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Bulletin of Experimental Biology and Medicine, Vol. 155, No. 6, October, 2013 METHODS
Mass-Spectrometric Monitoring of Anesthesia Adequacy A. Yu. Elizarov, A. V. Kozlovsky, I. I. Tupitsyn, and I. I. Faizov
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 155, No. 6 pp. 780-783, June, 2013 Original article submitted April 24, 2012 Anesthesia adequacy was assessed with mass-spectrometric method by monitoring the ratio of mass concentrations of end-tidal CO2 and inhaled O2 in every respiratory cycle during surgery. For real-time monitoring, we used a mass spectrometer with electron ionization connected to the respiratory contour of inhalation anesthesia machine. The study has demonstrated advantages of the novel method in real-time assessment of adequacy of the total intravenous anesthesia. Key Words: intravenous anesthesia; propofol; fentanyl; metabolism; mass spectrometry Anesthesia protects the organism against CNS overload during surgery aggression. However, it should be carefully gaged not to disturb the work of vital organismal systems beyond the admissible physiological limits. At present, physicians renewed their interest in the use of total intravenous anesthesia (TIVA) [4], which does not employ an inhalation anesthetic agent. Instead, the medicinal drugs in this case are analgesic fentanyl, hypnotic propofol, and myorelaxant esmeron. TIVA components are less toxic than those of balanced inhalation anesthesia based on the use of inhalation anesthetic, analgesic, and hypnotic agents [3], which is characterized by non-invasive monitoring of concentration of the inhalation analgesic in the respiratory contour of inhalation anesthesia machine (IAM) measured with incorporated IR sensor. TIVA is carried out with due account for the blood concentrations of intravenous preparations calculated per unit body weight. The usual practice is continuous intravenous infusion of an anesthetic agent with an auto syringe pump, which can deliver the drug at a wide range of infusion rates. However, maintenance of optimal anesthesia under the conditions of persistently changing degree of surgery aggression is rather difficult, because there is no reliable ways to control the degree of pain and to monitor the real-time concentration of anesthesia A.F. Ioffe Physics and Technology Institute, Russian Academy of Sciences, Saint Petersburg, Russia. Address for correspondence:
[email protected]. A. Yu. Elizarov
agents in the blood. Recent papers reported the measurements of concentration of intravenous hypnotic drug propofol in the exhalation contour based on mass spectrometry [1,5-8]. Despite these achievements, the real-time assessment of anesthesia adequacy is still an urgent problem for practical anesthesiology.
MATERIALS AND METHODS The level of anesthesia is an important factor affecting the rate of metabolic processes. Inadequate anesthesia (such as overdosage) results in extra release of CO2, hypercapnia, and respiratory alkalosis leading to general intoxication of the organism. The primary evidence of this abnormality is delayed consciousness recovery. Hence, the concentrations of CO2 and O2 are the most important parameters to be continuously monitored during artificial ventilation [3]. The work of medical sensors detecting CO2 level is based on absorption of infrared light (4.2 μ). The response times of CO2 optical sensors employed to monitor the gas mixtures in IAM respiratory contour are 450 msec (Phasein), 640 msec (Philips Healthcare), 400 msec (GE Healthcare), 600 msec (Dräger Medical), and 500 msec (Datascope). To measure O2 concentration, the sensors employ the electrochemical reactions with a too large response time, which excludes the possibility to monitor O2 content in IAM respiratory contour during inhalation and exhalation phases. In contrast, to measure CO2 and O2 concentrations during these
0007-4888/13/15560814 © 2013 Springer Science+Business Media New York
A. Yu. Elizarov, A. V. Kozlovsky, et al.
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Fig. 1. CO2 monitoring during inspiration and expiration (m/z=44 AMU). a) Capnography during TIVA period and b) the dynamics of carbon dioxide mass concentration Mout(CO2) measured in every respiratory cycle. Here and in Fig. 2: the stages of surgery. I: insertion of nasal dilator; II: excision of chondral and osseous parts of the nasal septum; III: opening the anterior wall of sphenoid sinus cavity; IV: opening of the dura mater; V: tumorectomy; VI: hemostasis.
phases in the real-time mode, we used a time-of-flight mass spectrometer with resolving power 50 m/m. The resolving power in measurement of partial pressure of gases was 10-12 mbar. Temporal resolution in the trend analysis during simultaneous measurement of CO2 and O2 concentrations was 10 msec. The ratio of mass concentrations of exhaled CO2 and inhaled O2 (absorbed during the inspiration phase) was calculated by integrating the trend-analysis plot for every respiratory cycle: N=Mout(CO2)/Min(O2), where Mout(CO2) and Min(O2) are the mass concentrations of exhaled CO2 and inhaled O2 in single respiratory cycle, correspondingly. The boundaries of the respiratory cycle were determined as the minima of capnogram and oxygram, correspondingly, which were established with differentiation. For convenient data presentation, the relative changes of CO2 and O2 were normalized for N≡1 in the first respiratory cycle. The measurements have been carried out during the transnasal pituitary adenoma resection (n=10). The patients were not grouped for age and sex. Induction anesthesia was performed with intravenous propofol (2 mg/kg body weight) simultaneously injected with myorelaxant and fentanyl (0.4 μg/kg body weight). During the entire period of anesthesia, fentanyl (0.1 mg) was repeatedly injected i.v. every 20 min (Table 1). Maintenance of TIVA was achieved by target-controlled infusion of propofol according to its concentration in blood plasma maintained with the help of automated Diprifusor pump (B|Braun Medical Inc.). The changes in the target concentration during anesthesia have been made to provide stability of AP (Table 1). The two-stage system of vacuum differential pumping was employed to take the samples of gaseous mixture directly from Y-piece (Dräger) connected
to the endotracheal tube in IAM respiratory contour. Vacuum in mass-spectrometer was maintained with a turbo molecular pump (pumping speed 60 liter/sec). The gas mixture was pump out of respiratory contour with the rate of 0.5 ml/min [2]. The initial stage of anesthesia (2-3 min) could not be examined because connection of mass spectrometer to the respiratory contour was difficult in the period when the mode of artificial ventilation switched from laryngeal mask airway to endotracheal tube.
RESULTS Figure 1 shows the dynamics of concentration of exhaled carbon dioxide during inspiration-expiration phases of respiratory cycle and the results of calculation of Mout(CO2) used to obtain the dynamics of N. The dependence of N on anesthesia time is shown in
Fig. 2. Dynamics of N during anesthesia.
Bulletin of Experimental Biology and Medicine, Vol. 155, No. 6, October, 2013 METHODS
816 TABLE 1. TIVA Medicamentous Regimen
Anesthesia, min Drug 0-3
20
23
33
53
58
Propofol, μg/kg
3
—
2
0.5
2
—
Fentanyl, mg
—
0.1
—
—
0.1
—
Note. Dashes mean that the drug was not injected.
Fig. 3. Capnogram (a) and oxygram (b) during anesthesia.
Fig. 2. All the surgery stages changed the amplitude of the respiratory cycle and increased CO2 release in dependence on the degree of surgery aggression. After the end of short-term painful surgery manipulations (“painful stimulus”), the release of CO2 diminished for a short time, but on the whole, it persistently increased during the entire period of anesthesia (Fig. 1, a) reflecting up-regulation of metabolism in narcotized patient. In addition, the painful “stimulus” produced dramatic changes in oxygram (m/z=32 AMU) manifested by the surges in the trend-analysis plot (Fig. 3) resulting in pronounced “spikes” in N-plot. Thus, the changes in the value of N can be used as a criterion of anesthesia adequacy, which is corroborated by the dependence of metabolism on surgery stimulation. The analyzed example of surgery, i.e. transsphenoidal (transnasal) pituitary adenoma resection, attested to a certain insufficiency of anesthesia in this particular case (Fig. 2). In this study, we also compared the auditory evoked potentials with the changes in N-value provoked by bolus administration of propofol (100 mg). Both approaches detected the action period of the drug (30 min). Thus, monitoring CO2 and O2 in the exhaled air with mass spectrometry and assessing the level of pro-
pofol in blood plasma, one can provide the real-time control of TIVA adequacy. We are grateful to the personnel of Department of Anesthesiology and Reanimatology, and Neurosurgery Clinic of S. M. Kirov Military Medical Academy for the help in carrying out the experiments. This work was supported by the Russian Foundation for Basic Research (grant No. 12-08-00402).
REFERENCES 1. A. Yu. Elizarov and A. I. Levshankov, Zh. Tekh. Fiz., 81, No. 4, 155-158 (2011). 2. A. Yu. Elizarov, T. D. Ershov, A. V. Kozlovsky, and A. I. Levshankov, Mass-Spektrom., 8, No. 2, 143-146 (2011). 3. V. V. Likhvantsev, Anesthesia in Minimally Invasive Surgery [in Russian], Moscow (2005). 4. I. Smith and P. White, Total Intravenous Anesthesia [Russian translation], Moscow (2006). 5. A. Critchley, T. S. Elliott, G. Harrison, et al., Int. J. Mass Spectrom., 239, Nos. 2-3, 235-241 (2004). 6. G. R. Harrison, A. D. Critchley, C. A. Mayhew, and J. M. Thompson, Br. J. Anaesth., 91, No. 6, 797-799 (2003). 7. C . Hornuss, S. Praun, J. Villinger, et al., Anesthesiology, 106, No. 4, 665-674 (2007). 8. A. Takita, K. Masui, and T. Kazama, Anesthesiology, 106, No. 4, 659-664 (2007).
