PRINCIPAL INVESTIGATOR :         

David Greenhalgh, MD, FACS
Shriners Hospital for Children, Northern California
Department of Burn Surgery
2425 Stockton Boulevard
Sacramento , CA  95817
Phone: (916) 453-2051
Fax: (916) 453-2139
e-mail:  Dghalgh@shrinenet.org         

CO- INVESTIGATOR:                      

Tina Palmieri, MD, FACS
Shriners Hospital for Children, Northern California
Department of Burn Surgery
2425 Stockton Boulevard
Sacramento , CA  95817
Phone: (916) 453-2050
Fax: (916) 453-2139
e-mail:  TPalmieri@shrinenet.org

RESEARCH FELLOW:                     

Michael Shay O’Mara, MD
Shriners Hospital for Children, Northern California
Department of Burn Surgery
2425 Stockton Boulevard
Sacramento , CA  95817
Phone: (916) 453-2050
Fax: (916) 453-2139
e-mail:  momara@shrinenet.org

COORDINATORS:                           

Mary Beth Lawless, RN, MSN             
Johanna Sanders, RN, BSN
Shriners Hospital for Children, Northern California
Clinical Research, Burns
2425 Stockton Boulevard
Sacramento , CA  95817
Phone: (916) 453-2133
Fax: (916) 453-2139
e-mail:  Mlawless@shrinenet.org
Jjsanders@shrinenet.org

Description of Study

Dexamethasone to Prevent Reintubation in Children with Burns, A Multicenter Prospective Study

BACKGROUND

Swelling in the upper airway is a major concern in any person with a burn injury.  Since the airway is smaller in children, they are more prone to airway obstruction from the burn.  Many children are intubated simply to protect the airway from this swelling.  Once a child is intubated, it becomes a challenge to extubate the child without airway obstruction.  It is not uncommon for the child to develop stridor and ultimately the need to be reintubated.  Once stridor develops, there are only a few therapeutic options that reduce the need for re-intubation.  The use of a helium/nitrogen mixture (Heliox) or racemic epinephrine is only moderately successful.  Any therapy that would assist with preventing stridor would be of great use for the patient.

One of the most commonly used methods for minimizing swelling is by treating patients with preextubation steroids.  Dexamethasone is the most commonly used agent for minimizing airway edema.  Markovitz and Randolph recently published a meta-analysis of the 6 randomized controlled trials using steroids to prevent stridor or prevent the need for reintubation in pediatric patients.  Three of these trials were in neonates and three were in children.  Of the trials in children, one involved giving steroids after stridor developed.  Of the remaining two pediatric studies, the patients were given dexamethasone 0.5 mg/kg (maximum, 10 mg) with the first dose 6-12 hours before extubation, then every 6 hours for 6 total doses.  For the combined 5 prophylactic studies, there was a trend toward reduced rate of reintubation that did not reach statistical significance (n = 376, relative risk [RR] = 0.34, 95% confidence interval [CI] = 0.05 – 2.33).  The meta-analysis did reveal a statistically significant reduction in stridor with the use of steroids (RR = 0.5, 95% CI = 0.28 – 0.88).  In the neonatal studies, there was a trend for the reduction in reintubation (n = 160, RR = 0.2, CI = 0.04 – 1.11).  For the pediatric trials, there was no reduction in reintubation rates (n = 216, RR = 0.49, 95% CI = 0.01 – 19.65).  Postextubation stridor was reduced, however (RR = 0.53, 95% CI = 0.28 – 0.97).  In summary, to date no study has proven the efficacy of preextubation steroids to reduce the need to reintubate patients after extubation. 

Burn patients have a high rate of endotracheal intubation because of airway edema.  Once the patient is intubated, there is a significant risk with the development of stridor and a need for reintubation after extubation.  There are protocols in many burn units to give steroids after extubation with the hope of reducing stridor and reintubation.  No study, however, supports their use.   Since so many of our patients are intubated for edema, we have the potential for proving or disproving the efficacy of steroid prophylaxis for the prevention of the need for reintubation.  Since children are at the highest risk (due to their smaller airways) the study will focus on children 8 years old or less.  By including several burn centers, we should be able to answer the question of whether dexamethasone can reduce the need for reintubation after extubation in burned children.

OBJECTIVES

Dexamethasone has been used for years to reduce edema prior to extubation. Steroids have unwanted potential ill-effects. It should be determined whether steroids are necessary to prevent the need for reintubation. The specific aim of this proposal is to determine the efficacy of pre-extubation dexamethasone to reduced the need of reintubation in children with burns.

HYPOTHESIS

We hypothesize that pre-extubation dexamethasone reduces the need for reintubation in children with burns by reducing upper airway edema.

PATIENT SELECTION CRITERIA

Inclusion Criteria

• Any child 8 years old or younger admitted to SHCNC with thermal burns requiring intubation.
• Subjects/legal representatives, who have read, understood and signed a written informed consent.

Exclusion Criteria

• Persons older than 8 years.
• No burn injury.
• Airway trauma prior to intubation.
• Individuals with hepatic, renal failure, malignancy or neurologic injury
• No consent.

STUDY PROCEDURES

After consent, the subject will be randomized to one of the two groups.  One group will receive dexamethasone 0.5mg/kg (maximum 10mg) 6-12 hours before extubation and then every 6 hours for 5 more doses after the tube has been removed for a total of six doses. The other group will receive a saline placebo on the same schedule as the dexamethasone group. 

The patients will be monitored and medically managed per standard protocol for extubation. Additionally, the patient will be monitored for stridor and retractions with scores recorded immediately, at 30 and 60 minutes following extubation.

Adjuvant agents such as racemic epinephrine and Heliox may be used per standard treatment to avert reintubation.

POTENTIAL DISCOMFORTS AND RISKS

The risks of dexamethasone although rare, include hypertension (elevated blood pressure, hyperglycemia (elevated blood sugar) and thrombocytopenia (decreased platelets.) There is also a small risk of increased infection or impaired wound healing. 

Reintubation may be necessary should the patient not tolerate extubation. Additional treatments with agents such as racemic epinephrine and Heliox may be used per standard treatment to avert reintubation.

BENEFITS

No direct benefit to subjects is guaranteed, however, it is expected that subjects will experience an easier transition following extubation. 

STATISTICAL METHODS, DATA ANALYSIS AND INTERPRETATION

This is a prospective, randomized, double-blind, placebo-controlled, multicenter study to help determine if the drug dexamethasone significantly reduces the reintubation rate in pediatric burn patients.  Statistical analysis will include the relative risk (RR) and confidence interval for the primary endpoint; reintubation as well as for the secondary endpoints; stridor and the need for edema reducing agents. 

The data will be published as current practice in burn care.  It will then be used to develop standard treatment amongst burn hospitals.  Each study site will complete the Data Collection Form for each patient.  Each patient will be identified by a unique study number, with the first number corresponding to the site and the second number corresponding to the subject ID.  For example, patients at SHCNC could be identified by 01-001, 01-002, etc. The research coordinator at SHCNC will enter data into Excel and the principle investigator will transfer data to any required statistical programs.

PERIOD OF TIME ESTIMATED TO COMPLETE STUDY

Any child admitted with a burn injury to the participating Burn Units will be screened for the study. We expect to enroll 15 subjects at SHCNC over a two-year period as well as 300 patients from participating sites.  The plan for 300 patients is based on the meta-analysis by Markovitz and Randolph(1) that demonstrated no difference in the need for reintubation for 216 pediatric patients.

ADMINISTRATIVE RESPONSIBILITIES

Each participating site is responsible for obtaining IRB approval at their site.  A list linking subject ID to medical record number will be kept at each site, but will not be transferred to SHCNC.  The SHCNC research coordinator will collect Electronic and hard copies of the Data Collection Forms.  Data will be kept in a secure office and/or on a password protected computer.  The forms will not contain any protected health information. 

The principal investigator and staff will be responsible for data analysis, presentation of the study at a national meeting, and manuscript preparation.

References

• 1) Markovitz BP, Randolph AG. Corticosteroids for the prevention of reintubation and postextubation stridor in pediatric patients: A meta-analysis. Pediatr Crit Care Med 3:223-226, 2003.
• 2) Anene O, Meert KL, Uy H, et al. Dexamethasone for the prevention of postextubation airway obstruction: A prospective, randomized, double-blind, placebo-controlled trial. Crit Care Med 24: 1666-1669, 1996.
• 3) Tellez DW, Galvis AG, Storgion SA, et al: Dexamethasone in the prevention of postextubation stridor in children. J Pediatr 118: 289-294, 1991.
• 4) Courtney SE, Weber KR, Siervogel RM, et al. Effects of dexamethasone on pulmonary function following extubation. J Perinatol 12: 246-251, 1992.
• 5) Ferrara TB, Georgieff MK, Ebert J, et al. Routine use of dexamethasone for the prevention of postextubation respiratory distress. J Perionatol 9: 287-290, 1989.
• 6) Couser RJ, Ferrera B, Falde B, et al. Effectiveness of dexamethasone in preventing extubation failure in preterm infants at increased risk for airway edema.  J Pediatr 121: 591-596, 1992.