Study of High Blood Sugars and Insulin in Hospitalized, Critically Ill Children
Condition: Critical Illness; Hyperglycemia
MeSH terms: Hyperglycemia; Critical Illness
Study type: Interventional

Summary: 
      BACKGROUND AND PURPOSE

      Critical illness hyperglycemia (CIH) - elevated blood glucose in the critically ill patient
      population - has gained much interest among health care providers over the past several
      years. Clinical studies in adults have documented a high rate of hyperglycemia in some
      post-surgical and medical intensive care units (ICUs). However, the primary reasons for
      interest in this topic are not due just to its high rate, but also to the fact that by
      returning the high glucose levels found in this population to normal with insulin therapy can
      dramatically improve clinical outcomes by decreasing both morbidity and long-term mortality.
      Because of this, aggressive glucose control has become common practice in adult ICU critical
      care management.

      Although there is substantial data describing the high incidence of CIH in adult patients,
      there is little information regarding this condition in children. A single retrospective
      study recently published also suggested a high incidence of CIH in children with critical
      illness secondary to both medical and surgical causes. It is yet to be determined if, like in
      adults, normalizing blood glucose levels with insulin improves outcomes in this pediatric
      population. Because evidence appears compelling that hyperglycemia is both common and
      detrimental in adults, many pediatric ICUs have likewise begun to focus on aggressively
      treating hyperglycemia in critically ill children.

      The proposed study is a prospective observational pilot study to occur in the Pediatric
      Intensive Care Unit (PICU) at Children's Healthcare of Atlanta at Egleston. This prospective
      pilot study is being done to evaluate the endocrine factors associated with, if not
      responsible for, CIH, and the changes that take place with the restoration of normal blood
      glucose levels by insulin therapy.

      To address these profound issues this study will pursue two interrelated Aims:

      Aim #1: To determine if critical illness hyperglycemia is associated with absolute insulin
      deficiency, peripheral insulin resistance, or both.

      Aim #2: To characterize the requirement of insulin required to initially restore and maintain
      normal blood glucose levels, and compare the changes in insulin that take place with this
      normalization in patients with CIH.

      We hypothesize that the hyperglycemic response to critical illness will be associated with
      abnormally low levels of insulin as compared to patients without critical illness
      hyperglycemia.
    

Detailed description: 
      SUMMARY OF PROCEDURES

      This will be an approximately 12 month long, single center, prospective study of patients
      between ages 2 and 12 years old who meet criteria for CIH in our pediatric intensive care
      unit during the period of enrollment. Patients will be screened by physicians and staff and
      evaluated via inclusion and exclusion criteria, the evaluation will discussed with the
      family/legal guardian by appointed critical care fellow, attending or physician appointee,
      and the patient will be enrolled if informed consent is granted. Following informed consent
      approval from family/legal guardian, blood samples will be collected and sent for storage and
      processing in the clinical laboratory at Children's.

      Three patient population groups will be assessed in this study:

        -  Group A - Study Patients - At risk for CIH/with CIH Labs will be drawn in our target
           population at diagnosis of CIH and sent for insulin and C-peptide levels. These levels
           will be repeated 24 hours after initiation of insulin, and then followed every three
           days until insulin is no longer needed, then repeated once more 24 hours after insulin
           is off (see protocol).

        -  Group B - Control Patients - At risk for CIH/without CIH Insulin and C-peptide levels
           will be drawn in a control group of patients with the same risk factors but without CIH
           at the time of admission, 24 hours after admission, then in 3 days.

        -  Group C - Control Patients - Not at risk for CIH/without CIH The same protocol of lab
           schedules will be used in a second control group consisting of patients that are not
           deemed at risk for critical illness hyperglycemia.

      III. POTENTIAL RISKS

      Most patients who meet criteria usually have an arterial line, central venous catheter, or
      "blood drawing" IV. It will be rare that a separate venous puncture will be needed to collect
      samples. If the blood to be collected, approximately 2cc per stick, is believed to negatively
      impact the patient by either the patient or clinical caretakers, blood will not be drawn.

      Information collected in this study will contain Protected Health Information (PHI) on
      subjects. There is the potential risk of unintentional disclosure of this information.
      However, certain steps will be followed in this study minimalize PHI disclosure to help
      protect the subjects' privacy and confidentiality. Once collected, this information will be
      kept in a database that is password protected and with limited access on a password-protected
      network. Other than institutions required by law to have access to research records, only
      authorized research staff will have access to the research database associated with the
      study. Furthermore, no data will be identifiable to study subjects, as each subject will be
      assigned a unique study number when entered into a database. If published or presented, no
      identifying features will be provided.

      IV. POTENTIAL BENEFITS

      There may be no direct potential benefit to the subjects participate in this study. However,
      the information learned from this study may benefit other patients in the future.

      V. INCLUSION AND EXCLUSION CRITERIA

      Inclusion:

      - All patients between ages 2 and 12 years of age admitted to the pediatric ICU who meet
      criteria for critical illness hyperglycemia (ie: all patients on mechanical ventilation, all
      patients on vasoactive medications, patients deemed otherwise "at risk" for CIH by attending
      service) and are started on our standard CIH screening and treatment protocol will comprise
      the pool of potential study candidates.

      Exclusion:

      - Certain patients who meet criteria for critical illness hyperglycemia and thus are started
      on insulin will be excluded from this study: Age Patients less than 2 or greater than 12
      years of age will be excluded from this study to decrease age variability.

      Pre-existing known endocrine disorder Patients with known or suspected Type 1 diabetes will
      be excluded because of their pre-existing absolute lack of insulin production secondary to
      autoimmune β cell destruction.

      Oncology patients Oncology patients will be excluded because of the effects of
      immunosuppressants on study markers.

      Renal replacement therapy Patients on continuous veno-venous hemofiltration (CVVH) or any
      type of dialysis (intermittent dialysis, peritoneal dialysis) will be excluded as it is
      unclear how different forms of renal replacement therapy affect insulin levels, and certain
      types of dialysis affect glucose and insulin levels (i.e. dextrose containing PD fluid).

      Non-adherence Inability or unwillingness of the legal guardian to provide consent, or
      unwillingness of the child to provide assent.

      VI. INFORMED CONSENT PROCESS

      Patients will be considered eligible for this study at the discretion of the pediatric
      intensivists or their appointees (i.e. pediatric critical care fellows or nurse
      practitioners). There will be discussion with the family of the background information,
      reasons for conducting the study, and the risks involved. At any time during the study there
      will be opportunity to be removed from the study without impact on care. After all questions
      have been answered, written informed consent will be obtained from the parents (or legal
      guardian), and signed by the intensivist or appointee.

      If the parent/subject decides not to participate, the child will continue with their standard
      of care procedures as originally planned without any further testing.

      As part of the ongoing informed consent process, whenever appropriate, the subjects
      participating in this study will be provided with additional pertinent information after
      initial time of consent.
    

Intervention name(s): Serum Lab testing
Intervention type(s): Other
Intervention description(s): Serum Lab testing
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment