Sepsis in the NICU and Interventions to Improve Care Joseph El Khoury, MD

Children’s Hospital of Richmond at VCU

Virginia Neonatal Perinatal Collaborative Meeting

May 12th, 2017

Significance of Sepsis in the NICU

Neonatal sepsis, especially hospital acquired sepsis, is a major healthcare concern High mortality

High morbidity

Extended length of stay

A lot of stress on Neonatologists/NNP/RNs

Early-Onset Neonatal Sepsis: A Continuing Problem in Need of Novel Prevention Strategies. Stoll, B. J. PEDIATRICS, 12/01/2016, Vol.138(6)

Very Low Birth Weight a Risk Factor

Rates of infection, morbidity and mortality continue to be highest among preterm infants Especially very low birth weight infants (1)

Virtually all very low birthweight (VLBW) and roughly half of term infants require intensive care for respiratory support and/or blood pressure support (2)

1. Stoll et al. Early-Onset Neonatal Sepsis: A Continuing Problem in Need of Novel Prevention Strategies. PEDIATRICS, 12/01/2016, Vol.138(6) 2. Stoll BJ, Hansen NI, Sánchez PJ, et al: Early onset neonatal sepsis: The burden of group B streptococcal and E. coli disease continues. Pediatrics 127:817-826, 2011

Ages 1-3 days of life (n=104,676) Early onset sepsis 1%

Early onset sepsis mortality 25.9% (vs 11.3%)

Ages 4-120 days of life (n=99,796) Late onset sepsis 12.2%

Late onset mortality 15.1% (vs 8.5%)

Mortality Rate from Sepsis is high

Hornik CP. Mortality: Early Onset Sepsis (EOS) & Late Onset Sepsis (LOS). Early Human Dev 2012;88(S2):s69. r Very Low Birth Weight ( < 1500 grams) Infants

Challenges with Neonates

Not all newborns exhibit symptoms when septic

Premature and ill neonates often present with nonspecific and subtle signs that delay identification and early treatment Experience is key

One study of infants born ≥37 weeks found bacteremia in 0.5% of evaluated asymptomatic infants versus 3.2% of evaluated symptomatic infants(1)

1. Johnson CE, Whitwell JK, Pethe K, et al: Term newborns who are at risk for sepsis: Are lumbar punctures necessary? Pediatrics 99:e10-e14, 1997

Underdeveloped Immune System

Neonates have a compromised immune system

Neutrophils in neonates: Are less able to move into tissue

Have deficient killing capacity

Are quickly depleted in critically ill neonates Are not replenished quickly enough due to immature bone marrow

Neonates have decreased levels of immunoglobulins

To Treat or not to Treat

The majority of Neonatologists would vote “treat”

Current practices are to “shoot and ask questions later” High suspicion for sepsis

Evaluate any signs and symptoms that deviate from baseline

Low threshold for obtaining cultures and starting antibiotics

Also generally agreed upon is that early treatment is better and safer than late treatment

Challenges with Sepsis

Many challenges are present when initiating sepsis workups IV access

Limited sites for access

Inexperienced staff

Poor perfusion

Obtaining cultures Blood

Urine

CSF

Unstable patients

Obtaining consent

Importance of Intervention

Prior to the CDC putting out guidelines recommending the use of intrapartum antibiotic prophylaxis (IAP) to prevent perinatal GBS infections Incidence of EOS in the United States was 3-4 cases/1000 live births

After the guidelines were put out the rate of GBS-specific EOS declined to 0.3-0.4 cases/1000 live births Overall, EOS incidence declined to 0.8-1.0 cases/1000 live births

Risk Assessment in Neonatal Early Onset Sepsis Mukhopadhyay, Sagori ; Puopolo, Karen M. Seminars in Perinatology, December 2012, Vol.36(6), pp.408-415

Timing is Important “Cultures don’t Heal the Baby, Antibiotics do”

When sepsis is suspected, treatment must be immediate due to both the immunosuppression and non-specific signs

Antibiotics should be started as soon as diagnostics tests are performed

Timing of antibiotics is not researched a lot in Neonatology Most of the studies are in pediatrics and adults

Do not take into account the less effective immune system of the neonate

There is a lot of emphasis on not just when to initiate antibiotics, but also the timing between initiation of the sepsis work up and the timing of antibiotic administration

R. Moores, MD

Qualitiy Improvement at VCU

Committee to Improve Care

In 2012, a sepsis committee composed of RNs, MD, NNPs and Pham D started looking at our timing of antibiotic administration

Aspects of quality improvement were identified

Goals: Improve timing of antibiotic administration

Patients to receive antibiotics within 2 hours of diagnosis of sepsis

Pilot Study Showed a Major Concern

In 2012, a pilot study done by Sheila Pedigo (Pharm D) revealed that antibiotics were given anywhere between 3-5 hours from the time an order was placed

To note this is pharmacy data and not data collected in the NICU

Antibiotic Average time from order to administration

Range

Ampicillin (N=26) 3.9 hr 0.5-8.5 hr Gentamicin (N=28)

(EOS) 4.6 hr 1.5-15 hr

Gentamicin (N=22) (LOS)

3.8 hr 0.5-12 hr

Vancomycin (N=28) 3.4 hr 0.5-7 hr

Approach Used

Identify steps and time involved for individual components regarding work-up and treatment of neonatal sepsis

Evaluate data for barriers, if any, which delay expedient therapy for sepsis by medical staff, nursing, and pharmacy staff

Identifying Steps in Process for EOS Treatment Initiation Was the unit aware of the pending delivery? Yes_____No_____Time Aware?_____ Baby was born: __________ time L&D team left delivery room: __________time Baby arrived in the NICU: __________time Time antibiotics ordered? __________ Time antibiotics arrived on unit? _________ Did you receive them immediately after they arrived? Yes_____No____ time Blood culture initiated? __________time Blood culture completed? ________time Was an LP performed? If yes, Time initiated ________ Time completed_________ Line placement was initiated: __________Line placement was completed: __________time IV fluids started: __________time X-ray ordered: __________time X-ray completed: __________time X-ray read: __________time First antibiotic started: __________ finished __________time Name of antibiotic: __________ Second antibiotic started: __________ finished __________time Name of antibiotic: __________ Were there delays in the admission process? Yes___No____What were the delays? Time Giraffe Top Down if applicable__________

Identifying Steps in Process for LOS Treatment Initiation Please note the time of these actions when late onset sepsis is suspected What time did physician or NNP first articulate presumed sepsis? __________time What time was nursing notified? ___________time What time was order for antibiotics placed? __________time At the time of notification, did the infant have a suitable line for administration of

antibiotics? Y/N __________ If not, what time was line initiated? _______ What time was line completed? _________ Barriers to line placement? _______________________ Time antibiotics arrived on unit? ________Time at bedside? __________ Did you receive them immediately after they arrived? Yes___No________ Time Blood culture initiated? __________ Time Blood culture completed? ___________ Time LP initiated? ___________ Time LP completed? ______________ Urine culture initiated? _______ Urine culture initiated? _________time First antibiotic started: __________ finished __________time Name of Antibiotic ordered: __________ Second antibiotic started: __________ finished __________time Name of Antibiotic ordered: __________ Were there delays in the septic work-up process or administration of

antibiotics?Yes___No___ What were the delays?

Pharmacy Aspects Regarding Neonatal Sepsis Effective antimicrobial order verification for dose, dose interval, schedule

and product

Identify all aspects in the process involved in drug order verification to dispensing

Identify barriers, if any, which impact the process involved in drug order verification to dispensing

Findings

System wide problem

Needed to implement changes on multiple levels

NICU QI Committee Initial Recommendations Diagnostic Aspect

If RN not at bedside when decision made to implement sepsis workup, notify them immediately

Notify charge nurse and MD/NNP if no IV access obtained within 30 minutes No more than 3 attempts per provider

Communicate which antibiotic to be given first

Cultures Drawn prior to antibiotic administration if possible

MD/NNP should be notified if cultures are not obtained within 30 minutes of initiation

Recommendations

Antibiotic administration time target 2 hr for antibiotic administration (ideal goal 1 hour) 1 hr for dispensing from pharmacy (ideal goal 30 minutes)

Cultures Culture drawn before antibiotics – ideal

Drug flush volume 1 ml of normal saline

IM antibiotics NOT indicated

Revision of current sepsis protocol

Outcomes

There was a significant improvement in time between order entry to first dose of antibiotics Early Onset Sepsis: average 2.4 hours (decreased from 4.2 hours)

Late Onset Sepsis: average 2.2 hours (decreased from 5.3 hours)

Further Intervention

In 2013 Children’s Hospital of Richmond at VCU started a Pediatric Sepsis Committee

Includes all Pediatrics units (Wards, ED, PICU, NICU)

Goals Reduce mortality from sepsis by 10% (Hospitalwide)

Time to antibiotics: 70% of stat IV antibiotics have order to delivery time <60 minutes

Changes Implemented in the NICU During that Time Antibiotics were now stored in the PYXIS system on the unit for faster access

Only accessed if delay in delivery from pharmacy

Antibiotic doses were barcoded and scanned into the system at time of administration Improved accuracy of charting times of administration

New Sepsis protocol was now in use

Report of 2016

Improvements Needed

Became clear that even though we improved administration time in the QI initiative of 2012, more needed to be done

NICU sepsis committee met again and evaluated current processes

Findings presented to faculty and leadership in the NICU and new recommendations were suggested

Recommendations

Recommendations “unofficially” implemented as they are not finalized yet include: When sepsis is suspected the charge nurse, patient’s nurse, attending, fellow and

NP/resident huddle by the patient’s bedside to discuss findings and plan

Once decision to initiate sepsis work-up is made Attending/fellow/NP stay in the room with the patient until sepsis work-up is completed

Makes them readily available for questions, concerns, to help

Charge nurse stays and assists the nurse taking care of the patient with obtaining access, blood and urine culture, and getting needed supplies

A new form is filled out to document timing of events

Form Filled out by Nursing

Updated Results Through End of January

Updated Results Through End of January

Updated Results Through End of January

Updated Results Through End of February

Updated Results Through End of February

Updated Results Through April

Updated Results Through April

Future plans

Recommendations pending implementation as need more discussion and approval If lumbar puncture (LP) consent is not obtained

Bypass consent and obtain LP (needs two MDs to sign consent as life threatening)

Give antibiotics and obtain LP after

If any culture is not obtainable give antibiotics within the hour regardless (attending approval needed)

Update current sepsis protocol to include timeline of steps

Lessons Learned

There is always room to improve

Quality Improvement is never ending

Teamwork is very important to achieve goals and improve care

Education is very important to achieve goals and improve care

Thank you