Ketamine Infusion and Hypoventilation

• ClinicalTrials.gov Identifier: NCT01535976
• Recruitment Status: Completed
• First Posted: February 20, 2012
• Results First Posted: April 1, 2014
• Last Update Posted: April 1, 2014
• Sponsor: Northwestern University
• Information provided by (Responsible Party): Gildasio De Oliveira, Northwestern University

Study Description

Brief Summary:

Procedures performed under sedation have the same severity in regards to morbidity and mortality as procedures performed under general anesthesia1. The demand for anesthesia care outside the operating room has increased tremendously and it poses, according to a closed claim analysis, major risks to patients . Both closed claim analysis identified respiratory depression due to oversedation as the main risk to patients undergoing procedures under sedation. The major problem is that hypoventilation is only detected at very late stages in patients receiving supplemental oxygen. Besides the respiratory effects of hypoventilation, hypercapnia can also lead to hypertension, tachycardia, cardiac arrhythmias and seizures.

The incidence of anesthetized patients with obstructive sleep apnea has increased substantially over the last years along with the current national obesity epidemic. These patients are at increased risk of hypoventilation when exposed to anesthetic drugs. The context of the massive increase in procedural sedation and the extremely high prevalence of obstructive sleep apnea poses major respiratory risks to patients and it may, in a near future, increase malpractice claims to anesthesiologists. The development of safer anesthesia regimen for sedation are, therefore, needed. The establishment of safer anesthetics regimen for sedation is in direct relationship with the anesthesia patient safety foundation priorities. It addresses peri-anesthetic safety problems for healthy patient's. It can also be broadly applicable and easily implemented into daily clinical care.

Ketamine has an established effect on analgesia but the effects of ketamine on ventilation have not been clearly defined. The lack of validated and sensitive instruments to evaluate the effects of ketamine on ventilation is an important reason for the conflicting results.The investigators have demonstrated that the transcutaneous carbon dioxide monitor is accurate in detecting hypoventilation in patients undergoing deep sedation. Animal data suggest that when added to propofol in a sedation regimen, ketamine decreased hypoventilation when compared to propofol alone. It is unknown if ketamine added to a commonly used sedative agent (propofol) can decrease the incidence and severity of hypoventilation in patients undergoing deep sedation. It is also unknown if the effect of ketamine on ventilation are different in patients with and without obstructive sleep apnea.

The investigators hypothesized that patients receiving ketamine and propofol will develop less intraoperative hypoventilation than patients receiving propofol alone. The investigators also hypothesized that this effect will be even greater in patients with obstructive sleep apnea than patients without obstructive sleep apnea.

Significance: Respiratory depression due to oversedation was identified twice as the major factor responsible for claims related to anesthesia. The high prevalence of obstructive sleep apnea combined with more complex procedures done in outpatient settings can increase physical risks to patients and liability cases to anesthesiologists. The main goal of this project is to establish the effect of ketamine in preventing respiratory depression to patients undergoing procedures under sedation. If the investigators confirm the their hypothesis , their findings can be valuable not only to anesthesiologist but also to other specialties ( Emergency medicine, gastroenterologists, cardiologists, radiologists) that frequently performed procedural sedation. The research questions is;does ketamine prevent hypoventilation during deep sedation? The hypotheses is; ketamine will prevent hypoventilation during sedation cases.

Condition or disease	Intervention/treatment	Phase
Hypoventilation	Drug: Placebo; Drug: Ketamine	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: The Effect of Ketamine in The Prevention of Hypoventilation in Patients With and Without a Positive Berlin Questionnaire Undergoing Deep Sedation
• Study Start Date: August 2011
• Actual Primary Completion Date: May 2013
• Actual Study Completion Date: May 2013

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; .9 normal saline infusion	Drug: Placebo; Placebo Comparator: Placebo .9 normal saline infusion
Active Comparator: Ketamine; Infusion of ketamine	Drug: Ketamine; Ketamine infusion .5mg/kg bolus followed by 1.5 mcg/kg/minute until end of case

Outcome Measures

Primary Outcome Measures :

1. Intraoperative Hypoventilation [ Time Frame: 8 hours ]
   Subjects receiving intraoperative ketamine in addition to propofol will demonstrate less hypoventilation during the surgical procedure.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 64 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• ASA I,II
• Age 18-64
• Females undergoing surgical procedures requiring sedation

Exclusion Criteria:

• Pregnant subjects
• Breastfeeding

• Patients or surgeon request

  ---Drop Out:

• Patient or surgeon request,
• Conversion to general anesthesia
• Inability to obtain data from Co2 monitor

Contacts and Locations

Locations

United States, Illinois

Prentice Womens Hospital

Chicago, Illinois, United States, 60611

Sponsors and Collaborators

Northwestern University

Investigators

• Principal Investigator: Gildasio De Oliveira, MD; Northwestern University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

De Oliveira GS Jr, Fitzgerald PC, Hansen N, Ahmad S, McCarthy RJ. The effect of ketamine on hypoventilation during deep sedation with midazolam and propofol: a randomised, double-blind, placebo-controlled trial. Eur J Anaesthesiol. 2014 Dec;31(12):654-62. doi: 10.1097/EJA.0000000000000025.

• Responsible Party: Gildasio De Oliveira, Gildasio De Oliveira, M.D. Principal Investigator, Northwestern University
• ClinicalTrials.gov Identifier: NCT01535976
• Other Study ID Numbers: STU00048723
• First Posted: February 20, 2012
• Results First Posted: April 1, 2014
• Last Update Posted: April 1, 2014
• Last Verified: February 2014

Additional relevant MeSH terms:

Hypoventilation; Respiratory Insufficiency; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Ketamine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action