The Effects of Ketamine on Respiratory Stimulation and Transpulmonary Pressures

NCT ID: NCT01969227

Last Updated: 2023-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2022-12-31

Brief Summary

Impairment of airway patency is a common cause of extubation failure and opioids and hypnotics can adversely affect airway patency. Ketamine, a noncompetitive antagonist of N-methyl-D-aspartate (NMDA), unlike other anesthetics activates respiratory effort and promotes bronchodilation. At subanesthetic plasma concentration, ketamine reduces both opioid and propofol requirements.

The purpose of this pharmaco-physiological interaction trial is to evaluate the effects of ketamine on breathing and electroencephalography in mechanically ventilated patients.

Detailed Description

Maintaining the patency of the upper airway in sedated and anesthetized patients is challenging especially when patients are ready to be weaned from mechanical ventilation. Spontaneous breathing trial (SBT) is used to expedite the weaning process, which oftentimes requires the reduction and/or discontinuation of sedatives and analgesics. In some surgical patients, reducing these medications can lead to pain associated agitation and inability to conduct SBTs, which may prolong the need for mechanical ventilation. Using medications with narcotic sparing effects and that do not cause respiratory depression may allow for the reduction or discontinuation of agents that depress respiratory drive and subsequently facilitate extubation.

Ketamine has been used for many years in critically ill patients for sedation and analgesia. This noncompetitive antagonist of N-methyl-D-aspartate (NMDA) is used as an anesthetic and analgesic and has been shown to reduce opioid consumption and to prevent the development of opioid tolerance. Unlike other anesthetics, ketamine activates respiratory effort and promotes bronchodilation. At subanesthetic plasma concentration, ketamine reduces both opioid and propofol requirements.

The goal of this pharmaco-physiological interaction trial is to evaluate the effects of ketamine at a subanesthetic dose on breathing and electroencephalography. The investigators hypothesize that ketamine drip at a subanesthetic infusion rate (low dose ketamine 5 - 10 mcg/kg/min) is associated with respiratory stimulating effects and does not markedly increase transpulmonary pressure in mechanically ventilated patients.

The primary outcome is respiratory function, assessed through peak inspiratory flow, tidal volume,respiratory rate, duty cycle, and minute ventilation measured 15 minutes prior to initiation of ketamine infusion (to serve as baseline), at 60 minutes of ketamine infusion at 5mcg/kg/min, at another 60 minutes of infusion at 10mcg/kg/min, at which point the infusion is stopped for 3 hours for a final set of measurements.

Conditions

Mechanical Ventilation; Airway Patency; Respiratory Depression

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort

Adult mechanically ventilated patients who are deemed eligible for a spontaneous breathing trial and are candidates to receive subanesthetic ketamine by the primary critical care team.

Group Type: EXPERIMENTAL

Subanesthetic ketamine

Intervention Type: DRUG

Ketamine drip at a subanesthetic infusion rate (low dose ketamine 5 - 10 mcg/kg/min)

Interventions

Subanesthetic ketamine

Ketamine drip at a subanesthetic infusion rate (low dose ketamine 5 - 10 mcg/kg/min)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years admitted to ICU requiring mechanical ventilation
• Suitable for spontaneous breathing trial
• Candidate to received low dose ketamine by the primary critical care team

Exclusion Criteria

• Esophageal injury
• Allergic to ketamine
• Known neurodegenerative disorders
• Major neurologic disorders (elevated ICP)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Lorenzo Berra, MD

Medical Director, Respiratory Care

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lorenzo Berra, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Matthias Eikermann, MD, PhD

Role: STUDY_DIRECTOR

Beth Israel Deaconess Medical Center

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Countries

United States

References

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Reference Type: BACKGROUND

PMID: 22108392 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 7823995 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 10624993 (View on PubMed)

Hirota K, Hashimoto Y, Sakai T, Sato T, Ishihara H, Matsuki A. In vivo spasmolytic effect of ketamine and adrenaline on histamine-induced airway constriction. Direct visualization method with a superfine fibreoptic bronchoscope. Acta Anaesthesiol Scand. 1998 Feb;42(2):184-8. doi: 10.1111/j.1399-6576.1998.tb05106.x.

Reference Type: BACKGROUND

PMID: 9509200 (View on PubMed)

Morel DR, Forster A, Gemperle M. Noninvasive evaluation of breathing pattern and thoraco-abdominal motion following the infusion of ketamine or droperidol in humans. Anesthesiology. 1986 Oct;65(4):392-8. doi: 10.1097/00000542-198610000-00008.

Reference Type: BACKGROUND

PMID: 3767037 (View on PubMed)

Kissin I, Bright CA, Bradley EL Jr. The effect of ketamine on opioid-induced acute tolerance: can it explain reduction of opioid consumption with ketamine-opioid analgesic combinations? Anesth Analg. 2000 Dec;91(6):1483-8. doi: 10.1097/00000539-200012000-00035.

Reference Type: BACKGROUND

PMID: 11094005 (View on PubMed)

Other Identifiers

2013P001690

Identifier Type: -

Identifier Source: org_study_id