Cycling of Sedative Infusions in Critically Ill Pediatric Patients

Not Applicable

Terminated

Conditions: Respiratory Failure

Interventions: Drug: Midazolam
Drug: Normal saline
Drug: Fentanyl

Registration Number: NCT01333059

Lead Sponsor: Javier Gelvez, MD

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 25

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental Group	Midazolam	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
Experimental Group	Normal saline	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
Control Group	Midazolam	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.
Experimental Group	Fentanyl	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
Control Group	Fentanyl	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.