A Comprehensive Care Plan for Pediatric Patients With Vaso-Occlusive Crises

Sickle cell disease (SCD) disease is inherited as an autosomal recessive trait that results
in several interactive processes: polymerization of hemoglobin S (HbS), hemolysis, nitric
oxide depletion, and vaso-occlusion.[3] The most common manifestations of sickle cell disease
are vaso-occlusive pain events, specifically dactylitis which typically occurs as the first
clinical manifestation.[4] As patients age, the early onset peripheral pain moves to more
central regions resulting in increased severity of vaso-occlusive crises.[4] Pain from the
blockage of sickeled cells in vessels causes poor blood flow to a localized area. There are
few clinical and laboratory findings to indicate the severity of pain associated with sickle
cell crisis,[4] making it difficult for a physician to identify the amount of pain the
patient actually experiences. Length of stay in the hospital depends largely on physician
discretion and patient report.

Sleep is instrumental to many aspects of physical and emotional health during childhood and
adolescence. Sleep disruption from pain is a significant concern in patients with sickle cell
disease due to the prevalence of their acute and chronic pain.[7] In a study conducted by
Daniel et al., sickle cell patients between 4-10 years old, were more likely to exhibit
disrupted sleep, specifically night-waking and sleep-disordered breathing, than children who
were not diagnosed with sickle cell disease from similar demographic backgrounds. [7]
Furthermore, children with more severe forms of sickle cell disease were reported to have
more restless sleep than children with less severe forms. [7] Overall, the literature
suggests that sleep disruptions may interfere with children's daily functions, along with
their ability to cope with SCD and its complications.[7] Daniel et al. recommends discussing
ways to improve sleep habits with children suffering from SCD because it may increase
efficacy in pain management, priapism, and enuresis.[7] Another study by Valrie etal.,
suggests that poor quality of sleep is correlated with increased occurrence of sickle cell
disease pain the following day.[9] They also discovered that high pain severity was related
to poor sleep quality and this relationship was exacerbated during stressful situations.[9]
Developing a suitable sleeping environment (e.g. removing the television, or limiting the
lighting) will maximize sleep efficacy resulting in better health outcomes and quality of
life.[7] There has been minimal research on evaluating the relationship between exercise and
sickle cell disease in children and adolescents. Studies conducted on sickle cell disease in
adults with respect to the effects of exercise have produced mixed results partly due to
patient comorbid illnesses. In 2012, Chirico et al. compared two fitness level group
including, subjects who did not partake in regular physical activity for two years prior to
the study versus subjects who partook in regular, weekly physical activity for several years
leading up to the study. [5] Both groups contained sickle cell trait carriers and subjects
with normal hemoglobin. [5] Subjects performed an incremental maximum exercise test while
data was collected on heart rate via a chest monitor and on oxidative stress levels via blood
samples at various points following completion of the exercise task. [5] Results indicated
regular physical activity helped to blunt the increase in oxidative stress and the decrease
in nitric oxide metabolism and up regulation of antioxidant enzyme activities in response to
exercise in sickle cell trait carriers. [5] These findings suggest an attenuated sickle cell
crisis in the subjects with regular exercise when compared with the sedentary group.

Presently, at Phoenix Children's Hospital, no protocol exists for management of sleep and
exercise in sickle cell patients. The most relevant policy named "Parenting and Visitation"
includes guidelines regarding sleep and visiting hours but these are not well enforced. In
our hospital, the sickle cell population is known to have some of the longest length of
stays. Between October 2014 and September 2015, there were 89 admissions for a vaso-occlusive
crisis with an average length of stay of 6 days and 12 admissions greater than 10 days and 5
admissions greater than 20 days. Prior research suggests that implementation of standardized
care (e.g. order sets, protocols, and flowcharts) can improve compliance and patient outcomes
[8], reduce overall length of stay, and mitigate costs. Therefore, we have developed a new
comprehensive care plan (CPP) that enhances standard of care by including the following care
aspects:

1. Patient Controlled Analgesia (PCA). PCA will be initiated and managed at the discretion
of the Pain Management team. Naloxone infusion will be available for opioid related side
effects. Once tapered, patients will be transitioned to oral opioids to be administered
as needed. Patients will be discharged home, when appropriate, with oral opioids and
weaning instructions.

2. Other Medications. All medications will be given during daytime hours, if possible. All
home medications will be continued while inpatient. Ketorolac will be given
intravenously every 6 hours for 12 doses then switched to ibuprofen by mouth every 6
hours until discharge home. Stool softeners will be utilized while on narcotics to
prevent constipation. A clonidine patch may be used for adjunct analgesia and
anxiolysis. A lidocaine patch may be used for localized pain.

3. Pain Psychology. Consultations will begin on Day 2 and continue as needed. The
psychologist will teach the patient sleep hygiene techniques, and non-pharmacologic pain
management skills including: distraction, diaphragmatic breathing, progressive muscle
relaxation, and guided imagery with medical hypnosis.

4. Physical Therapy. Consultations will begin on Day 2 and continue as needed. Patient is
expected to spend time out of bed by Day 2 participating in light activity.

5. Sleep Hygiene. Will be introduced to the experimental group. Patient must sleep between
the hours of 10 PM and 5 AM daily. Window blinds will be open by 8 AM. Patient must be
awake and ready to participate in therapies by 9 AM. Napping will be at the discretion
of the physician. Practitioners should examine care orders critically, such as routine
vital signs, and determine if it is safe and/or appropriate to defer these during sleep.
Room lights will be turned off to help promote the circadian rhythm. No video games,
television, cell phones, or computers will be allowed during this time.

6. Extracurricular. Will participate in child life activities as recommended (e.g.
Playroom, or Zone). TV, phone, computer, and video games only between hours of 4-9 PM
(computer okay outside of hours only for school work).

7. Other. Patient will eat meals during regular daytime hours (e.g. breakfast consumed
before 9 am) and shower daily. No overnight visitors will be allowed.

We propose to evaluate the feasibility of the new CPP in a pilot randomized control trial to
determine if pain and length of stay can be reduced in patients with sickle cell disease. We
also propose to evaluate a sleep regimen to determine if this can reduce the hospital stay
and help with pain. We hypothesize increased physical activity and proper sleep, as
implemented in the CPP, are correlated with decreased hospital length of stay and decreased
pain. Additionally, we believe that creating a standardized nighttime environment at the
hospital will help the children stay in their circadian rhythm thus promoting improved sleep
and a more effective inpatient disease management.

Specific Aims Primary: To determine the feasibility and efficacy of the CPP to reduce pain
and length of stay in patients with sickle cell disease.

A.To evaluate if patients who follow the CPP physical activity regimen will have less pain
and shorter hospital stay than patients receiving standard of care.

B.To measure if patients who follow the CPP sleep activity regimen will have less pain and
shorter hospital stay than patients receiving standard of care.

Study Design This is a prospective pilot study of 20 subjects who have sickle-cell disease
and are admitted to Phoenix Children's Hospital for an acute vaso-occlusive crisis. Patients
will be randomized via a random number generator with equal probability of assignment to
either CPP (experimental) or standard of care (control) trial arm. Eligible subjects and
their family will be approached during the first day of hospital admission for consent to
participate and randomization. After randomization, all subjects will be given multiple
questionnaires to evaluate their current sleep habits, activity levels, and psychological
constructs Procedures During the enrollment visit, questionnaires will be administered to
every subject to evaluate current sleep habits, activity levels, pain, and quality of life.
Subjects will receive the Actiwatch Spectrum Pro and be given instructions on how to use it.

Control Group: Patient will receive standard of care. Nursing staff will be aware of study
presence but will not receive any specific instruction for the patient.

Experimental Group: During the enrollment visit, patient will go over the new comprehensive
care protocol with the study staff and will sign the agreement stating compliance. Patient
will be given a copy of the comprehensive care plan for reference. Nursing staff will be
aware of study's presence and will help to support patient's compliance with sleep and other
procedures according to care plan.

Discharge Study staff will closely follow the patient's progress in the hospital. Once
patient is ready for discharge, they will have a visit with study investigators and be given
one final PedsQL™ to complete. An additional questionnaire will be given to the experimental
group asking their opinion about the CPP. The Actiwatch Spectrum Pro will be collected from
the patients and be properly disinfected.

Measurement/Assessments Actiwatch Spectrum Pro Monitoring Device The Actiwatch Spectrum Pro
activity device will continuously monitor activity (active minutes), sleep (minutes slept and
quality) and allow the subject to input their numerical pain or fatigue rating. At the end of
the patient's trial, the data will be extracted from the actiwatch and placed into the
patient's alphanumeric account that is monitored by the research personnel. Patients or
families will not have access to the accounts. We will examine the minutes of activity per
day and minutes of sleep per day and compare it to the pain scores recorded by looking at the
data extracted from the Actiwatch Spectrum Pro.

Analysis Baseline characteristics will be summarized within the two care groups using
descriptive statistics including count and percent for categorical variables and the mean and
standard deviation (median and interquartile ranges) for continuous variables. Evaluation of
the CPP with length of stay will be done using the T-test or the Kruskal-Wallis test,
depending on the length of stay distribution. Analysis of variance for repeated measures will
assess the effect of time on pain scores within care groups. Differences in mean cumulative
pain scores between care groups will also be examined daily during hospital stay.

Additional analyses will investigate the association of care components, physical activity
and sleep, with length of stay and pain scores using appropriate statistical methods as
described above. All statistical tests will have a significance level of 0.05.

Inclusion Criteria:

- Children between 12 and 18 years of age who are admitted to the hospital for an acute
vaso-occlusive crisis

- Patients must require a demand PCA and able to tolerate oral pain medications

Exclusion Criteria:

- - Requires a continuous PCA

- Unwilling to be compliant with the assigned arm of study (e.g. Non-compliance with
sleep or visiting regimen, or questionnaires)

- Non-English speaking child or parent (questionnaires not available/validated in
another language)