Clinical trial NCT04049656: Confirmatory Study of HFVI Guided Analgesic Administration in Surgical Subjects
Official title: A Prospective, Randomized, PACU Blinded, Clinical Utility Study to Confirm the Safety and Efficacy of HFVI-Guided Analgesic Administration in Surgical Subjects Receiving Balanced Sevoflurane-Fentanyl Anesthesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Analgesia
Keywords: Sevoflurane-Fentanyl Anesthesia
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: Mdoloris Medical Systems
First posted: 2019-08-08
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A Prospective, Randomized, PACU Blinded, Clinical Utility Study to Confirm the Safety and Efficacy of HFVI-Guided Analgesic Administration in Surgical Subjects Receiving Balanced Sevoflurane-Fentanyl Anesthesia
Primary purpose: SUPPORTIVE_CARE

Brief summary: The current study is intended to be a prospective clinical performance validation study designed to confirm the clinical utility of HFVI-guided fentanyl administration during sevoflurane anesthesia.

The overall objective of this study is to confirm the safety and efficacy of HFVI-guided analgesic administration in comparison to standard clinical practice. The primary efficacy endpoint will be the amount of postoperative pain reported in the PACU, as measured using a nurse administered Numerical Rating Scale (NRS) pain score.

Detailed description: HFVi was designed to provide a standardized measure of the parasympathetic component (p∑) of the Autonomous Nervous System (ANS). It tracts changes of the p∑ tonus induced by each respiratory cycle (spontaneous or artificial) to measure the relative balance of parasympathetic and sympathetic tone as reflected in the EKG signal.

These rapid changes of the p∑ tonus express themselves at the sinus node level by changes of the time interval separating two R waves of the electrocardiogram. The following normal RR intervals constitute the tachogram (displayed as respiratory pattern on the monitor). The p ∑ component is evaluated after filtering, standardization and re-sampling of the R-R series, by measuring the surface generated by respiratory cycles on the tachogram. Higher p∑ tonus is reflected as a larger measured surface area. In contrast, the measured surface decreases when the p∑ decreases.

HFVi, a measure of the surface area, is expressed in the form of a dimensionless index ranging from 0 to 100. This index reflects the relative activity of the parasympathetic nervous system. It expresses the relative quantity of the present p∑ tonus compared to the Para and sympathetic tonus. The measure of HFVi displayed represents the average of a sequence of measurements: each elementary measure is realized on 64 seconds of data, updated each second using a sliding window.

During development, a probabilistic interpretation of the HFVi was used to relate index values to a clinical state in an anesthetized subject. A significant hemodynamic response (increase of the heart rare or blood pressure of 20% compared to the baseline) within 10 minutes was used as an indicator of nociception/inadequate analgesia.

As a measure of parasympathetic tone, HFVi may be influenced by many factors and thus be difficult to interpret in many of the following situations:

* arrhythmia
* no breathing (ex : apnea due to intubation)
* Respiratory rate lower than 9 cycles/min
* Tidal volume variable on the measuring time, thus 64 seconds
* Irregular breathing (when the patient speaks, laugh or cough)
* pace maker (some types)
* heart transplantation
* Drug use having a significant effect on the sinus cardiac activity

Eligibility criteria: Inclusion Criteria:

* Able to provide informed consent
* American Society of Anesthesiologist Physical Status 1 or 2
* Body Mass Index range of 19-35 kg.m-2.
* Planned spinal or open abdominal surgery expected to last 1-3 hours utilizing a balanced sevoflurane-fentanyl general anesthetic

Exclusion Criteria:

* Subjects are unable or unwilling to give informed consent.
* Emergency surgery
* Women who are currently pregnant or not using a medically acceptable means of birth control
* Cardiac morbidity, including non-regular sinus cardiac rhythm or implanted cardiac pacemaker
* Concurrent medications with a major effect upon the sinus node including prescribed antimuscarinic agents, α2-adrenergic agonists, β1-adrenergic antagonists, and antiarrhythmic agents
* Expected duration of surgery less than 1 hour (60 minutes) or greater than 3 hours (180 minutes)
* Pre-operative chronic opioid use or chronic pain, equivalent to requiring oxycodone 20mg per oral, per day for more than 6 weeks
* Allergy or intolerance to any of the anticipated study medications, such as history of malignant hyperthermia during anesthesia
* Planned use of neuraxial anesthesia
* Clinically significant abnormality or clinically significant unstable medical condition, as indicated by medical history, physical examination, ECG results, or clinical laboratory testing, that in the Investigator's judgment might pose a potential safety risk to the subject or limit interpretation of the trial results, e.g., any uncontrolled thyroid disorders, hepatic, cardiac, pulmonary and renal malfunctioning.

Primary outcomes:
measure: Change in Numerical Pain Scores (NPS)
timeFrame: 15 minutes; 30 minutes; 45 minutes; 60 minutes
Secondary outcomes:
measure: Percentage of patients minimal pain (NPS < 3) during recovery
timeFrame: Hour 1
measure: Number of opioid analgesics administered in the operating room (OR) and post-anesthesia care unit (PACU).
timeFrame: Hour 1
measure: Incidence of postoperative nausea and vomiting (PONV) in the PACU
timeFrame: Hour 1
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: UF Health Jacksonville
state: Florida
Study officials:
affiliation: University of Florida
name: Jay W Johansen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: