Using very short-term heart rate variability to monitor fentanyl-induced changes in the autonomic nervous system preceding respiratory depression

Author: Anne-Louise Smith

Smith, Anne-Louise, 2011 Using very short-term heart rate variability to monitor fentanyl-induced changes in the autonomic nervous system preceding respiratory depression, Flinders University, School of Computer Science, Engineering and Mathematics

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Post-operative opioid analgesia to control pain is complicated by the occurrence of respiratory depression in 0.1-1% of patients with subsequent hypoxia. Timely detection of critical respiratory depression events such as loss of airway tone would be useful in preventing harm to these patients. The heart and airway have inherent vagal rhythms synchronous with the respiratory cycle; cardiac vagal tone and respiratory sinus arrhythmia can be monitored with heart rate variability (HRV). This study investigated whether a premonitory change in the HRV occurred with opioid-induced changes in airway stability. The opioid fentanyl was selected for its safe pre-operative use and short action time (5-6 min). This required establishment of HRV analysis over very short-term periods. The hypothesis was that a measure of short-term, non-stationary HRV could detect a change in vagal or sympathetic activity that may be a reflection of a shift in the stability of airway tone. The first part of this study identified 70 HRV indices suitable for short-term use from: time and spectral domain, Poincare plot and heart rate characteristics. The minimum window length of 30 beats was determined by analysis of Lomb-Scargle spectral indices. The indices were validated over 10x30 beat windows using PhysioNet databases with physiological states: at rest, active, exercising, sleeping, and meditating (N from 12 to 20). Baseline 95% confidence intervals of the median were established with bootstrap resampling (10,000). Statistical significance was assessed using the overlap of 95% confidence intervals. Correlation of subject average was used to remove redundant indices and a minimal set of 31 indices differentiated at least one of the physiological states from resting. The second part of this study applied the indices in a pilot observational study (N = 10) of the fentanyl effects on upper airway stability of healthy subjects scheduled for minor surgery. Physiological data (ECG, SpO2, ETCO2, flow and chest impedance) and clinical observations were recorded. Baseline data (7x30 beat) was compared to 10 consecutive 30-beat periods: a) post-fentanyl and b) peri-critical respiratory depression. Statistical significance was assessed with overlap of 95% confidence intervals for the median. All subjects had an initial central depression followed by a critical respiratory depression event (no flow). Five subjects developed clinically observed upper airway obstruction: two snoring and three with full sustained UAWO. The expected decreases in heart rate, total variability or sympathetic activity were not seen, nor was there a change in vagal activity in the post-fentanyl or peri-respiratory depression periods. Some subjects had consistently reactive HRV for many indices, but the changes were not related to the extent of respiratory depression. One index, PolVar20, detected a flurry of sympathetic activity, after fentanyl administration and before the critical respiratory depression in some subjects with sustained trends (statistically insignificant due to the skewed distribution). PolVar20 may indicate an attempt to restore airway patency after opioid-induced respiratory depression in a small subset of patients in the clinical setting; those not suffering from any cardiac autonomic neuropathy.

Keywords: opioid,survey,validation,Lomb-Scargle,Poincare

Subject: Medical Biotechnology thesis, Engineering thesis

Thesis type: Doctor of Philosophy
Completed: 2011
School: School of Computer Science, Engineering and Mathematics
Supervisor: Karen Reynolds