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Background: The pleth variability index (PVI) is a new algorithm used for automatic estimation of respiratory variations in pulse oximeter waveform amplitude, ...
Acta Anaesthesiol Scand 2010; 54: 596–602 Printed in Singapore. All rights reserved

r 2010 The Authors Journal compilation r 2010 The Acta Anaesthesiologica Scandinavica Foundation ACTA ANAESTHESIOLOGICA SCANDINAVICA

doi: 10.1111/j.1399-6576.2010.02225.x

Pleth variability index predicts hypotension during anesthesia induction M. TSUCHIYA, T. YAMADA and A. ASADA Department of Anesthesiology, Osaka City University Medical School, Abeno-Ku, Osaka, Japan

Background: The pleth variability index (PVI) is a new algorithm used for automatic estimation of respiratory variations in pulse oximeter waveform amplitude, which might predict fluid responsiveness. Because anesthesiainduced hypotension may be partly related to patient volume status, we speculated that pre-anesthesia PVI would be able to identify high-risk patients for significant blood pressure decrease during anesthesia induction. Methods: We measured the PVI, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) in 76 adult healthy patients under light sedation with fentanyl to obtain pre-anesthesia control values. Anesthesia was induced with bolus administrations of 1.8 mg/kg propofol and 0.6 mg/kg rocuronium. During the 3-min period from the start of propofol administration, HR, SBP, DBP, and MAP were measured at 30-s intervals. Results: HR, SBP, DBP, and MAP were significantly decreased after propofol administration by 8.5%, 33%, 23%,

and 26%, respectively, as compared with the pre-anesthesia control values. Linear regression analysis that compared pre-anesthesia PVI with the decrease in MAP yielded an r value of  0.73. Decreases in SBP and DBP were moderately correlated with pre-anesthesia PVI, while HR was not. By classifying PVI 415 as positive, a MAP decrease 425 mmHg could be predicted, with sensitivity, specificity, positive predictive, and negative predictive values of 0.79, 0.71, 0.73, and 0.77, respectively. Conclusion: Pre-anesthesia PVI can predict a decrease in MAP during anesthesia induction with propofol. Its measurement may be useful to identify high-risk patients for developing severe hypotension during anesthesia induction.

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to volume expansion.9 Furthermore, variations in arterial pulse pressure (DPP),10 vena cava diameter,11 stroke volume,12 and aortic blood flow13 have been shown to be more accurate predictors of fluid responsiveness. However, those indices are obtained by invasive means and are not universally available. Recently, variation in pulse oximeter waveform amplitude (DPOP) was shown to be strongly related to DPP, and reported to be an accurate predictor of fluid responsiveness in both mechanically ventilated and spontaneously breathing patients.14–18 In addition, the pleth variability index (PVI) is a novel software program that determines maximal and minimal plethysmographic waveform amplitudes, and then calculates the percentage difference between the two, thus serving as an automatic and continuous monitor of DPOP that is easy to use.15 Anesthesia-induced hypotension may be partly related to patient volume status. Thus, we specu-

bolus administration at anesthesia induction is sometimes associated with severe hypotension.1–6 Although ephedrine and other vasopressors can attenuate adverse hemodynamic responses,7,8 the timing of the initial hypotension before intubation requires special caution, because anesthesiologists may be distracted at that time by airway maintenance with a mask and preparation for the subsequent tracheal intubation. Thus, it is important to identify beforehand which patients are at risk for complications from such early hypotension to ensure safe conditions in the moments preceding intubation. The proper diagnosis of the degree of hypovolemia and fluid responsiveness in surgical patients is crucial for safe anesthesia management, although it is often challenging. Central venous pressure, pulmonary capillary wedge pressure, and left ventricular end-diastolic area are known to be of some value for determining which patients will respond ROPOFOL

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Accepted for publication 27 January 2010 r 2010 The Authors Journal compilation r 2010 The Acta Anaesthesiologica Scandinavica Foundation

Pleth variability index predicts hypotension

lated that PVI would be able to identify patients who are at a high risk for a significant decrease in blood pressure during anesthesia induction. To test our speculation, the present study aimed to investigate pre-anesthesia PVI levels and the magnitude of reduction in blood pressure during a routine drug administration sequence with propofol bolus administration in healthy surgical patients.

Methods Pulse oximeter oxygen saturation and calculation of the PVI We measured pulse oximeter oxygen saturation using a Masimo Radical 7 (Masimo Corp., Irvine, CA), a type of pulse oximeter equipped for determining the perfusion index (PI) and PVI. The device was attached to the index or the middle finger of the dominant arm of each patient, and PI and PVI were continuously measured. The calculation methods used for PI and PVI have been reported previously.15 In brief, PI (%) was calculated as shown below, with DC being the constant amount of light absorbed by skin, other tissues, and non-pulsatile blood, and AC being the variable amount of light absorbed by pulsating arterial inflow, which reflects the amplitude of the pulse oximeter waveform. PI ¼ ðAC=DCÞ  100 PVI (%) is a measure of the dynamic change in PI that occurs during 1 or more complete respiratory cycles, calculated as PVI ¼ ððPImax  PImin Þ=PImax Þ  100

Measurement of pre-anesthesia PVI and maximum change in blood pressure during anesthesia induction Following approval of the study protocol by our institutional Ethics Committee and receipt of written informed consent from the subjects, 77 ASA physical status I or II adult patients scheduled for elective minor non-abdominal surgery, each with good exercise tolerance (44 in a metabolic equivalent task) and no cardiopulmonary disease, including arrhythmia, hypertension, and heart failure, were included in the study. Patients with a potentially difficult airway problem were excluded from the study. All patients fasted for 11 h before surgery. Pre-anesthesia PI and PVI, and maximum changes in blood pressure and heart rate (HR)

during anesthesia induction until tracheal intubation were determined as follows: PI and PVI were monitored using a Masimo Radical 7 and hemodynamic variables using an IntelliVue MP70 (Philips Electronics Japan Corp., Tokyo, Japan). Patients received an intravenous administration of 0.2 mg/ kg of fentanyl on the operating table equipped with s a comfortable medical pad (Tempur , Tempur Japan Corp., Kobe, Japan), and then rested there while breathing 100% oxygen in a supine position and listening to calm classical music at a temperature of 25 1C for another 5 min. At the end of the 5-min rest period, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured non-invasively three times, while values for HR, PI, and PVI were also obtained three times during this period, with the mean values used as pre-anesthesia controls. Next, propofol (1.8 mg/kg) and subsequently rocuronium (0.6 mg/kg) were intravenously administrated by a bolus method within 20 s, and the patient airway was maintained with bag-mask ventilation at approximately 7 ml/kg of tidal volume under 100% oxygen breathing, in order to maintain the end-tidal carbon dioxide pressure at 35–38 mmHg. During the 3-min period from the start of propofol administration, blood pressure (SBP, DBP, and MAP) and HR were measured seven times at 30-s intervals. The differences between each value and the related pre-anesthesia control value were calculated, with the largest difference, whether positive or negative, determined as the maximal change value during the anesthesia induction period for each variable. After the 3-min analysis, the patients were intubated with the aid of 4% lidocaine for topical anesthesia of the larynx. The bispectral index (BIS) level was monitored throughout anesthesia induction, and patients in whom the BIS level did not decrease and was not maintained at o60 after propofol administration were precluded from the study protocol. Those precluded patients were then intubated with additional propofol administration. We followed the standard anesthesia induction procedure of our hospital, which consists of a short-term step of bag and mask ventilation before intubation to ensure that the airway is well maintained. In addition, we utilized standard anesthesia equipment available at our institution, although the values for PI and PVI displayed in the pulse oximeter were concealed from the view of the anesthesiologist. All data were automatically re-

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corded digitally and analyzed later by an independent party. Thus, anesthesiologists in charge were blinded to the study.

Data analysis Regression analysis and other statistical analyses were performed using Instat 3 for Macintosh (GraphPad Software Inc., San Diego, CA). All results are expressed as the mean value  standard deviation, and a P value of o0.01 was considered statistically significant. There were no data found in a literature search on the strength of correlation between change in blood pressure during anesthesia induction and pre-anesthesia PVI. A correlation hypothesis of the correlation coefficient (r) 5 0.7, which implies that about half of the variation in the dependent variable is associated with the variation in the independent variable, was assumed in this study for the purpose of sample size determination. To measure such a correlation coefficient at an a error of 0.01 and with 80% power, a sample size of 18 was required. If r 5 0.4 is assumed,19 which implies that more factors affect the regression, then a sample size of 68 would be required. Based on this power analysis, and taking into consideration the attrition rate during the study and multiplicity of influencing factors on blood pressure during anesthesia induction, 77 patients were enrolled.

Table 1 Patient demographic data. Number Gender (male/female) Age (years) Height (cm) Weight (kg) ASA status (I/II)

76 41/35 61  12 162  9 61  11 48/28

Values for age, height, and weight are expressed as the mean standard deviation.

Results One patient was excluded from this study due to a BIS level that did not decrease to o60 after propofol administration. The remaining 76 patients were investigated and their demographics are summarized in Table 1. Pre-anesthesia PVI ranged from 7 to 28, with a mean value of 16  5.5, while PI ranged from 1.1 to 8.5, with a mean value of 3.2  1.9. HR, SBP, DBP, and MAP were significantly decreased after propofol administration by 8.5%, 33%, 23%, and 26%, respectively, as compared with the pre-anesthesia controls. Precise hemodynamic data are presented in Table 2. Linear regression analysis with the least squares method between pre-anesthesia PVI (%) and the magnitude of maximum MAP change (mmHg) during anesthesia induction yielded a correlation coefficient (r) of  0.73 (Po0.01) (Table 3), and the following regression equation: Magnitude of maximum MAP change ¼ 1:0 ð95% CI; 1:20 to  0:77Þ  PVI  8:9 ð95% CI; 12:5 to  5:4Þ

Table 3 Correlation of pre-anesthesia PVI or age with the magnitude of maximum changes in heart rate and blood pressure.

Pre-anesthesia PVI Change in HR Change in SBP Change in DBP Change in MAP Age Change in HR Change in SBP Change in DBP Change in MAP

Correlation coefficient (r)

P value

0.03  0.42  0.54  0.73

0.77 o0.01 o0.01 o0.01

 0.26  0.29 0.20 0.07

0.02 0.01 0.02 0.53

PVI, pleth variability index; HR, heart rate; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure.

Table 2 Maximum changes in heart rate and blood pressure during anesthesia induction. Variable

Pre-anesthesia control

Values with the greatest absolute difference from control during anesthesia induction

P value

HR (b.p.m.) SBP (mmHg) DBP (mmHg) MAP (mmHg)

74  12 135  14 74  10 92  9

68  10 95  13 57  10 68  10

o0.01 o0.01 o0.01 o0.01

Maximum change (95% confidence interval)

Values are expressed as the mean  standard deviation. HR, heart rate; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure.

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 6.3  40.7  17.0  24.1

(  8.3–  4.3) (  43.9–  37.5) (  18.9–  15.2) (  25.8–  22.4)

Pleth variability index predicts hypotension

Fig. 2. Correlation between pre-anesthesia PI and magnitude of maximum change in MAP after propofol administration. The solid line represents the regression equation line and dotted lines on either side indicate the 95% prediction bands from regression. The regression equation is noted in the text. PI, perfusion index; MAP, mean arterial pressure; r, correlation coefficient.

Fig. 1. Correlation and linear regression of pre-anesthesia PVI with the magnitude of maximum change in HR (A) and MAP (B) after propofol administration. The regression equation for (A) is not shown, because the correlation was not significant, while that for (B) is noted in the text. Dotted lines on either side of the equation line indicate the 95% prediction band from regression. Y-axes indicate the magnitude of maximum change of each parameter. For example, in graph A, 120 b.p.m. indicates that HR maximally increased by 20 b.p.m. after propofol administration, while  20 b.p.m. indicates that HR maximally decreased by 20 b.p.m. after propofol administration. PVI, pleth variability index; HR, heart rate; MAP, mean arterial pressure; r, correlation coefficient.

where CI is the confidence interval. The magnitude of the maximum changes of SBP and DBP during anesthesia induction showed a moderately negative correlation with pre-anesthesia PVI, while HR showed no relationship with PVI (Table 3). A scatter diagram of the magnitude of the maximum changes in HR and MAP against pre-anesthesia PVI is presented in Fig. 1. The change in MAP showed a moderate correlation with pre-anesthesia PI (r 5 0.49, Po0.01) (Fig. 2), as shown by the following regression equation: Magnitude of maximum MAP change ¼ 1:9 ð95% CI; 1:10 to 2:70Þ  PI  30:4 ð95% CI; 33:4 to  27:4Þ The magnitude of the maximum change in SBP was weak and not clinically significant, and

showed a negative correlation with patient age (Table 3). In addition, none of the other parameters (HR, DBP, and MAP) showed a significant correlation with patient age. By placing patients with a pre-anesthesia PVI value 415 into the positive group and assuming that a decrease in MAP 425 mmHg was predicted, the sensitivity, specificity, positive predictive, and negative predictive values in the screening test with PVI were 0.79, 0.71, 0.73, and 0.77, respectively (Table 4).

Discussion Blood pressure and HR were significantly decreased after propofol bolus administration. It should be noted that the magnitude of changes in blood pressure and HR was unequal, in that blood pressure was decreased by 33% in SBP, 23% in DBP, and 26% in MAP as compared with the preanesthesia controls, while HR was decreased by only 8.5%. These results are quite consistent with those of previous studies, demonstrating that the major side effect of propofol, when used for anesthesia induction, on circulation is hypotension.5,20 Among SBP, DBP, and MAP changes, the change in MAP may be of most importance, because it is the most well correlated with organ perfusion. The correlation coefficient of  0.73 between preanesthesia PVI and decrease in MAP indicates that the correlation is significant, with more than half of the MAP decrease associated with pre-

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M. Tsuchiya et al. Table 4 Sensitivity, specificity, positive predictive value, and negative predictive value in the screening test for the pre-anesthesia PVI value against maximum MAP change during anesthesia induction. Observation

Sensitivity

Specificity

Positive predictive value

Negative predictive value

PVI  15 95% confidence interval

0.79 0.68–0.87

0.71 0.60–0.79

0.73 0.63–0.81

0.77 0.66–0.86

Patients with pre-anesthesia PVI 415% were classified as the positive high-risk group, while a decrease in MAP 425 mmHg during anesthesia induction was considered to be a significant decrease that could be predicted. PVI, pleth variability index; MAP, mean arterial pressure.

anesthesia PVI variation. Based on this correlation, a decrease in MAP 425 mmHg from the preanesthesia control could be predicted using a cutoff value of 15 for PVI, with a sensitivity of 0.79, a specificity of 0.71, a positive predictive value of 0.73, and a negative predictive value of 0.77. Although the level of accuracy may not be perfect for a screening test, PVI measurement has a number of advantages, such as low cost, minimal invasiveness, rapid analysis, and simplicity. Anesthesiologists are required to perform airway maintenance and tracheal intubation during this period, which can present many difficulties. Thus, an advanced understanding of the risk for significant hypotension after propofol administration with PVI may have clinical benefits to make anesthesia induction safer and more successful. In contrast to blood pressure, there was no relation between HR change and pre-anesthesia PVI. Because the change in HR was rather small, it is reasonable that PVI cannot predict that change. In mechanically ventilated patients, PVI correlates well with DPP and thus predicts fluid responsiveness.14–16 However, assessment of fluid responsiveness is not easily performed in spontaneously breathing patients, because cardiopulmonary interactions differ from those observed in mechanically ventilated patients, and the frequency of breathing and tidal volumes can vary from breath to breath. Recently, several studies have reported that DPOP and PVI may also be predictors of fluid responsiveness to a greater or a lesser degree in spontaneously breathing subjects.17,18 Thus, it is not improbable that the significance of PVI is just as valid under the present study conditions. Fluid responsiveness is dependent, at least in part, on volume status. Volume depletion increases the necessity for and responsiveness to volume loading, along with the increase in DPP and/or PVI. Considering that the risk of developing induction hypotension is associated

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with volume depletion, it is reasonable that the hypotensive effect of propofol is enhanced in patients with a large PVI value. The relationship between PVI and MAP led us to speculate that propofol induction can reveal relative hypovolemia, which is also supported from the viewpoint of the pre-anesthesia PI values. The significant correlation found between pre-anesthesia PI and maximum MAP change demonstrates that a greater decrease in MAP occurred in patients with lower PI values. Because a low PI reflects increased systemic vascular resistance, those patients may have higher vascular resistance, which would compensate for hypovolemia. Therefore, the relationship between PI and MAP is considered to provide the same interpretation as PVI and MAP measurements, as patients in a relative hypovolemic state showed greater decreases in MAP caused by propofol administration, confirming our speculation. In addition to patient volume status, it is also important to consider the effect of patient mental status when interpreting the present results. The period before anesthesia induction is a time of high anxiety for surgical patients, which might cause increases in baseline blood pressure and sympathetic tone. To minimize such adverse effects, we administered a small dose of fentanyl and allowed the patient to rest on a comfortable medical pad with classical music playing, which has been shown to reduce mental stress in the operation room.4 In spite of these calming techniques, patients might still be in a state of anxiety and an increase in baseline blood pressure may induce a greater decrease in blood pressure during anesthesia induction, while an increase in sympathetic tone might enhance DPP and, consequently, PVI as well.15,21 Thus, this anxiety-related mechanism might also contribute to the relationship between pre-anesthesia PVI and MAP decrease after propofol administration.

Pleth variability index predicts hypotension

Elderly patients have been shown to have an increased risk of hypotension during anesthesia induction.5,8 Our findings also indicate that age may be a predicting factor with regard to blood pressure decrease during anesthesia induction, although the significance of age was weaker than that of PVI. We limited the present study cohort to healthy normotensive patients with adequate exercise tolerance and the number of subjects was relatively small, which might have made the effect of age weaker. It should be noted that our subjects received not only propofol but also fentanyl and rocuronium. Because those two drugs have little or weak pharmacological effects on circulation,1,22 we considered that their administrations did not have considerable effects. In addition, the present sequence of drug administration for anesthesia induction is clinically relevant, because the combination of propofol with fentanyl and a muscle relaxant is a standard administration method for anesthesia induction, while intubation with propofol alone is much less common.4,23,24 Thus, it is considered that the present study setting was suitable for evaluation of the clinical value of PVI during routine anesthesia. Another point to consider is that blood pressure was non-invasively measured using the oscillometric principle. It has been shown that MAP measured in this way correlates well with a direct arterial approach in healthy subjects8; thus, the method is widely accepted as a reliable means for determining blood pressure in standard clinical settings as well as during anesthesia. Our finding that hypovolemic patients are more susceptible to the hypotensive effects of propofol may not be notable, as such a result would be expected, and hypotension at induction may sometimes change to normotension and even relative hypertension with subsequent tracheal intubation. However, daily clinical experience has shown that such hypotension does not always indicate adequate anesthetic depth for tracheal intubation. Forced intubation to counteract a decrease in blood pressure might lead to some deleterious complications, such as bronchospasm, arrhythmia, or extreme hypertension. Because anesthesia induction is the most important and difficult period for an anesthesiologist, it is of clinical importance to reduce every possible risk for successful and safe induction. Severe hypotension that sometimes develops after propofol administration may be part of such a risk. Importantly, our results show the

utility of a novel clinical method that is easy to perform, non-invasive, and inexpensive for predicting patients who may develop such severe hypotension within the confines of routine clinical work. However, in the variety of potential clinical circumstances, allowing patients to rest under calm conditions as in the study protocol might not be easy. Because irregularity in breathing from such causes as speaking, pauses in breathing, or overbreathing may be a major dominating factor that artificially affects the PVI value, the present study was performed in a manner to minimize this variability within our usual clinical practice protocol. Therefore, even though the measurement conditions may not be identical to ours, as long as maximum attention is paid to the conditions, in particular to prevent breathing irregularity during PVI measurement, reliable data can be obtained. In conclusion, pre-anesthesia PVI was significantly correlated with a decrease in MAP after propofol bolus administration during anesthesia induction. Therefore, its measurement may be useful to identify patients at a high risk for developing severe hypotension during anesthesia induction, which would allow anesthesiologists to adopt preventative measures to ensure greater patient safety.

References 1. Billard V, Moulla F, Bourgain JL, Megnigbeto A, Stanski DR. Hemodynamic response to induction and intubation. Propofol/fentanyl interaction. Anesthesiology 1994; 81: 1384–93. 2. Griffith KE, Joshi GP, Whitman PF, Garg SA. Priming with rocuronium accelerates the onset of neuromuscular blockade. J Clin Anesth 1997; 9: 204–7. 3. Lam AM, Pavlin EG, Visco E, Taraday J. Rocuronium versus succinylcholine-atracurium for tracheal intubation and maintenance relaxation during propofol anesthesia. J Clin Anesth 2000; 12: 449–53. 4. Tsuchiya M, Asada A, Ryo K, Noda K, Hashino T, Sato Y, Sato EF, Inoue M. Relaxing intraoperative natural sound blunts haemodynamic change at the emergence from propofol general anaesthesia and increases the acceptability of anaesthesia to the patient. Acta Anaesthesiol Scand 2003; 47: 939–43. 5. Hug CC Jr, McLeskey CH, Nahrwold ML, Roizen MF, Stanley TH, Thisted RA, Walawander CA, White PF, Apfelbaum JL, Grasela TH. Hemodynamic effects of propofol: data from over 25,000 patients. Anesth Analg 1993; 77: S21–9. 6. Reich DL, Hossain S, Krol M, Baez B, Patel P, Bernstein A, Bodian CA. Predictors of hypotension after induction of general anesthesia. Anesth Analg 2005; 101: 622–8. 7. Imran M, Khan FH, Khan MA. Attenuation of hypotension using phenylephrine during induction of anaesthesia with propofol. J Pak Med Assoc 2007; 57: 543–7.

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M. Tsuchiya et al. 8. Michelsen I, Helbo-Hansen HS, Kohler F, Lorenzen AG, Rydlund E, Bentzon MW. Prophylactic ephedrine attenuates the hemodynamic response to propofol in elderly female patients. Anesth Analg 1998; 86: 477–81. 9. Michard F, Teboul JL. Predicting fluid responsiveness in ICU patients: a critical analysis of the evidence. Chest 2002; 121: 2000–8. 10. Michard F. Changes in arterial pressure during mechanical ventilation. Anesthesiology 2005; 103: 419–28. 11. Feissel M, Michard F, Faller JP, Teboul JL. The respiratory variation in inferior vena cava diameter as a guide to fluid therapy. Intensive Care Med 2004; 30: 1834–7. 12. Reuter DA, Felbinger TW, Schmidt C, Kilger E, Goedje O, Lamm P, Goetz AE. Stroke volume variations for assessment of cardiac responsiveness to volume loading in mechanically ventilated patients after cardiac surgery. Intensive Care Med 2002; 28: 392–8. 13. Feissel M, Michard F, Mangin I, Ruyer O, Faller JP, Teboul JL. Respiratory changes in aortic blood velocity as an indicator of fluid responsiveness in ventilated patients with septic shock. Chest 2001; 119: 867–73. 14. Cannesson M, Attof Y, Rosamel P, Desebbe O, Joseph P, Metton O, Bastien O, Lehot JJ. Respiratory variations in pulse oximetry plethysmographic waveform amplitude to predict fluid responsiveness in the operating room. Anesthesiology 2007; 106: 1105–11. 15. Cannesson M, Delannoy B, Morand A, Rosamel P, Attof Y, Bastien O, Lehot JJ. Does the Pleth variability index indicate the respiratory-induced variation in the plethysmogram and arterial pressure waveforms? Anesth Analg 2008; 106: 1189–94. 16. Cannesson M, Desebbe O, Rosamel P, Delannoy B, Robin J, Bastien O, Lehot JJ. Pleth variability index to monitor the respiratory variations in the pulse oximeter plethysmographic waveform amplitude and predict fluid responsiveness in the operating theatre. Br J Anaesth 2008; 101: 200–6. 17. Delerme S, Renault R, Le Manach Y, Lvovschi V, Bendahou M, Riou B, Ray P. Variations in pulse oximetry plethysmographic waveform amplitude induced by passive leg rais-

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18.

19. 20.

21.

22.

23.

24.

ing in spontaneously breathing volunteers. Am J Emerg Med 2007; 25: 637–42. Keller G, Cassar E, Desebbe O, Lehot JJ, Cannesson M. Ability of pleth variability index to detect hemodynamic changes induced by passive leg raising in spontaneously breathing volunteers. Crit Care 2008; 12: R37. Ng KF. Changes in thrombelastograph variables associated with aging. Anesth Analg 2004; 99: 449–54. Tsuchiya M, Asada A, Maeda K, Ueda Y, Sato EF, Shindo M, Inoue M. Propofol versus midazolam regarding their antioxidant activities. Am J Respir Crit Care Med 2001; 163: 26–31. Lai HY, Yang CC, Cheng CF, Huang FY, Lee Y, Shyr MH, Kuo TB. Effect of esmolol on positive-pressure ventilationinduced variations of arterial pressure in anaesthetized humans. Clin Sci (London) 2004; 107: 303–8. McCoy EP, Maddineni VR, Elliott P, Mirakhur RK, Carson IW, Cooper RA. Haemodynamic effects of rocuronium during fentanyl anaesthesia: comparison with vecuronium. Can J Anaesth 1993; 40: 703–8. Barclay K, Eggers K, Asai T. Low-dose rocuronium improves conditions for tracheal intubation after induction of anaesthesia with propofol and alfentanil. Br J Anaesth 1997; 78: 92–4. Tsuchiya M, Sato EF, Inoue M, Asada A. Open abdominal surgery increases intraoperative oxidative stress: can it be prevented? Anesth Analg 2008; 107: 1946–52.

Address: Masahiko Tsuchiya Department of Anesthesiology Osaka City University Medical School 1-5-7 Asahi-machi Abeno-ku Osaka 545-8586 Japan e-mail: [email protected]