Safety and Efficacy of Intramuscular Olanzapine Alone or in Combination with

Benzodiazepines for the Management of Acute Agitation in the Emergency Department Karen Lai, Pharm.D., Gillian Pineda, Pharm.D., BCPS and Leonard Valdez, Jr., Pharm.D., BCPS

Community Regional Medical Center – Fresno, California

Acutely agitated patients in the emergency

department (ED) have been conventionally

treated with first-generation antipsychotics alone

or in combination with benzodiazepines (BZDs).1

Second-generation antipsychotics have also

become increasingly used in the acute setting for

management of agitation.2

Concomitant use of intramuscular (IM)

olanzapine and parenteral benzodiazepines may

result in excessive sedation and cardiorespiratory

depression,3,4,5,6 and is not recommended by the

U.S. Food and Drug Administration.7

All authors of this presentation have nothing to disclose

concerning possible financial or personal relationships with

commercial entities that may have a direct or indirect interest

in the subject matter of this presentation.

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Study Design

Retrospective chart review

All patients who received IM

olanzapine in the ED

October 1, 2011 through July 31, 2013

Data Collection

Demographics

Past medical history

Chief complaints/diagnosis

Vital signs and oxygen saturation

History of alcohol or substance abuse,

and serum alcohol level at admission

Dose/sequence/frequency/timing of all

antipsychotics, BZDs, anticholinergics

and CNS depressants administered

Disposition of patient

Outcome Measures

Safety

• Cardiorespiratory depression

• Excessive sedation

Efficacy

• Need for physical restraints

• Total amount of olanzapine given

• Need for additional antipsychotics

or agents with sedative properties

Evaluate the safety of IM olanzapine with or

without BZDs by means of drug effects on vital

signs, decrease in oxygen saturation from

patients’ baseline and mortality

Assess for drug efficacy with respect to adequate

agitation reduction measured by the need for

additional medications and/or physical restraint

within 2 hours of treatment initiation

This study proposal was submitted to and approved by the

Institutional Review Board at Community Regional Medical Center.

All data will be recorded without patient specific identifiers and

maintained in a confidential manner to protect patient privacy.

Patient Enrollment and Exclusion

Preliminary Results

Ht – height, Wt – weight, HTN – hypertension, SBP – systolic blood pressure, DBP – diastolic blood

pressure, HR – heart rate, RR – respiratory rate, O2Sat – oxygen saturation

Complete data collection and analysis

Revise treatment recommendation on existing

order set for the management of acute agitation,

if applicable

Perform cost-savings analysis

Preliminary data suggests that when compared

to intramuscular olanzapine alone, the

combination of intramuscular olanzapine with

benzodiazepines has less adverse effects on

blood pressure and is less efficacious in the

treatment of acute agitation in the emergency

department.

1. Zimbroff DL. Pharmacological Control of Acute Agitation – Focus on

Intramuscular Preparations. CNS Drugs 2008; 22(3): 199-212.

2. Allen MH, Currier GW, Carpenter D, et al. The expert consensus guideline

series. Treatment of behavioral emergencies 2005. J Psychiatr Pract. 2005;

11(1): 4-112.

3. Olanzapine package insert. Eli Lilly, Revised 06/2011.

4. Wilson MP, MacDonald K, Vilke GM, Feifel D. Potential complications of

combining intramuscular olanzapine with benzodiazepines in emergency

department patients. J of Emer Med 2012; 43(5): 889-896.

5. MacDonald K, Wilson M, Minassian A, et al. A naturalistic study of

intramuscular haloperidol versus intramuscular olanzapine for the

management of acute agitation. J Clin Psychopharmacol 2012; 32: 317-322.

6. Eli Lilly and Company Limited. Letter to healthcare professionals.

Basingstoke, Hampshire, UK: Eli Lilly and Company Limited, 2004 Sep.

7. Zyprexa Safety Information. MedWatch The FDA Safety Information and

Adverse Event Report Program. Updated 6/15/2010.

BACKGROUND

OBJECTIVES

METHODOLOGY RESULTS CONCLUSION

FUTURE DIRECTION

REFERENCES

Age Male Ht

(in)

Wt

(kg)

BMI SBP DBP HR RR O2

Sat

HTN

History

Olanzapine

Dose, Average

OB 43.4 50% 66.8 81 28.5 140.5 88.2 93.4 19.4 98 70% 8mg

O 39.3 70% 67.4 73.8 25 134.8 84.4 83.1 17.4 98.2 50% 8.5mg

Table 1. Patients’ baseline characteristics

Time Elapsed Since Drug

Administration (minutes) SBP DBP HR RR O2 Sat Need for

Additional Drug

Need for

Restraint

OB 120.2 -6.2 -5.9 -12 0 -0.11 40% 40%

O 158.7 -21 -18.8 -11.3 -0.2 +0.3 0% 20%

Table 2. Changes in monitoring parameters after drug administration

Patient Specific Parameters Which Compel the Use of Voriconazole in the Treatment

of Coccidioidomycosis Over Traditional Antifungal Therapy

Tamar K. Lawful, Pharm.D., Luma Munjy, Pharm.D., Justin Petrovic, Pharm.D.,

Samia Sheikh, Pharm.D., and Marisa N. Méndez, Pharm.D., BCPS

Community Regional Medical Center – Fresno, California

BACKGROUND

Coccidioidomycosis is endemic in the Central Valley of

California. California reported a total of 4,094 cases in

2012.1 During 2012, the top three counties with the

highest number of reported cases were Kern (1859),

Fresno (475), and Los Angeles (321) counties.1

Fluconazole, itraconazole, and amphotericin B are the

traditional antifungal treatment options for

coccidioidomycosis; however, patients may not clinically

respond to these agents.2

The disease process can manifest as a self-limited flu-

like process or fulminant respiratory failure.

Approximately 1% of all coccidioidomycosis infections

disseminate, affecting the bones, joints, skin, central

nervous system, or organs.2

Voriconazole has shown favorable effects in patients

with refractory coccidioidomycosis. Early initiation of

voriconazole therapy could prevent disease

progression, avoid or decrease hospital stay, and

decrease healthcare costs.3,4

OBJECTIVE

CONCLUSIONS

REFERENCES

METHODOLOGY

1. California Department of Public Health, Infectious Diseases Branch, Surveillance and

Statistics Section. (2012) Coccidiodomycosis Yearly Summary Report 2012. Retrieved

August 7, 2013, from http://www.cdph.ca.gov/programs/sss/Documents/COCCI-

UPDATED2012YEARLY.pdf

2. Seitz AE, Prevots R, and Holland SM. Hospitalizations Associated with Disseminated

Coccidioidomycosis, Arizona and California, USA. Emerging Infectious Diseases. 2012;

18 (9):1476-1479.

3. Dodds-Ashley ES, Lewis R, Lewis JS, Martin, C, and Andes D. Pharmacology of

systemic antifungal agents. Clinical Infectious Disease. 2006; 43: S28–39.

4. Kim MM, Kusne HR, Seville MT, and Blair JE. Treatment of Refractory

Coccidioidomycosis with Voriconazole or Posaconazole. Clinical Infectious

Disease.2011; 53:1060-1066.

Study Design

Observational retrospective study of patients

with coccidioidomycosis who were hospitalized

between 2005 and 2013.

Data Collection

Patient characteristics, antifungal therapy, and

disease course data were collected from

electronic and paper medical records.

Outcome Measures

RESULTS

The patient population consisted of 13 patients ages 18-

68 years. The majority of the patients were of Latino

descent (54%). Preliminary results reflect a higher

occurrence of disease progression in patients with an

occupation in agriculture (23%) and patients on

concurrent corticosteroid therapy (23%).

Data collection will be continued and results assessed

to identify additional characteristics that could indicate

earlier initiation of voriconazole therapy.

FUTURE DIRECTION

All authors of this presentation have nothing to disclose concerning

possible financial or personal relationships with commercial entities that

may have a direct or indirect interest in the subject matter of this

presentation.

Continued research is needed to distinguish common

characteristics in patients non-responsive to traditional

therapy for coccidioidomycosis infections. These

characteristics may predict the need for voriconazole

earlier in the course of coccidioidomycosis treatment,

preventing disease progression.

7-046

Identify common characteristics in patients with

coccidioidomycosis non-responsive to traditional

therapy that may contribute to treatment failure.

This study proposal was submitted and approved by the Institutional

Review Board at Community Regional Medical Center. All data will

be recorded without patient specific identifiers and maintained in a

confidential manner to protect patient privacy.

Inclusion Criteria

Diagnosis of coccidioidomycosis infection

Voriconazole therapy initiated after traditional

antifungal treatment failure

18 years of age and older

Exclusion Criteria

Pregnancy

Parameters for disease regression

Symptoms Anticipated effect

Fever/Chills Resolution

Rash Resolution

Weight Increased or maintained

Cough Resolution

Pain Decreased or maintained

Radiographic studies Lesions/no change/stable

Serologic tests Decreased antibodies/no

change

Patient Population

Female Male

Number of patients (n) 6 7

Age range (years) 21-68 18-57

69% (n = 9) 8% (n = 1)

23% (n = 3)

Risk Factors for Disease Progression

Unknown HIV Corticosteroid therapy

0

1

2

3

4

5

6

7

White African American

Latino Other

1

3

7

2

Pa

tie

nts

(n

)

Ethnicity of Study Subjects

0 1 2 3 4

Office/Academia

Food /Service Industry

Construction

Correctional Facility

Agriculture

Unknown

1

2

1

2

3

4

Patients (n)

Source of Coccidioidomycosis Exposure

BACKGROUND

Broad spectrum beta-lactam antibiotics, such as

cefepime and meropenem, are frequently utilized

in the intensive care unit (ICU) setting.

Compared to traditional intermittent infusion,

extended infusion administration of beta-lactam

antibiotics has been shown to improve outcomes,

such as decreased mortality rate and length of

stay (LOS),1,2,3,4 mainly in the general medicine

population.

Extended infusion administration has not been

extensively studied in the trauma or burn ICU

population, a unique subset of patients who are

often in a hypermetabolic state.5

OBJECTIVES

CONCLUSIONS

REFERENCES

METHODOLOGY

RESULTS

FUTURE DIRECTION

All authors of this presentation have nothing to disclose concerning possible

financial or personal relationships with commercial entities that may have a

direct or indirect interest in the subject matter of this presentation.

Efficacy of Extended Infusion Cefepime and Meropenem in Trauma and Burn Intensive

Care Unit Patients at a Level One Trauma and Burn Center Christina J. Wong, Pharm.D., Melissa A. Reger, Pharm.D., BCPS, Marisa N. Méndez, Pharm.D., BCPS and Ann W. Vu, Pharm.D., BCPS

Community Regional Medical Center – Fresno, California

This study proposal was submitted to and approved by the Institutional

Review Board at Community Regional Medical Center. All data will be

recorded without patient specific identifiers and maintained in a confidential

manner to protect patient privacy,

Study Design

Retrospective chart review

Pre-implementation: Oct.1, 2011 – Jan. 24, 2012

Post-implementation: Oct.1, 2012 – Jan. 24, 2013

Inclusion Criteria

Patients admitted to trauma or burn ICU service

during study periods

Receipt of cefepime or meropenem for a minimum of

5 consecutive days

Exclusion Criteria

Less than 18 years of age

Receiving concomitant beta-lactam antibiotics

Insufficient microbiologic data

Defined as negative cultures or absence of cultures

Organism not sensitive to cefepime or meropenem

Incarcerated patients

Pregnant patients

Data Collection

Antibiotic selection and history

Microbiologic culture and sensitivities data

Injury Severity Score and injury site

Total body surface area burn

Length of mechanical ventilation (if applicable)

Concomitant infections

Infection recurrence

Hospital/ICU LOS

All-cause mortality through hospital discharge

Total cost of therapy

Acquisition cost of antibiotic

Hospital/ICU LOS

Complete data collection and statistical analysis

Conduct subgroup analysis comparing outcomes

in trauma versus burn patients

Submit Institutional Review Board Research

Study Modification Form to extend study period

1. Bauer KA, West JE, O’Brien JM, et al. Extended-Infusion Cefepime

Reduces Mortality in Patients with Pseudomonas aeruginosa Infections.

Antimicrobial Agents and Chemotherapy 2013; 57(7):2907-912.

2. Falagas ME, Tansarli GS, Ikawa K, et al. Clinical Outcomes With Extended

or Continuous Versus Short-term Intravenous Infusion of Carbapenems

and Piperacillin/Tazobactam: A Systematic Review and Meta-analysis.

Clinical Infectious Diseases 2013; 56(2):272-82.

3. Yost RJ and Cappelletty DM. The Retrospective Cohort of Extended-

Infusion Piperacillin-Tazobactam (RECEIPT) Study: A Multicenter Study.

Pharmacotherapy 2011; 31(8):767-75.

4. Wang D. Experience with extended-infusion meropenem in the

management of ventilator-associated pneumonia due to multi-drug

resistant Acinetobacter baumannii. Int J Antimicrob Agents 2009; 33:290-1.

5. Weinbren MJ. Pharmacokinetics of antibiotics in burn patients. Journal of

Antimicrobial Chemotherapy 1999; 44:319-27.

Compare efficacy of cefepime and meropenem in

trauma and burn ICU patients before and after

the implementation of a hospital-wide “Automatic

Substitution to Extended Infusion for Select Beta-

lactams” protocol

Evaluate the effect of extended infusion regimens

on rates of infection recurrence, all-cause

mortality, hospital LOS, and ICU LOS

Determine whether the extended infusion

regimen provides cost-savings

Preliminary Results

Pre-implementation:

103 trauma charts reviewed

8 patients met inclusion criteria

Post-implementation:

121 trauma charts reviewed

8 patients met inclusion criteria

Outcome Measures

Preliminary data suggests that, compared to

traditional intermittent infusion, extended infusion

administration of cefepime in the trauma ICU

population may result in a greater rate of infection

recurrence.

The current study period is insufficient to conduct

analysis on an adequate number of subjects to

determine the desired outcome measures. Parameter Pre-

implementation

Post-

implementation

Age (years) 50.0 47.9

Male (%) 7 (87.5) 8 (100)

Length of mechanical

ventilation (days)

19.4 30.4

Primary injury site (%)

Head/Neck 3 (37.5) 3 (37.5)

Face 0 (0) 0 (0)

Chest 3 (37.5) 2 (25)

Abdomen/Pelvis 1 (12.5) 2 (25)

Extremities 1 (12.5) 1 (12.5)

External 0 (0) 0 (0)

Antibiotic (%)

Cefepime 8 (100) 8 (100)

Meropenem 0 (0) 0 (0)

Parameter Pre-

implementation

Post-

implementation

Infection recurrence (%) 0 (0) 2 (25)

Pneumonia 0 (0) 2 (25)

Hospital LOS (days) 31.0 35.9

ICU LOS (days) 19.8 28.8

All-cause mortality (%) 0 (0) 0 (0)

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