utilized as a sedative agent was superior to

midazolam in preventing delirium (2009), while the MENDS trial identified that

dexmedetomidine had no substantial effect on rates of ICU delirium versus sedation with

lorazepam (Pandharipande et al., 2007). Conversely, dexmedetomidine was shown to be more

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 15

effective in preventing delirium versus lorazepam for patients with sepsis in a subgroup analysis

of the same study (Pandharipande et al., 2010). The last two trials were very different in

approach from those previously described in this review and were included to determine whether

attempts to minimize benzodiazepine use within the ICU by either reducing total dose exposure

or by electing an alternative sedative agent via a protocol would in fact be effective in preventing

delirium. The trial by Pandharipande et al. conducted in 2006 demonstrated that lorazepam use

was associated with the conversion to ICU delirium in a dose-dependent fashion. Results indicate

that if adequate measures are taken to dramatically reduce the utilization of high-dose

benzodiazepines in the ICU, more delirium should be prevented. This theory was examined in

the final study, which evaluated implementation of a pain, agitation, and delirium (PAD)

protocol, in which the nurse could adjust, alter, and titrate pharmacologic therapy to obtain

desired goals. While no difference was found in the incidence of ICDSC-proven delirium,

subsyndromal delirium rates were reduced dramatically (Skrobik et al., 2010).

It is fairly evident from the above summary that while all of the studies themselves may

have had vastly differing designs, overall similar findings were identified. If one chooses the

theme of reduced benzodiazepine use as a pharmacologic approach to preventing ICU delirium,

for example, four of the five studies indicate at least partial benefit. Three of the four studies

identified a significant reduction in ICU delirium when either dexmedetomidine was utilized

over a benzodiazepine or when less benzodiazepine was utilized overall (Riker et al., 2009;

Pandharipande et al., 2006; Pandharipande et al., 2010), and the fourth study found a significant

reduction in subsyndromal delirium rates with implementation of a protocol designed to reduce

benzodiazepine use, among other standards of care (Skrobik et al., 2010). Interestingly, even the

MENDS trial, which showed no benefit in utilization of an alternative agent against continuous

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 16

infusion lorazepam, seems to corroborate the finding that lorazepam is an independent risk-factor

for development of ICU delirium. The trial by Pandharipande et al. (2006) demonstrated that the

risk for delirium increased dramatically as exposure to lorazepam increased, with 20 mg daily

doses conferring a certainty of development. Although no difference was found in the

development of delirium, the MENDS trial data, as discussed above, seems to corroborate this

finding as rates of delirium were very high (82%) in the lorazepam group, which utilized high-

dose continuous infusion. While the incidence was unexpectedly similar in the dexmedetomidine

group in the MENDS trial (79%), this could be explained by a higher utilization of fentanyl and

propofol for additional sedation in this group overall (Pandharipande et al., 2007).

The trials that were selected, while varied in prospective study design, were of good

quality overall. The least effective study design was that of the subgroup analysis MENDS trial,

which examined the incidence of delirium between septic and non-septic patients in those

sedated with lorazepam versus dexmedetomidine. Because this was designed as a subgroup

analysis, it was not the primary outcome of the study, and was not truly adequately powered or

designed for as an outcome (Pandharipande et al., 2010). Additionally, the study by

Pandharipande et al. conducted in 2006 was of only a single cohort design with no control group

with which to compare findings. Although the study is overall designed well, this is a limitation.

The other three studies were all controlled study designs, with two including randomization to

further strengthen results (Riker et al., 2009; Pandharipande et al., 2007; Skrobik et al., 2010).

Treatment effects were positive in general on prevention of delirium through

pharmacological reduction of benzodiazepine utilization. Additionally, it is important to note that

other beneficial outcomes were identified through this intervention, even in the studies that were

somewhat lacking in strong benefit in the prevention of ICU delirium. A clear example is the

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 17

study by Skrobik et al. (2010) which examined the impact of a protocolized PAD protocol

among 1,214 adult surgical and medical ICU patients. While the benefits were not entirely clear

as they related to delirium itself, utilization of a protocolized approach to PAD significantly

decreased mortality, reduced ICU length of stay and ventilator time, improved pain scores with

drastically lower opioid doses, and maintained a similar level of sedation while using half as

much benzodiazepine due to alternative agent selection or bolus injection method.

It is clear from review of this literature that evidence is limited. With this in mind, the

small amount of evidence that is available indicates that minimization of benzodiazepine dose

through utilization of an alternative agent or bolus dosing on an as-needed bases to meet

therapeutic sedation goals may be effective pharmacologic strategies by which to prevent ICU

delirium. An interesting an unexpected finding during this review is the potential impact of this

strategy on other outcomes, including mortality, length of stay, ventilator time, and incidence of

oversedation. Even if no impact on delirium through this method is noted, it delivers a

substantial benefit in other major ICU outcomes; therefore benefit most certainly outweighs

risks.

Proposal for Practice Change

The AICU at Franciscan St. Francis Health utilizes several different sedation strategies in

our mechanically ventilated critically ill patients, including high-dose continuous infusion

lorazepam, which puts our patients at unnecessary risk for transition into delirium. Based on this,

the lack of guidance on pharmacologic prevention of delirium in St. Francis policy, as well as

literature review, it was elected for this project to change practice project via implementation of a

nursing driven protocol whereby a patient’s Registered Nurse (RN) would be able to alter the

sedative agent from lorazepam to dexmedetomidine unless the patient had either hemodynamic

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 18

instability or was experiencing alcohol withdrawal. In these cases, the RN would transition the

patient from high-dose continuous infusion lorazepam to bolus dosing every one hour as needed

to maintain the desired sedation goal utilizing the Riker Sedation Assessment Scale (SAS). The

objective of this protocol is to prevent ICU delirium through altering of pharmacologic sedation

therapy. The project question was initially approved by course instructor, which was followed by

a meeting with the project preceptor, Kim Durham, RN, BSN, CCRN. At this time the

background data, evidence, and proposed changed in practice were reviewed and approval was

obtained from Nurse Durham to undertake this initiative.

Our unit has traditionally been fairly resistant to change. While our patients are unable to

voice their preference for delivery of sedative therapy due to mechanical ventilation, our fellow

nurses and physicians are somewhat of a different story. In general, our critical care physician

group will tend to be hesitant when it comes to implementing a new nursing-driven protocol, but

will be convinced with an impressive quantity of data and well thought-out plan. Since the data

in this arena is somewhat limited, persuading this group may be challenging without the right

approach. More intimidating, however, is approaching the change from a nursing process

standpoint, as most of our nurses are seasoned veterans who would prefer to take care of the

patient in the least-time consuming, most effective manner. It is safe to say that they prefer

taking care of patients on continuous infusion lorazepam drips due to the peacefulness the drug

imparts on the patient. Convincing them to alter their practice to change drugs to

dexmedetomidine, which they view as less effective, will be difficult. More intimidating is the

implementation of a new process change that requires the RN to enter the patient’s room every

30 minutes to assess SAS and administer bolus lorazepam. Again, we are confident that we can

onboard these key stakeholders with the right approach, which will likely include education,

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 19

multidisciplinary support, incentives, and accountability. Resources available for implementing

the change include leaders on our unit, including our manager, clinical educator, and clinical

nurse specialist, as well as multidisciplinary committees, our online learning system, and

organizational support.

In order to obtain support from our fellow RN’s and physicians regarding this initiative, it

is essential that we create a Change Team. Members of the team from a nursing perspective will

include this writer, the preceptor, Kim Durham, RN, BSN, CCRN, who is also a unit Patient

Care Coordinator (PCC), the other PCCs on the unit, and our unit manager, clinical educator, and

clinical nurse specialist. In addition two nurses who have a strong leadership presence and

clinical skills will be selected from each shift to act as a role model for the other nurses on the

unit. Interdisciplinary involvement is also essential. The Director of Medicine will also be

included in attempt to influence the intensive care unit physicians and promote change within the

group. The last practitioner who must be involved is the clinical pharmacist for the AICU.

Pharmacists are uniquely positioned with one foot inside the nursing world of drug

administration and the other foot inside the physician world of drug prescribing. A pharmacist

will serve to act as the drug expert for the protocol while also bridging the gap between nursing

and physician drug utilization work flow.

With involvement of multiple professions, it is also critical that collaboration is achieved.

Differing viewpoints and perceptions can cause rifts between the practices, so it is important that

mutual respect is maintained. Patients will be treated with dignity, confidentiality, and respect,

regardless of religion, culture, or values. The same will be required of all team members. All

ethical issues will be discussed with the team, which will decide as a group and utilize that

decision as the voice of the group to convey messages. It is also essential within the group that

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 20

roles are clearly delineated and that each individual is able to contribute within the defined limits

of their scope of practice. This will be achieved by voting on roles and responsibilities during the

first meeting, and discussing specific assignments related to each role both at the beginning and

at the end of the meeting. Opinions from members regarding their specific field of practice will

be considered ‘expert opinions’ and will be treated as such. Communication is also of utmost

importance, and therefore discussions will be productive and opinions will be encouraged and

respectfully discussed. It is preferred to meet in person, but when required, teleconferences, and

electronic mail will also suffice. Meeting minutes will be distributed to all members of the team

at the completion of each gathering. As I am personally invested in this project, I plan to

incorporate my own personal leadership style of directing and challenging other team members

to think outside of normal practice standards. I will take time out of each meeting for the group

to weigh in on ways to improve implementation of the protocol or increase efficiency. I have

excellent communication and reasoning skills, and will also be an asset to the team in times of

conflict and indecisiveness.

In order to implement this protocol, the team will first determine its contents. After

agreement is reached by the team, the protocol will be presented to the hospital’s Pharmacy and

Therapeutics Committee and Nursing Executive Council for approval. When approval is

achieved, all staff nurses will be required to attend mandatory staff meetings for introduction of

this protocol. After the meetings, the nurses will be required to view a mandatory online learning

module regarding the protocol. This will include detailed information about how the protocol

will be utilized, the patient populations in which it should be used, and instructions for use. At

the completion of the learning module will be a test consisting of 20 questions regarding

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 21

appropriate use of the protocol. Passing grade will be set at 100%. The protocol will be

implemented by the unit nurses on go-live date, which at this time is set for 10/1/2014.

Objectives Method/Plan Responsibility Completion

Date Measurable Outcomes

Decrease benzodiazepine use by 50%

Develop and implement nursing-led protocol for automatic adjustment of ICU sedation and provide nursing and physician education

Unit manger, Unit educator, Unit CNS, Unit leaders, Pharmacy, Physicians

4/11/2015 Decreased lorazepam total daily doses and drug expenditures

Decrease incidence of ICU delirium by 25%

Utilize nursing- led protocol for automatic adjustment of pharmacologic risk factors

AICU staff 10/01/2015 Decreased quantity of positive CAM- ICU scores in RN assessment

Evaluation Plan

Evaluation of the practice change will begin immediately on implementation date and

continue as needed as long as the protocol continues to be active as determined by hospital

executive committees. Nurses will be informally quizzed daily and patient charts will be spot-

checked daily for the first two weeks to ensure proper use of the protocol. Once the protocol has

been utilized appropriately for at least 14 consecutive days, the protocol will be deemed as

satisfactorily implemented and evaluation of outcomes associated with the practice change will

begin. Success of the initiative will be measured with the assistance of nursing, pharmacy, and

physician personnel utilizing the methods described in the following table.

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 22

Measurable Outcomes

Method and Tools for Measuring

Responsibility Timelines

Decreased lorazepam total daily doses and drug expenditures

Retrospective chart review of pre- and post- implementation medication administration data including pharmacy purchasing information

Team Pharmacist Begin collecting retrospective data at a look-back of six months prior to implementation of protocol. Collect post- implementation data at 6 months, 2 years, and 5 years

Decreased quantity of positive CAM-ICU scores in RN assessment

Retrospective chart review of pre- and post- implementation chart documentation data

Nursing Begin collecting retrospective data at a look-back of six months prior to implementation of protocol. Collect post- implementation data at 6 months, 2 years, and 5 years

Resources

The primary resources required within the first year of the practice change will be

primarily people and time. It will be of utmost importance that our fellow staff members of the

AICU continue to uphold and utilize the new protocol, even though it might be more time

consuming to assess sedation level more frequently for administration of lorazepam bolus doses,

for example. In addition, a substantial amount of time and the appropriate personnel will be

essential to conduct ongoing reviews of whether the protocol is being utilized effectively and if

as a result, positive outcomes are occurring. With the potential for 30 patients in the AICU on

mechanical ventilation on the protocol at any given time, the data collection will be substantial.

Costs will be primarily related to the use of staff. Each project team meeting will cost

approximately $475 in labor expenses. Therefore, it is imperative that meetings are utilized only

when required. It is estimated that three meetings, or $1,425 will be required in order to develop

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 23

the protocol. Protocol education will require each of the 60 unit staff nurses to attend a

mandatory staff meeting, with an associated online learning module. Assuming each of these is

an hour in duration, this will cost $3,000 in labor. Evaluation of the protocol is to occur via chart

review on initiation, at six months, two years, and at five years post-initiation. Eight hours of

labor for both a nurse and a pharmacist on each of these occasions will total to approximately

$4,800. For this project, the total labor cost is estimated to be approximately $9,225 for

implementation and evaluation.

The cost of this project will be offset by savings related to reduced lorazepam expenses

and, more importantly, savings related to prevention of ICU delirium. As described previously

by Milbrandt et al., (2004) the development of delirium relays a 1.4 fold increase in total ICU

costs per incident. If this is estimated conservatively at approximately $28,000 per delirious

patient, and the protocol is successful in preventing 25% of cases, the hospital could potentially

save $700,000 for every 100 mechanically ventilated patients, assuming a previous delirium rate

of 80%. As our ICU sees upwards of 360 patients requiring mechanical ventilation annually, this

cost savings would be dramatic.

Conclusion

ICU delirium is a clear public health problem that can affect up to 80% of patients in the

critical care unit, and is associated with substantial costs as well as dramatically increased

morbidity and mortality. Since neither treatment nor prevention strategies have been previously

well defined, this project was conducted to determine whether a pharmacologic prevention

strategy could decrease the occurrence of delirium in ICU patients. While studies related to this

particular topic are somewhat lacking, evidence exists indicating that alteration of pharmacologic

sedation therapy could potentially prevent the occurrence of delirium in mechanically ventilated

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 24

patients. Practice change is needed in the AICU at Franciscan St. Francis Health, which would be

most optimally influenced by implementation of a nurse-driven protocol allowing the nurse to

alter pharmacologic risk factors for ICU delirium and thus potentially prevent onset. This change

in practice could contribute not only to substantial cost savings for the patient and hospital, but

also prevent mortality. As nurses, our professional code of ethics charges us to do no harm. This

project demonstrates that we have the ability to reduce the risk for harm caused within normal

daily practice, and so it is imperative that we embrace this proposed change and move forward as

advocates for our patients.

PHARMACOLOGIC PREVENTION OF ICU DELIRIUM 25

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