Clinical trial NCT03978819: ANI Parasympathetic Monitoring in Neurosurgery
Official title: Ability of the Analgesia Nociception Index Monitor to Distinguish Between Excessive Analgesia and Inadvertent Parasympathetic Nerve Stimulation During Surgery of Large Cerebellopontine Angle Tumours
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Bradycardia
Keywords: Analgesia nociception index
Parasympathetic nerve stimulation
Excessive analgesia
Lead sponsor: Association de Developpement de la Neuroanesthesie Reanimation
Sponsor class: OTHER
Collaborators: name: University of Bordeaux
First posted: 2019-06-07
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male or female with large cerebellopontine angle tumors (\>2 x 2 cm)

Brief summary: Surgery of large cerebellopontine angle (CPA) tumors (\>2 x 2 cm diameter), with compression of the pons exposes the patient to inadvertent parasympathetic nerve stimulation (IPNS) leading to bradycardia and asystole.

The analgesia nociception index (ANI) monitor assesses the balance between analgesia and nociception through the detection of parasympathetic tone. ANI \>80 generally denotes excessive analgesia (EA). The main objective of this study was to determine whether ANI values for IPNS are different or the same as ANI values for EA. This study also aims at calculating the number of patients with IPNS and EA during surgery of large CPA tumours.

Detailed description: Bradycardia and asystole are potential life threatning complications during surgery of large cerebellopontine angle (CPA) tumors (\>2 x 2 cm diameter), with compression of the pons.The incidence of such complications are unknown. One of the plausible mechanisms is inadvertent parasympathetic nerve stimulation (IPNS) due to the proximity of this cranial nerve to the CPA tumor. Monitoring parasympathetic nerve activity may provide further insight to the implication of this cranial nerve in the cardiac complications observed during surgery of large CPA tumors. The analgesia nociception index (ANI) monitor assesses the balance between analgesia and nociception through the detection of parasympathetic tone. Despite the abundant clinical reports about this index, to the knowledge of the investigators, only a few studies have been published in the neurological setting. Moreover, there are no data reporting the parasympathetic profile (measured by the ANI monitor) in situations of IPNS and EA. Are these profiles the same or different? Such is the main question this study thrives to answer. Understanding the behavior of parasympathetic nerve activity in this context could help provide the appropriate management strategy.

In order to answer this question, participants undergoing elective large CPA tumor surgery were included in this prospective observational study. Standard cardiorespiratory monitoring including heart rate (HR) was done. Target-controlled anesthesia with Propofol and Remifentanil was guided by a bispectral index of 30-40 and an ANI of 50-70 respectively. Data was continuously recorded with event markers at the onset of bradycardia (HR \< 45 bpm), asystole and the coincidence of ANI \> 80 with Remifentanil site effect \> 6 ng.ml-1 (defined as excessive analgesia).

Eligibility criteria: Inclusion Criteria:

* patients undergoing elective surgery of large cerebellopontine angle tumors

Exclusion Criteria:

* age below 18yr
* arrhythmia
* preoperative use of vagolytics, β-blockers and clonidine.

Primary outcomes:
measure: Differences in instantaneous ANI (ANIi) values during bradycardia versus ANIi values when Remifentanil effect size concentration >6ng/mL
timeFrame: ANIi values recorded at Day 1 only during surgery (duration: 4-6 hours)
measure: Differences in the area under the ROC curves between ANI values for IPNS and EA analgesia
timeFrame: ANIi values recorded at Day 1 only during surgery (duration: 4-6 hours)
Secondary outcomes:
measure: Percentages of IPNS and EA cases
timeFrame: Cases observed at Day 1 only during surgery (duration: 4-6 hours)
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU Bordeaux University Hospital
Study officials:
affiliation: ADNR, Neuroanesthesia and Critical Care, 33076 Bordeaux, France
name: Musa Sesay, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Neuroanesthesia and Critical Care, CHU University Bordeaux
name: Matthieu Biais, M.D., PhD
role: STUDY_DIRECTOR
affiliation: Neuroanesthesia and Critical Care, CHU University Bordeaux
name: Karine Nouette-Gaulain, M.D., Ph.D
role: STUDY_CHAIR
References:
citation: Renowden S. Imaging of the cerebello-pontine angle. Pract Neurol. 2014 Oct;14(5):e2. doi: 10.1136/practneurol-2014-000949. Epub 2014 Aug 12. No abstract available.
citation: Sesay M, Vignes JR, Stockle M, Mehsen M, Boulard G, Maurette P. [Spectral analysis of the ECG R-R interval permits early detection of vagal responses to neurosurgical stimuli]. Ann Fr Anesth Reanim. 2003 May;22(5):421-4. doi: 10.1016/s0750-7658(03)00094-7. French.
citation: De Jonckheere J, Rommel D, Nandrino JL, Jeanne M, Logier R. Heart rate variability analysis as an index of emotion regulation processes: interest of the Analgesia Nociception Index (ANI). Annu Int Conf IEEE Eng Med Biol Soc. 2012;2012:3432-5. doi: 10.1109/EMBC.2012.6346703.
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citation: Robin F, Sesay M, Kolanek B, Pena D, Penna M, Morel-Locket L et al. The analgesia nociception index monitor (ANI) can detect indvertent vagal stimulation during surgery of cerebello-pontine angle tumors. Br J Anaesth 2013;111: https: // doi.org/10.1093/bja/el_10195
citation: Kommula LK, Bansal S, Umamaheswara Rao GS. Analgesia Nociception Index Monitoring During Supratentorial Craniotomy. J Neurosurg Anesthesiol. 2019 Jan;31(1):57-61. doi: 10.1097/ANA.0000000000000464.
citation: Theerth KA, Sriganesh K, Reddy KM, Chakrabarti D, Umamaheswara Rao GS. Analgesia Nociception Index-guided intraoperative fentanyl consumption and postoperative analgesia in patients receiving scalp block versus incision-site infiltration for craniotomy. Minerva Anestesiol. 2018 Dec;84(12):1361-1368. doi: 10.23736/S0375-9393.18.12837-9. Epub 2018 Jul 9.
citation: Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis. Br J Anaesth. 2014 Jun;112(6):991-1004. doi: 10.1093/bja/aeu137.
citation: Galley HF. Editorial II: Solid as a ROC. Br J Anaesth. 2004 Nov;93(5):623-6. doi: 10.1093/bja/aeh247. No abstract available.