Respiratory Failure
Conditions
Keywords
Sedation, Cycling, Pediatric
Brief summary
The purpose of this study is to determine if the reduction of the total amount of sedative critically pediatric ill patients receive in the PICU will achieve a significant decrease in mechanical ventilation days and a decrease in the overall length of stay in the PICU and hospital.
Detailed description
Continuous sedative infusions have been associated with longer duration of mechanical ventilation, longer stay in the intensive care unit (PICU) and total hospital stay. Also, extended duration of continuous sedative infusions limits the ability to assess for adequate neurologic function. There is, however, no published data on the use of daily interruption of continuous sedative infusions in pediatric patients, nor are there any recommendations from the leading pediatric critical care groups regarding this issue. Infants and children exposed to noxious stimuli (endotracheal tube, endotracheal suctioning, mechanical ventilation, indwelling catheters) in addition to an unknown environment are less likely to cooperate during normal daily interventions in the PICU. Continuous infusions of benzodiazepines and opioids in addition to as needed (PRN) bolus doses have been the standard of care in our institution for mechanically ventilated patients. The study seeks to determine if reducing the total dose of sedatives, by holding them in a cyclical manner, will be a safe and effective intervention that will not increase adverse patient outcomes. This will be achieved by limiting the patient tolerance to the sedatives, decreasing the body total deposit of sedatives and subsequently decreases awakening time when patient is ready for extubation.
Interventions
DRUGMidazolam
DRUGNormal saline
DRUGFentanyl
Sponsors
Javier Gelvez, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
* Less than or equal to 18 years of age * Intubated and mechanically ventilated * Expected to require continuous infusions of sedatives for at least 48 hours * Parent or legal guardian available for informed consent * Males and females of any race are eligible
Exclusion criteria
* Less than 72 hours after surgery * Cyanotic heart disease with unrepaired or palliated right to left intracardiac shunt * Critical airway (according to PICU Attending) * Ventilator dependent (including noninvasive) on PICU admission * Greater than 48 hours of continuous sedation infusion(s) * Neuromuscular respiratory failure * Managed by patient controlled analgesia (PCA) or epidural catheter * Known allergy to any of the study medications (fentanyl or midazolam) * Family/Medical team have decided not to provide full support (patient treatment considered futile) * Patient requires ECMO * Head trauma requiring intracranial pressure monitoring * Pregnancy * Following resuscitation from cardiorespiratory arrest whose initial pH is \< 6.9 * ICU Attending judgment that patient should be excluded for safety reasons
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Mechanical Ventilation Days | From date of randomization until the date of discharge from PICU, assessed up to 1 month | Participants will be followed for an expected average of 4 days. The Data Safety Monitoring Group will review the data every 6 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PICU Length of Stay | From date of randomization until the date of discharge from PICU, assessed up to 1 month | Participants will be followed for an expected average of 7 days. This secondary endpoint is to be evaluated every six months. |
| Hospital Length of Stay | From date of hospital admission to date of hospital discharge, assessed up to 6 weeks | Participants will be followed for an expected average of 7 days in PICU and 10 days of hospitalization. This secondary endpoint is to be evaluated every six months. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental Group In this arm Fentanyl and Midazolam was replaced with placebo (normal saline) during cycling.
At cycling time for midazolam, the continuous infusion of midazolam was stopped by the bedside nurse. The nurse started a pump containing a syringe labeled Study Drug M which contained the placebo drug (normal saline). The switch to Study Drug M occurred twice daily at 0800 and 2000 for a period of 3 hours each. At cycling time for fentanyl, the continuous infusion of fentanyl was stopped by the bedside nurse. The pump containing a syringe labeled Study Drug F, which contained the placebo drug (normal saline), was started. The switch Study Drug F occurred twice daily at 1400 and 0200 for a period of 3 hours each.
Dosing was done per standard of care and not prescribed per protocol. | 14 |
| Control Group In this arm, midazolam and fentanyl were administered during cycling.
At cycling time for midazolam, the continuous infusion of midazolam was stopped by the bedside nurse. The nurse started a pump containing a syringe labeled Study Drug M which contained the control drug (midazolam). The switch to Study Drug M occurred twice daily at 0800 and 2000 for a period of 3 hours each. At cycling time for fentanyl, the continuous infusion of fentanyl was stopped by the bedside nurse. The pump containing a syringe labeled Study Drug F, which contained the control drug (fentanyl), was started. The switch to Study Drug F occurred twice daily at 1400 and 0200 for a period of 3 hours each.
Dosing was done per standard of care and not prescribed per protocol. | 11 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 3 | 3 |
| Overall Study | Protocol Violation | 3 | 0 |
Baseline characteristics
| Characteristic | Experimental Group | Control Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 14 Participants | 11 Participants | 25 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 0.24 years | .20 years | 0.22 years |
| Race/Ethnicity, Customized Race/Ethnicity African American | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Caucasian | 6 Participants | 5 Participants | 11 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic or Latino | 6 Participants | 6 Participants | 12 Participants |
| Region of Enrollment United States | 14 participants | 11 participants | 25 participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 1 / 11 |
| other Total, other adverse events | 7 / 14 | 2 / 11 |
| serious Total, serious adverse events | 2 / 14 | 1 / 11 |
Outcome results
Primary
Duration of Mechanical Ventilation Days
Participants will be followed for an expected average of 4 days. The Data Safety Monitoring Group will review the data every 6 months.
Time frame: From date of randomization until the date of discharge from PICU, assessed up to 1 month
Population: In October of 2012, the DSMB unanimously voted to close this study due to safety concerns and inactivity. The Board noted that recruitment goals had not been met and statistical analysis could not be made with current data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental Group | Duration of Mechanical Ventilation Days | 10.14 days | Standard Deviation 5.55 |
| Control Group | Duration of Mechanical Ventilation Days | 5.82 days | Standard Deviation 1.85 |
Secondary
Hospital Length of Stay
Participants will be followed for an expected average of 7 days in PICU and 10 days of hospitalization. This secondary endpoint is to be evaluated every six months.
Time frame: From date of hospital admission to date of hospital discharge, assessed up to 6 weeks
Population: In October of 2012, the DSMB unanimously voted to close this study due to safety concerns and inactivity. The Board noted that recruitment goals had not been met and statistical analysis could not be made with current data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental Group | Hospital Length of Stay | 25.21 days | Standard Deviation 16.69 |
| Control Group | Hospital Length of Stay | 20.82 days | Standard Deviation 17.8 |
Secondary
PICU Length of Stay
Participants will be followed for an expected average of 7 days. This secondary endpoint is to be evaluated every six months.
Time frame: From date of randomization until the date of discharge from PICU, assessed up to 1 month
Population: In October of 2012, the DSMB unanimously voted to close this study due to safety concerns and inactivity. The Board noted that recruitment goals had not been met and statistical analysis could not be made with current data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental Group | PICU Length of Stay | 13.93 days | Standard Deviation 7.49 |
| Control Group | PICU Length of Stay | 9.82 days | Standard Deviation 6.75 |