The discriminatory value of cardiorespiratory interactions in distinguishing awake from anaesthetised states: a randomised observational study

Depth of anaesthesia monitors usually analyse cerebral function with or without other physiological signals; noninvasive monitoring of the measured cardiorespiratory signals alone would offer a simple, practical alternative. We aimed to investigate whether such signals, analysed with novel, non-linear dynamic methods, would distinguish between the awake and anaesthetised states. We recorded ECG, respiration, skin temperature, pulse and skin conductivity before and during general anaesthesia in 27 subjects in good cardiovascular health, randomly allocated to receive propofol or sevoflurane. Mean values, variability and dynamic interactions were determined. Respiratory rate (p = 0.0002), skin conductivity (p = 0.03) and skin temperature (p = 0.00006) changed with sevoflurane, and skin temperature (p = 0.0005) with propofol. Pulse transit time increased by 17% with sevoflurane (p = 0.02) and 11% with propofol (p = 0.007). Sevoflurane reduced the wavelet energy of heart (p = 0.0004) and respiratory (p = 0.02) rate variability at all frequencies, whereas propofol decreased only the heart rate variability below 0.021 Hz (p < 0.05). The phase coherence was reduced by both agents at frequencies below 0.145 Hz (p < 0.05), whereas the cardiorespiratory synchronisation time was increased (p < 0.05). A classification analysis based on an optimal set of discriminatory parameters distinguished with 95% success between the awake and anaesthetised states. We suggest that these results can contribute to the design of new monitors of anaesthetic depth based on cardiovascular signals alone

Regulation of human cutaneous circulation evaluated by laser Doppler flowmetry, iontophoresis, and spectral analysis: importance of nitric oxide and prostaglandines

Nitric oxide (NO) and prostaglandines (PGs) are important in regulation of vascular tone and blood flow. Their contribution in human cutaneous circulation is still uncertain. We inhibited NO synthesis by infusing N-G-monomethyl-L-arginine (L-NMMA) in the brachial artery (16 mumol/min for 5 min) and reversed it by intraarterial infusion Of L-arginine (40 mumol/min for 7.5 min). PG synthesis was inhibited by the cyclooxygenase inhibitor aspirin (600 mg over 5 min intravenously). Basal cutaneous perfusion and perfusion responses during iontophoresis with the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator sodium nitroprusside (SNP) were recorded by laser Doppler flowmetry (LDF). We performed wavelet transforms of the measured signals. Mean spectral amplitude within the frequency interval from 0.0095 to 1.6 Hz and mean and normalized amplitudes of five intervals around 1, 0.3, 0.1, 0.04, and 0.01 Hz were analysed. The oscillations with frequencies around 1, 0.3, 0.1, and 0.04 Hz are influenced by the heartbeat, the respiration, the intrinsic myogenic activity of vascular smooth muscle, and the neurogenic activity of the vessel wall, respectively. We have previously shown that the oscillation with a frequency around 0.01 Hz is modulated by the vascular endothelium. L-NMMA reduced mean value of the LDF signal by approximate to20% (P = 0.0067). This reduction was reversed by L-arginine. Mean value of the LDF signals during ACh and SNP iontophoresis did not change after infusion Of L-NMMA. Aspirin did not affect mean value of the LDF signal or the LDF signal during ACh or SNP iontophoresis. Before interventions the only significant difference between the effects of ACh and SNP was observed in the frequency around 0.01 Hz, where ACh increased normalized amplitude to a greater extent than SNP. L-NMMA abolished this difference, whereas it reappeared after infusion Of L-arginine (P = 0.0084). Aspirin did not affect this difference (P = 0.006). We conclude that basal cutaneous blood flow and the endothelial dependency of the oscillation around 0.01 Hz are partly mediated by NO, but not by endogenous PGs. Other aspects of human cutaneous circulation studied are not regulated by NO or PGs. (C) 2003 Elsevier Science (USA). All rights reserved

The Effects of General Anesthesia on Human Skin Microcirculation Evaluated by Wavelet Transform.

BACKGROUND: Time-frequency analysis of the laser Doppler flowmetry signal, using wavelet transform, shows periodic oscillations at five characteristic frequencies related to the heart (0.6–2 Hz), respiration (0.15– 0.6 Hz), myogenic activity in the vessel wall (0.052– 0.15 Hz), sympathetic activity (0.021– 0.052 Hz), and very slow oscillations (0.0095– 0.021), which can be modulated by the endothelium-dependent vasodilator acetylcholine. We hypothesized that wavelet transform of laser Doppler flowmetry signals could detect changes in the microcirculation induced by general anesthesia, such as alterations in vasomotion and sympathetic activity. METHODS: Eleven patients undergoing faciomaxillary surgery were included. Skin microcirculation was measured on the lower forearm with laser Doppler flowmetry and iontophoresis with acetylcholine and sodium nitroprusside before and during general anesthesia with propofol, fentanyl, and midazolam. The laser Doppler flowmetry signals were analyzed using wavelet transform. RESULTS: There were significant reductions in spectral amplitudes in the 0.0095–0.021 (P < 0.01), the 0.021–0.052 (P < 0.001), and the 0.052–0.15 Hz frequency interval (P < 0.01) and a significant increase in the 0.15–0.6 Hz frequency interval. General anesthesia had no effect on the difference between acetylcholine and sodium nitroprusside on relative amplitudes in the 0.0095–0.021 Hz frequency interval (P < 0.001). CONCLUSION: General anesthesia reduces the oscillatory components of the perfusion signal related to sympathetic, myogenic activity and the component modulated by the endothelium. However, the iontophoretic data did not reveal a specific effect on the endothelium. The increase in the 0.15–0.6 Hz interval is related to the effect of mechanical ventilation

Low-frequency oscillations of the laser Doppler perfusion signal in human skin

Spectral analysis of the laser Doppler flow (LDF) signal in the frequency interval from 0.0095-2.0 Hz reveals blood flow oscillations with frequencies around 1.0, 0.3, 0.1, 0.04 and 0.01 Hz. The heartbeat, the respiration, the intrinsic myogenic activity of vascular smooth muscle, the neurogenic activity of the vessel wall and the vascular endothelium influence these oscillations, respectively. The first aim of this study was to investigate if a slow oscillatory component could be detected in the frequency area below 0.0095 Hz of the human cutaneous blood perfusion signal. Unstimulated basal blood skin perfusion and enhanced perfusion during iontophoresis with the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator sodium nitroprusside (SNP) were measured in healthy male volunteers and the wavelet transform was computed. A low-frequency oscillation between 0.005 and 0.0095 Hz was found both during basal conditions and during iontophoresis with ACh and SNP. Iontophoresis with ACh increased the normalized amplitude to a greater extent than SNP (P  =  0.001) indicating modulation by the vascular endothelium. To gain further insight into the mechanisms for this endothelium dependency, we inhibited nitric oxide (NO) synthesis with NG-monomethyl-l-arginine (l-NMMA) and prostaglandin (PG) synthesis by aspirin. l-NMMA did not affect the increased response to ACh vs. SNP iontophoresis in the 0.005-0.0095-Hz interval (P  =  0.006) but abolished the difference in the 0.0095-0.021-Hz interval (P  =  0.97). Aspirin did not affect the difference in response to ACh and SNP in either of the two frequency intervals. Thus, other endothelial mechanisms, such as endothelium-derived hyperpolarizing factor (EDHF), might be involved in the regulation of this sixth frequency interval (0.005-0.0095 Hz)

Impaired cerebrovascular reactivity after acute traumatic brain injury can be detected by wavelet phase coherence analysis of the intracranial and arterial blood pressure signals

The objective of the study was to evaluate the wavelet spectral energy of oscillations in the intracranial pressure (ICP) signal in patients with acute traumatic brain injury (TBI). The wavelet phase coherence and phase shift in the 0.006-2 Hz interval between the ICP and the arterial blood pressure (ABP) signals were also investigated. Patients were separated into normal or impaired cerebrovascular reactivity, based on the pressure reactivity index (PRx). Spectral energy, phase coherence and phase shift in the low frequency and cardiorespiratory intervals were compared for the two groups. Data were prospectively collected and analyzed retrospectively in 22 patients, within the first week after acute TBI. The ICP and ABP signals were continuously recorded for 40 min and the wavelet transform was used to calculate the spectral energy and phase of the signals. The average ICP wavelet energy spectrum showed distinct peaks around 1.0 (cardiac), 0.25 (respiratory) and 0.03 Hz. Patients with normal cerebrovascular reactivity (negative PRx) had 38.6 % (+/- SD 16.7 %) of the mean wavelet energy below the lower limit of the respiratory frequency band (0.14 Hz) compared to only 18.1 % (+/- SD 17.8 %) in patients with altered cerebrovascular reactivity (positive PRx) (difference: p = 0.0057). Wavelet phase coherence between the ABP and ICP signals was statistically significant (p < 0.05) in the 0.006-2 Hz interval. The phase shift between the ABP and ICP signals was around zero in the 0.14-1.0 Hz interval. Seven patients with PRx between -0.4943 and -0.1653 had a phase shift in the interval 0.07-0.14 Hz, whereas 15 patients with PRx between -0.1019 and 0.3881 had a phase shift in the interval 0.006-0.07 Hz. We conclude that the wavelet transform of the ICP signal shows spectral peaks at the cardiac, respiratory and 0.03 Hz frequencies. Normal cerebrovascular reactivity seems to be manifested as increased spectral energy in the frequency interval < 0.14 Hz. A phase shift between the ICP and ABP signals in the interval 0.07-0.14 Hz indicates normal cerebrovascular reactivity, while a phase shift in the interval 0.006-0.07 Hz indicates altered cerebrovascular reactivity