Sevoflurane- Safety in Long-term Sedation Procedures

Renal Function Clinical Trial

Official title:

Study of the Safety of Administration of Sevoflurane for Long-term Critically Ill Patients Sedation Undergoing Mechanical Ventilation. Prospective, Controlled, Randomized, Multicenter, Clinical Trial.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01802255
• Other study ID #: ECSEVO-LT-011
• Secondary ID: 2011-002555-34
• Status: Withdrawn
• Phase: Phase 3
• Start date: March 2013
• Est. completion date: June 2015

Study information

• Verified date: August 2021
• Source: Fundación para la Investigación del Hospital Clínico de Valencia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients needing intensive care often require sedative drugs to reduce anxiety and agitation during ventilator care and invasive therapeutic and diagnostic procedures. At present there is no optimal sedative agent for these patients. The most commonly used sedative agents in intensive care units are midazolam and propofol. Both drugs have side effects of clinical importance.

At present, a viable alternative to intravenous sedation is inhalatory sedation. Sevoflurane, as other inhaled anesthetic agents, is sedative in low doses. A new simplified method of administration of isoflurane or sevoflurane has been developed. The Anesthetic Conserving Device is a modified heat-moisture exchanger (HME) that permits direct infusion of sevoflurane to the airway, where it is vaporized in an evaporator rod in the device.

However, the use of sevoflurane is limited to anesthesia and sedation lasting no more than 12 hours, since the possible renal problems posed by inorganic fluoride in prolonged operations remain the subject of controversy.

The primary aim (and primary hypothesis) of the current trial is to determine whether sevoflurane can be administered as a sedative drug for more than 48 hours without clinically relevant physiopathological effects on kidney and liver function.

Other end-points of the trial are to evaluate the quality of sedation of sevoflurane, in terms of sedation control, the rapidity and predictability of awakening, and the incidence of delirium in critical care patients.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signing of the informed consent document (patient or relatives).

• Patient age 18 years or older.

• Expected minimum duration of sedation: 48 hours.

Exclusion Criteria:

• Chronic renal failure treated with replacement therapy (hemodialysis or peritoneal dialysis).

• Acute kidney injury in Stage 3 of AKIN classification

• Grade C hepatic Child-Pugh classification

• Established Acute Respiratory Distress Syndrome (ARDS).

• Central nervous system pathology with cognitive disorders that not allow performing the test of the study: severe dementia, Alzheimer's disease, depression, schizophrenia, acute stroke.

• Head trauma with Glasgow <12.

• Patient treated with antiepileptic drugs that must be maintained during the study period

• Patients requiring the use of neuromuscular blocking agents during the infusion of study drug, except for the insertion of the endotracheal tube.

• Epidural or spinal analgesia

• Allergy or known hypersensitivity to any of the study drugs

• Patients with known or suspected genetic susceptibility to malignant hyperthermia

• Previous participation in this trial

• Participation in another clinical trial within 4 weeks prior to selection.

• Pregnant women

Related Conditions & MeSH terms

• Fluoride Poisoning
• Hepatic Function
• Poisoning
• Poisoning by Inhaled Anaesthetic
• Recovery From Sedation
• Renal Function

Intervention

Drug:
• Sevoflurane
Sedation with inhaled anesthetic via AnaConDa.
• Midazolam
Intravenous sedation.

Locations

Country	Name	City	State
Spain	Hospital Clínico Universitario de Valencia	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
F Javier Belda

Country where clinical trial is conducted

Spain, 

References & Publications (2)

Kong KL, Bion JF. Sedating patients undergoing mechanical ventilation in the intensive care unit--winds of change? Br J Anaesth. 2003 Mar;90(3):267-9. — View Citation

Röhm KD, Wolf MW, Schöllhorn T, Schellhaass A, Boldt J, Piper SN. Short-term sevoflurane sedation using the Anaesthetic Conserving Device after cardiothoracic surgery. Intensive Care Med. 2008 Sep;34(9):1683-9. doi: 10.1007/s00134-008-1157-x. Epub 2008 May 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maintenance of renal function.	Measurements in plasma: creatinine and cystatin levels.	Baseline. Posteriorly, every 12 hours for the full length of sedation. After sedation, every 24 hours up to one week
Secondary	Assessment of liver function	Measurements in plasma: SGOT (aspartate aminotransferase, AST), SGPT (alanine aminotransferase, ALT), LDH (lactate dehydrogenase) alkaline phosphatase, conjugated and total bilirubin, cholesterol, triglycerides, albumin, total proteins, electrolytes and glycogen.	Baseline. Posteriorly, every 12 hours for the full length of sedation. After sedation, every 24 hours up to one week
Secondary	Plasma pharmacokinetics of fluoride	Determine evolutionary plasmatic levels of fluorides.	Baseline. Posteriorly, every 12 hours for the full length of sedation. After sedation, every 24 hours up to one week
Secondary	Incidence of delirium	The incidence of delirium will be evaluated by the CAM-ICU method.	Baseline. Posteriorly, every 12 hours for the full length of sedation. After sedation, every 24 hours up to one week