Can short-term heart rate variability be used to monitor fentanyl-midazolam induced changes in ANS preceding respiratory depression?

Opioids have an occasional but high-risk side effect of respiratory depression. The detection of critical respiratory depression usually occurs after the event. Earlier detection would be beneficial in preventing increased morbidity and mortality of 0.01 % patients receiving analgesic opioids. Airway patency during inspiration requires vagal modulation. Regulation of the cardiovascular and respiratory centres may be coupled with a central mechanism that is indirectly measurable with heart rate variability (HRV). While opioids tend to increase parasympathetic tone, a decrease in airway stability could be due to a decrease in respiratory parasympathetic activity. Sympathetic arousal generated by apneic events may separately be recognised with short-term HRV. This pilot observational study examined the dynamic sympathovagal changes during fentanyl-midazolam induced respiratory depression on 10 subjects scheduled for minor surgery. A selection of HRV indices, able to work over sub-minute periods on non-stationary signals, were applied including a range of less common indices. Three analyses tested the effects: post-fentanyl, preceding the first central depression, and preceding obstruction of the upper airway. Statistical significance was assessed with overlap of bootstrap percentile confidence intervals for the median. A decrease in total variability, Lomb Total using the Lomb-Scargle method, is a positive finding for short-term HRV use in this study. No significant change before critical respiratory events was observed in traditional, spectral power, respiratory or other indices. One index, PolVar20, indicated a burst of sympathetic activity preceding respiratory depression similar to sleep apnoea arousals that restore airway patency. Before its usefulness in early detection of airway tone can be determined, PolVar20 requires further work: a statistical method for highly skewed distributions, auto adjustment for baseline variability, and detecting a range of sympathetic responses to apnea.

Heart rate variability indices for very short-term (30 beat) analysis. Part 1: survey and toolbox.

Heart rate variability (HRV) analysis over very short (<60 s) periods may be useful for monitoring dynamic changes in autonomic nervous system activity where steady-state conditions are not maintained (e.g. during drug administration, or the start or end of exercise). From the 1980s there has been a wealth of HRV indices produced in the quest for better measures of the change in parasympathetic and sympathetic activity. Many of the indices have been sparingly used and have not been investigated for application to short-term use. This study surveyed published methods of HRV analysis searching for indices that could be applied to very short time HRV analysis. The survey included measures of time domain, frequency domain, respiratory sinus arrhythmia, Poincaré plot, and heart rate characteristics. Indices were tested with short segments of archived data to remove those that produced invalid results, or were mathematically equivalent to, but less well known than other indices. The survey identified a comprehensive list of 115 indices that were subsequently coded and screened. Of these, 70 were unique and produced a finite number with 60 s data, so are included in the Toolbox. These indices require validation against physiological data before they can be applied to short-term HRV analysis of cardiac autonomic nervous system activity.

Heart rate variability indices for very short-term (30 beat) analysis. Part 2: validation.

Heart rate variability (HRV) analysis over shorter periods may be useful for monitoring dynamic changes in autonomic nervous system activity where steady-state conditions are not maintained (e.g. during drug administration, or the start or end of exercise). This study undertakes a validation of 70 HRV indices that have previously been identified as possible for short-term use. The indices were validated over 10 × 30 beat windows using PhysioNet databases with physiological states of rest, active, exercising, sleeping, and meditating (N from 12 to 20). Baseline 95 % confidence intervals of the median were established with bootstrap resampling (10,000x). Statistical significance was assessed using the overlap of 95 % confidence intervals. Thirty-one indices could differentiate between resting and at least one physiological state using 30 beat windows. All respiratory sinus arrhythmia indices and Poincaré plot indices were strongly correlated to time domain measures (SDNN or RMSSD). Spectral indices using the Lomb-Scargle algorithm were able to correctly identify paradoxical shifts in power with meditation and reduced power in exercise. Some less-known indices gave interesting results: PolVar20 identified the higher sympathetic activity of exercise with the largest positive magnitude. These indices should now be considered for rigorous gold standard tests with pharmacological blockade.

Use of a systematic review to inform the infection risk for biomedical engineers and technicians servicing biomedical devices.

Many microorganisms responsible for hospital-acquired infections are able to stay viable on surfaces with no visible sign of contamination, in dry conditions and on non-porous surfaces. The infection risk to biomedical staff when servicing biomedical devices is not documented. An indirect approach has been used to examine the different aspects that will affect the risk of infection including a systematic review of microbial contamination and transmission relating to biomedical devices. A systematic review found 58% of biomedical devices have microbial contamination with 13% having at least one pathogenic organism. These microbes can persist for some months. Occupational-infections of biomedical service staff are low compared to other healthcare workers. A biomedical device with contaminated surface or dust was identified as the source of patient outbreaks in 13 papers. The cleaning agent most tested for removal of micro-organisms from devices was alcohol swabs, but sterile water swabs were also effective. However, manufacturers mainly recommend (74%) cleaning devices with water and detergent. Biomedical engineers and technicians have a small risk of being exposed to dangerous micro-organisms on most biomedical devices, but without skin breakage, this exposure is unlikely to cause ill-health. It is recommended that biomedical staff follow good infection control practices, wipe devices with detergent, sterile water or alcohol swabs as recommended by the manufacturer before working on them, and keep alcohol hand rubs accessible at all benches.

Warming blood prior to transfusion using latent heat.

OBJECTIVE: Major trauma is associated with blood loss and hypothermia. It is common to replace lost fluid with red cells stored at 2-6°C, and/or colloid/crystalloid fluid stored at ambient temperature, thus increasing hypothermia risk. At trauma and medical retrieval sites, mains electricity powered fluid warmers cannot be generally used. Latent heat provides an alternate practical method of portable temperature-controlled intravenous fluid warming. This work investigates the safety and efficacy of a fluid warmer powered by latent heat. METHODS: Twenty-five haematology patients received red cell transfusions, one through a fluid warmer, using latent heat from a super-cooled liquid and one without warming. Temperature of donor red cell units was measured after passing through fluid warmers. Blood samples were collected from red cell units and patients, prior and after each transfusion. These were tested for haemolysis markers (plasma haemoglobin, potassium, lactate dehydrogenase, bilirubin) and for traces of super-cooled liquid. Patient physiological parameters (oxygen saturation, pulse, temperature, blood pressure, respiration) were monitored during each transfusion. RESULTS: Patient's physiological signs remained stable and no transfusion reactions were observed during warm transfusions. Latent heat fluid warmers increased the temperature of red cell units to approximately 35°C. There were no significant differences in haemolysis markers following warmed and unwarmed transfusions, and no contamination of red cell units by super-cooled liquid was detected. CONCLUSION: The latent heat fluid warmer was shown to safely warm transfused blood in a controlled clinical setting.

Correlated Poincaré indices for measuring heart rate variability.

Poincaré indices are usually applied to HRV to summarise long data sets collected over 24 hrs. Many applications of HRV are interested in dynamic, short term changes (<1 min). This study uses Poincaré indices published through the 1990's to the present, to determine which of them are correlated over the short term (25 beats). Dynamic changes were observed in 12 subjects pre-operatively receiving fentanyl and midazolam sedation with ECG collected for 5 mins before and 5 mins after fentanyl administration. Poincaré indices with a strong correlation (r>0.85) between the indices for each of the 12 subjects (p<0.001) (particularly with the common measures SDNN, RMSSD, pNN50 and meanRR) were identified. These indices will not be used for further investigation of dynamic effects of fentanyl and midazolam, two sedative drugs used in anaesthesia and intensive care. Indices that proved less suitable for short term analysis (eg. presence of outliers, inability to produce a valid index with smaller number of beats) were also identified. A shortlist of Poincaré indices that do not correlate strongly with commonly used measures may prove interesting in determining dynamic characteristics of the effect of sedative drugs on autonomic nervous system activity.

Survey of Poincaré indices for measuring heart rate variability.

Multiple indices have been developed to characterise the nonperiodic behaviour of heart rate variability displayed in Poincaré plots, particularly with R-R interval data collected over 24hr periods. Some of these indices have been compared to statistical time-domain indices and some to spectral indices, while others have been used to separate data sets such as cardiac abnormalities. A survey of published indices for Poincaré plot analysis was made covering literature through the 1990's to the present day. Statistical time-domain indices and the surveyed Poincaré indices were used to analyse the same data set of R-R intervals that included: supine, standing, deep breathing, light exercise and recovery. This study examined these Poincaré indices and determined their correlations with time-domain indices, and investigated how the correlations are affected by analysing shorter time periods. Further investigation of the Poincaré indices that do not correlate strongly with SD or rMSSD may prove interesting in determining dynamic characteristics of cardiac nervous system activity.