J Clin Monit Comput DOI 10.1007/s10877-015-9679-6
ORIGINAL RESEARCH
Tissue microcirculation measured by vascular occlusion test during anesthesia induction Tae Kyong Kim1 • Youn Joung Cho1 • Jeong Jin Min2 • John M. Murkin3 Jae-Hyon Bahk1 • Deok Man Hong1 • Yunseok Jeon1
•
Received: 5 November 2014 / Accepted: 27 February 2015 Ó Springer Science+Business Media New York 2015
Abstract Tissue microcirculation measured by vascular occlusion test is impaired during septic shock. However, it has not been investigated extensively during anesthesia induction. The aim of the study is to evaluate tissue microcirculation during anesthesia induction. We hypothesized that during anesthesia induction, tissue microcirculation measured by vascular occlusion test might be enhanced with peripheral vasodilation during anesthesia induction. We conducted a prospective observational study of 50 adult patients undergoing cardiac surgery. During anesthesia induction, we measured and analyzed tissue oxygen saturation, vascular occlusion test, cerebral oximetry, forearm-minusfingertip skin temperature gradients and hemodynamic data
Presented in part at the Society of Cardiovascular Anesthesiologists Annual Meeting, New Orleans, USA; March 2014. Drs. Yunseok Jeon and Deok Man Hong have contributed equally as the corresponding author of this manuscript.
in order to evaluate microcirculation as related to alterations in peripheral vasodilation as reflected by increased Tforearmfinger thermal gradients. During anesthesia induction, recovery slope during vascular occlusion test and cerebral oxygen saturation increased from 4.0 (1.5) to 4.7 (1.3) % s-1 (p = 0.02) and 64.0 (10.2) to 74.2 (9.2) % (p \ 0.001), respectively. Forearm-minus-fingertip skin temperature gradients decreased from 1.9 (2.9) to -1.4 (2.2) °C (p \ 0.001). There was an inverse correlation between changes in the skin temperature gradients and changes in cerebral oximetry (r = 0.33; p = 0.02). During anesthesia induction, blood pressure and forearm-minus-fingertip skin temperature gradients decrease while cerebral oximetry and vascular occlusion test recovery slope increase. These findings suggest that anesthesia induction increases tissue microcirculation with peripheral vasodilation. Keywords General anesthesia Microcirculation Intraoperative monitoring Oximetry Near-infrared spectroscopy
Trial Registration: Heart surgery registry ClnicalTrials.gov identifier: NCT01713192.
Electronic supplementary material The online version of this article (doi:10.1007/s10877-015-9679-6) contains supplementary material, which is available to authorized users. & Yunseok Jeon [email protected] 1
Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Daehakro 101, Jongno-gu, Seoul 110-744, Korea
2
Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Seoul, Korea
3
Department of Anesthesiology and Perioperative Medicine, Schulich School of Medicine, University of Western Ontario, London, ON, Canada
1 Introduction Throughout the long history of general anesthesia, the transient hypotension and underlying hemodynamics that occur during the induction of general anesthesia have been investigated extensively [1]. However, tissue microcirculation as a component of induction of general anesthesia has not been well studied. Several clinical devices can monitor tissue perfusion and microcirculation. Near-infrared spectroscopy (NIRS) technology is used to measure tissue oxygen saturation (StO2) by detecting hemoglobin oxygen saturation in vessels within the tissue illuminated by the probe. Cerebral oximetry uses
123
J Clin Monit Comput
NIRS technology to noninvasively measure regional cerebral oxygen saturation and is used in many clinical settings. NIRS technology is also being used as a method of assessing peripheral microvascular vasoreactivity. The dynamic responses of StO2 of the thenar muscle during a standardized vascular occlusion test (VOT) has been shown to reflect physiological behaviour such as microvascular reperfusion and reactivity [2, 3]. The StO2 recovery slope during VOT is interpreted as reflecting the recruitment of microvessels in response to a local hypoxic stimulus [4]. This is a prognostic factor in septic patients [5], and is strongly associated with the severity of organ dysfunction and mortality in patients with septic shock [6]. Forearm-minus-fingertip skin temperature gradients (Tforearm-finger) have also been used as an index of peripheral circulation. Previous studies reported that Tforearm-finger correlates with fingertip blood flow [7], and has been used to determine thresholds of vasoconstriction and vasodilation [8]. An increase in Tforearm-finger is known to prevent the progression of hypothermia because it reflects peripheral vasoconstriction with minimization of cutaneous heat loss [9]. We hypothesized that during anesthesia induction, tissue microcirculation measured by VOT might be enhanced with peripheral vasodilation during anesthesia induction. In this study, we measured and analyzed StO2, VOT, cerebral oximetry, Tforearm-finger and hemodynamic data during induction of anesthesia in patients undergoing cardiac surgery in order to evaluate microcirculation as related to alterations in peripheral vasodilation as reflected by increased Tforearm-finger thermal gradients.
2 Methods 2.1 Patients This prospective study was performed as a subgroup study of the heart surgery registry at Seoul National University Hospital. From July to October 2013, this registry included 113 adult patients who were admitted to the Seoul National University Hospital for heart surgery (Fig. 1). The registry includes perioperative data with intraoperative hemodynamics, skin temperature, VOT and cerebral oximetry data. It was approved by the Institutional Review Board of our hospital (IRB no. H-1207-111-419), and is in accordance with the Declaration of Helsinki. Heart surgery registry is registered at clinicalTrials.gov: NCT01713192. Written informed consents were obtained from each participant. Patients who decline to participate are excluded from the registry. Exclusion criteria of this study included; age \18 years, age [80 years, patients with an arteriovenous fistula, patients with peripheral vascular disease and patients being treated preoperatively with vasoactive drug infusion
123
Fig. 1 Flow diagram of study and patient recruitment. VOT vascular occlusion test, Tforearm-finger forearm-minus-fingertip skin temperature gradients
including norepinephrine, dopamine, phenylephrine, epinephrine and vasopressin.
2.2 Anesthesia protocol In the operating room, standard monitoring devices, including electrocardiography, non-invasive blood pressure monitors, and pulse oximetry were applied. Cerebral NIRS probes and a bispectral index monitor (BIS VISTA XP4 with bilateral sensor, Covidien, Dublin, Ireland) probe were applied to the surface of the forehead. Radial arterial catheter was placed under lidocaine local anesthesia. To differentiate the effect of anesthesia induction from that of denitrogenation on cerebral oximetry, denitrogenation with 100 % oxygen was performed until there was no further increase in cerebral oximetry. Anesthesia was induced with intravenous midazolam 0.15 mg kg-1, sufentanil 1 lg kg-1 and vecuronium 0.15 mg kg-1. After tracheal intubation, all patients were ventilated in volume controlled mode; a tidal volume of 8–10 ml kg-1 of predicted body weight, a respiratory rate adjusted to maintain an end tidal carbon dioxide tension (ETCO2) of 30–35 mmHg, an inspiratory/expiratory ratio of 1:2, and an inspiratory oxygen fraction of 0.5. Anesthesia was maintained with continuous infusions of remifentanil 6–12 ng ml-1 and propofol 1.8–2.2 lg ml-1 using a target controlled infusion device, targeting BIS values between 40 and 60. Anesthesia-related hypotension (mean blood pressure \ 60 mmHg) was treated with either ephedrine 0.1 mg kg-1 (heart rate \ 70) or phenylephrine 0.5 lg kg-1 (heart rate C 70). If blood pressure was not restored within 30 s, the regimen was repeated until the
J Clin Monit Comput
maximum doses of ephedrine 0.5 mg kg-1 or phenylephrine 4 lg kg-1. If the blood pressure was not restored by the maximum dose, vasopressin or epinephrine was administered at the anesthesiologist’s discretion. 2.3 Skin temperature Skin-temperature probes (400 series, GE Healthcare, Helsinki, Finland) were placed on the surface of the forearm (Tforearm, halfway between the elbow and the wrist) and the middle fingertip (Tfinger, opposite the nail bed). Tforearmfinger were calculated and recorded. The operating room temperature was maintained at 22–24 °C. Skin temperature recording was started 10 min prior to induction of anesthesia and continued at 1-min intervals. 2.4 Vascular occlusion test A NIRS sensor was placed on the contralateral thenar eminence and a StO2 tissue oxygenation monitor (InSpectraTM StO2 tissue oxygenation monitor model 650; Hutchinson Technology Inc., Hutchinson, MN, USA) was used to measure StO2 continuously and to assess the dynamic changes in StO2. A conventional pneumatic blood pressure cuff was placed around the upper arm and baseline blood pressure was measured. VOT was performed by rapidly inflating (within 5 s) a pneumatic cuff to 50 mmHg above the systolic blood pressure. It remained inflated until the StO2 decreased to 40 %, at which time, the cuff was rapidly deflated (within 1 s) to 0 mmHg [3] (Fig. 2). A VOT was performed two times (at T1 and T2) by a single researcher (T.K.K.). First VOT was performed prior to the induction of anesthesia before applying oxygen (T1, Fig. 3). After administering induction drug, Tforearm-finger
was continuously monitored and calculated by a researcher (T.K.K.). T0 was defined as the start of anesthetic induction with midazolam, vecuronium, and sufentanil intravenous administration. The threshold for peripheral vasoconstriction was defined as T2, the inflection point at which a successive rapid increase in Tforearm-finger occurred [10]. At this T2 point, a second VOT was performed to quantify changes in microcirculatory vasoreactivity (Fig. 3). The second VOT was performed at 10.7 (4.8) min after T0. VOT was performed after a 3-min stabilization period. Stability was defined as StO2 variation \2 % over 30 s [3]. The StO2 values were recorded continuously on the monitoring device at 2-s intervals and were analyzed retrospectively using InSpectra Analysis software (InSpectra Analysis Program version 4.03; Hutchinson Technology Inc.). StO2 baseline average, VOT-derived occlusion phase parameters and recovery phase parameters were recorded. Peripheral perfusion was also evaluated by tissue hemoglobin index (THI) derived from the StO2 algorithm of the NIRS monitor. The amount of tissue hemoglobin present is influenced by blood hemoglobin concentration and microvasculature volume. THI provides a quantified value that corresponds to the amount of hemoglobin present within the volume of tissue [11]. 2.5 Cerebral oximetry Prior to induction of anesthesia, two cerebral oximetry (INVOS 5100Ò Cerebral Oximeter, Somanetics, Covidien) sensors were applied on the surface of the forehead on both the left and right sides after cleaning the skin with an alcohol swab. Regional cerebral oxygen saturation data were collected and continuously recorded at 30-s intervals using NIRS. Measurements began approximately 3 min after the sensors were applied. The averages of left and right values were used for data analysis. 2.6 Hemodynamic data
Fig. 2 Tissue oxygen saturation during a vascular occlusion test. StO2 tissue oxygen saturation
Cardiac output was measured noninvasively using a radial artery derived FloTrac sensor (Edwards Lifesciences, Irvine, CA, USA) connected to EV1000 monitor (EV1000TM; Edwards Lifesciences, Irvine, CA, USA) and corrected for body surface area to give the cardiac index. Cardiac index data were recorded at 20-s intervals. Blood pressure, heart rate and electrocardiography were monitored continuously during the study using the patient monitor (Solar 8000M, GE, Milwaukee, WI, USA). The pressure transducer was leveled to the mid-axillary line and the patient was in a neutral position lying flat on the bed during the study period.
123
J Clin Monit Comput
Fig. 3 Timeline for the study protocol. The second VOT was performed at 10.7 (4.8) min after start of anesthesia induction. VOT vascular occlusion test, T1 first VOT before applying oxygen,
T2 s VOT when forearm-minus-fingertip skin temperature gradients began to increase. T0 the start of anesthetic induction by the midazolam, vecuronium, and sufentanil intravenous administration
2.7 Statistical analysis
analyzed, at one or more timepoint, VOT data from 16 patients was not analysable because of an indistinct StO2 graph shape or data loss, the FloTrac-derived cardiac index from 14 patients was not analysable due to a data collection problem, and Tforearm-finger from two patients could not be analyzed due to data loss. None of the patients had more than two missing variables concurrently. Patient demographic data are shown in Table 1. During the study period, there was no episode of hypoxemia or hypercarbia monitored by pulse oximetry and ETCO2, respectively. Cerebral oximetry, ETCO2, cardiac index, heart rate, mean blood pressure, Tforearm-finger averaged over 1-min intervals are shown in Fig. 4a–f, respectively.
The primary end-point was VOT recovery slope at T2. One study reported that baseline recovery slope was 5.1 (3.89–5.53) % s-1 in patients undergoing major abdominal surgery [6]. We hypothesized that a 20 % increase in recovery slope at T2 was clinically relevant. A sample size of 32 patients was needed to detect a difference from baseline with a type I error of 0.05 and a power of 0.9. Considering possible dropouts, we chose to examine 50 patients. As our goal was to evaluate the effect of anesthesia induction on cerebral and tissue oxygenation, and since the maximum changes occurred within 20 min after anesthesia induction, consequently differences between maximal values within 20 min and at T0 for Tforearm-finger, cerebral oximetry, mean blood pressure, heart rate and cardiac index were assessed using a paired t test and Pearson’s correlations were used to test the relationship between them. Non-analysable data or data loss were excluded from correlation analyses. Mean values of StO2 and THI parameters derived from VOT at T1 and T2 were compared using a paired t test. Tforearmfinger, cerebral oximetry, mean blood pressure, heart rate and cardiac index were analyzed using repeated-measures analysis of variance at T0 and every minute for 60 min. All data were collected by dedicated researchers who were blinded to the specifics of the study. Results are expressed as the numbers of patients, the means (SD). p \ 0.05 was considered to indicate statistical significance. Statistical analyses were performed using SPSS 18.0 (SPSS Institute, Chicago, IL, USA).
3.2 Skin temperature Following administration of the intravenous induction drug, Tforearm-finger rapidly decreased from 1.9 (2.9) to -1.4 (2.2) °C (p \ 0.001). After 10.7 (4.8) min, Tforearm-finger decrease stopped and then began to rise. The pattern of Tforearm-finger during the interval following induction of general anesthesia is comparable with previous reports [12]. Table 1 Baseline characteristics Characteristic
Value
Number of patients
50
Age (year)
60.3 (15.0)
Sex (Male/female)
27 (54.0 %)/23 (46.0 %)
Weight (kg)
60.4 (11.7)
Height (cm)
162.0 (9.5)
3 Results
Body mass index
23.0 (3.8)
Diabetes
16 (32.0 %)
3.1 Patients’ characteristics
Hypertension
23 (46.0 %)
Hyperlipidemia
2 (4.0 %)
From July to October 2013, 113 patients were recruited for heart surgery registry. Among these 113 patients, two patients met the exclusion criteria for this subgroup study (patients being treated with vasoactive drug infusion). For this subgroup study, two specific measurements (continuous skin temperature monitoring at two sites and one more VOT during anesthesia induction) were needed, but, these were not available in 61 of the 113 patients due to equipment or personnel problems. Finally, 50 patients were enrolled and analyzed (Fig. 1). Among the 50 patients
123
Cerebrovascular disease
6 (12.0 %)
Beta blocker
13 (26.0 %)
Calcium channel blocker
9 (18.0 %)
Diuretics
16 (32.0 %)
Angiotension receptor blocker Angiotension-converting-enzyme inhibitor
8 (16 %) 3 (6 %)
Statin
11 (22.0 %)
Preoperative ejection fraction (%)
57.7 (11.7)
Data are expressed as a mean (SD) or number (%)
J Clin Monit Comput Fig. 4 Cerebral oximetry, end tidal carbon dioxide tension, cardiac index, forearm-minusfingertip temperature gradients, heart rate, and mean blood pressure averaged over 1-min intervals. Asterisks indicate significant change at individual time point compared with values at time 0 (repeatedmeasures analysis of variance, *p \ 0.05). T0: the start of anesthetic induction by the midazolam, vecuronium, and sufentanil intravenous administration. Values are shown as mean ± SE. ETCO2 end tidal carbon dioxide tension, Tforearm-finger forearmminus-fingertip temperature gradients
123
J Clin Monit Comput
3.3 Vascular occlusion test We performed VOT twice at T1 and T2. Dynamic parameters of the StO2 derived from VOT are presented in Table 2. VOT occlusion slope increased from -10.5 (4.5) % min-1 at T1 to -7.9 (2.8) % min-1 at T2 (p = 0.004). VOT recovery slope increased from 4.0 (1.5) % s-1 at T1 to 4.7 (1.3) % s-1 at T2 (p = 0.02). The dynamic parameters of THI did not reveal any significant change (Online Resource 1, which are dynamic parameters of THI and Online Resource 2, which are description of VOT parameters). The measurements of individual changes in VOT occlusion slope and recovery slope at T1 and T2 for each patient are presented in Fig. 5. A box plot of VOT occlusion slope and recovery slope are presented in Fig. 6. 3.4 Cerebral oximetry Following administration of the intravenous induction drug, cerebral oximetry began to rise rapidly, increasing from 64.0 (10.2) to 74.2 (9.2) % (p \ 0.001). After 7.1 (3.4) min, the increasing phase ended and cerebral oximetry decreased slowly and then stabilized at 59.2 (8.5) %. 3.5 Hemodynamic data Following administration of the intravenous induction drug, the cardiac index decreased gradually from 3.6 (1.8) to 2.2 (0.9) l min-1 m-2 (p \ 0.001). Heart rate also Table 2 Dynamic parameters of tissue oxygen saturation derived from vascular occlusion test
decreased from 74.8 (15.6) to 58.8 (12.8) (p \ 0.001). Mean blood pressure decreased from 90.2 (12.2) to 59.3 (11.3) mmHg (p \ 0.001). Mean blood pressure and cardiac index prior to time 0 are not shown in Fig. 4, because arterial line was generally established just prior to the start of anesthetic induction. Correlation analysis was performed between maximum changes of Tforearm-finger, cerebral oximetry, cardiac index, mean blood pressure, and VOT recovery slope within 20 min following induction of anesthesia. There was an inverse correlation between changes in Tforearm-finger and changes in cerebral oximetry (r = 0.33; p = 0.02) (Table 3).
4 Discussion The main finding of this study was that during anesthesia induction, blood pressure and Tforearm-finger decrease while cerebral oximetry and VOT recovery slope increase. The anesthetic-induced inhibition of thermoregulatory vasoconstriction is greatest when Tforearm-finger reaches the point of inflection [10, 13]. Therefore, increased VOT recovery slope at the Tforearm-finger inflection point reflects increased tissue microcirculation with peripheral vasodilation following anesthesia induction. Vasodilation does not always increase tissue perfusion. During septic shock, even with vasodilation, microcirculation is impaired [14]. In the study by Skarda [2], VOT recovery slope decreased in patients with severe sepsis. In T1 (n = 34)
T2 (n = 34)
82.6 (6.3)
83.5 (4.3)
-10.5 (4.5)
p value
Baseline parameter Baseline average (%)
0.40
Ischemia parameter Occlusion slope (% min-1)
-7.9 (2.8)
0.004
0.97 (0.38)
0.91 (0.19)
0.05
Occlusion slope tissue hemoglobin index adjusted
-137.0 (56.9)
-102.6 (41.5)
0.003
Ischemia area (% min)*
-107.1 (68.1)
-123.0 (77.6)
0.27
Occlusion slope fit (R2)
Recovery parameter Recovery slope (% sec-1) Recovery slope fit (R2)
4.0 (1.5)
4.7 (1.3)
0.02
0.98 (0.04)
0.99 (0.01)
0.10
Baseline recovery time (seconds after deflation)
19.2 (15.9)
14.1 (6.2)
0.09
Peak recovery time (seconds after deflation)
44.9 (48.0)
31.3 (12.3)
0.10
Hyperemia recovery time (seconds after deflation)
201.2 (118.6)
208.2 (108.6)
0.81
Baseline recovery area (% min)*
-5.6 (2.7)
-5.3 (2.3)
0.60
Hyperemia recovery area (% min)*
22.1 (21.2)
20.9 (12.1)
0.81
Data are expressed as a mean (SD) T1 first vascular occlusion test before applying oxygen, T2 s vascular occlusion test when forearm-minusfingertip skin temperature gradients began to increase * It is the integrated area of the graph for the time interval. Thus, it should be (% x min) or (%.min) for Ischemia area, Baseline recovery area, and Hyperemia recovery area (multiplication)
123
J Clin Monit Comput
Fig. 5 Individual changes in vascular occlusion test occlusion slope (a) and recovery slope (b) for every patient. VOT vascular occlusion test, T1 first VOT before applying oxygen, T2 s VOT when forearm-minus-fingertip skin temperature gradients began to increase
Fig. 6 Box plot of vascular occlusion test occlusion slope (a) and recovery slope (b). Occlusion slope increased from -10.5 (4.5) % min-1 at T1 to -7.9 (2.8) % min-1 at T2 (p = 0.004). Recovery slope increased from 4.0 (1.5) % s-1 at T1 to 4.7 (1.3) % s-1 at T2 (p = 0.02). Boxes represent the interquartile range
and the line inside represents the median. Whiskers represent 10/90 % quantiles and black dots represent outliers beyond the whiskers. VOT vascular occlusion test, T1 first VOT before applying oxygen, T2 s VOT when forearm-minus-fingertip skin temperature gradients began to increase
contrast, VOT recovery slope increased in the current study. VOT recovery slope is thought to reflect local tissue perfusion adequacy or local cardiovascular reserve because it represents the time required to wash out stagnant deoxygenated blood by oxygenated arterial blood during reperfusion [3, 4]. VOT recovery slope correlates with peripheral perfusion parameters but is independent of the systemic hemodynamic parameters in critically ill patients [15]. Since low StO2 and decreased VOT recovery slope have been associated with low peripheral flow index, indicating either vasoconstriction and/or impairment of microcirculatory flow [16], the increase in recovery slope and unchanged StO2 observed in this study following the
induction of anesthesia indicates local vasodilation and increased microcirculatory flow. In this study, VOT occlusion slope increased significantly following anesthesia induction, which suggests a decrease in the local metabolic rate since it is related to the rate of tissue oxygen consumption [3]. Thenar tissue metabolic rate may decrease because of the use of the neuromuscular blocking drug vecuronium during induction [17] or because of the preconditioning effect of VOT performed prior to anesthesia induction [18]. Cerebral oximetry measures the balance between cerebral oxygen supply and demand and correlates with changes in the cerebral blood flow when the arterial oxygen
123
J Clin Monit Comput Table 3 Correlation coefficients among the changes in forearm-minus-fingertip temperature gradients, cerebral oximetry, cardiac index, mean blood pressure, and vascular occlusion test recovery slope D Mean blood pressure (mmHg)
D VOT recovery slope (% s-1)
0.087
-0.102
0.075
0.62 35
0.50 47
0.68 33
D Cerebral oximetry (%)
D Cardiac index (l min-1 m-2)
1
0.327
48
0.02 48
D Tforearm-finger (°C) D Tforearm-finger (°C) r p n
D Cerebral oximetry (%) r
0.327
p
0.02
n
48
1
-0.022
-0.045
-0.319
0.90
0.76
0.06
50
36
48
35
1
D Cardiac index (l min-1 m-2) r
0.087
-0.022
p
0.62
0.90
n
35
36
0.141
-0.240
0.42
0.24
36
35
26
0.141
1
-0.226
D Mean blood pressure (mmHg) r
-0.102
-0.045
p
0.50
0.76
0.42
n
47
48
35
48
33
0.21
D VOT recovery slope (% s-1) r p
0.075 0.68
-0.319 0.06
-0.240 0.24
-0.226 0.21
1
n
33
35
26
33
35
Tforearm-finger forearm-minus-fingertip skin temperature gradients, VOT vascular occlusion test, D peak value after induction minus baseline value
saturation and cerebral oxygen consumption are constant [19]. Midazolam [20] and sufentanil [21] are known to reduce cerebral blood flow and cerebral metabolic rates by cerebral blood flow-metabolism coupling. An increase in cerebral oximetry despite decreased cerebral blood flow implies that metabolic rate decreased more than cerebral blood flow decreased [22], which may explain the mechanism by which cerebral oximetry values increased following the induction of anesthesia in this study. In the current study, the increase in cerebral oximetry was not maintained; rather it decreased and was stabilized within 15 min following a bolus administration of induction anesthetics (Fig. 4a). However, in the current study, BIS level decreased after administration of induction anesthetics and maintained a plateau throughout the induction period of over 30 min (Online Resource 3, typical pattern of BIS during induction of anesthesia) which was inconsistent with the pattern of cerebral oximetry (Fig. 4a). Since BIS correlates linearly with the magnitude of the cerebral metabolic reduction during anesthesia [23], decreased cerebral metabolic rate cannot solely explain the increase in cerebral oximetry. Another possibility is that cerebral oximetry could reflect increased cerebral microcirculatory flow following induction of anesthesia as identified in peripheral tissues using VOT in this study. Cerebral arteries are
123
abundantly innervated by sympathetic fibers [24], and induction anesthetics could induce a sympatholytic effect and cerebral arteriolar vasodilation. However, it is difficult to be concluded in the present study and further study is needed. In this study, despite significant decreases in the arterial perfusion pressure, oxygenation of both the brain and peripheral tissue as measured by cerebral oximetry and StO2 monitor increased during anesthesia induction. These findings suggest that anesthesia induction increased the tissue microcirculation. In this study, the lowest recorded mean arterial pressure was [65 mmHg; this might provide enough perfusion pressure to allow peripheral autoregulation. Note that this study was not planned to evaluate the clinical outcome. Additional studies are needed to evaluate the risk of anesthesia-induced hypotension. There were several limitations to this study. First, several factors which could affect cerebral oximetry could not be sufficiently controlled in this study. Cerebral oximetry values may be influenced by extracerebral tissue that can change the cerebral oxygen saturation by a variable amount [25], and StO2 has similar limitations [26]. It is thus possible that the increases in cerebral oximetry values that we observed were induced by alterations in extracerebral tissue oxygenation. Moreover, phenylephrine has been shown to reduce cerebral oximetry values in anesthetized patients
J Clin Monit Comput
[27]. In our study, phenylephrine was used in seven patients during anesthesia induction (20 min after T0) and this could have affected the cerebral oximetry values. Also, cerebral blood flow is sensitive to changes in PaCO2 and there was a period of hypoventilation during endotracheal intubation that may have increased PaCO2 concentrations. In the current study mean ETCO2 values were stable and did not exceed 40 mmHg at any time point. However, reliable ETCO2 monitoring was not available until after endotracheal intubation (Fig. 4b). Second, VOT has not been standardized with regard to the site of measurement, ischemic threshold, probe size and time interval between tests [28]. Moreover, during this study we found that the StO2 slope did not show clear linearity in 16 patients. These VOT data were not analyzed. Previous reports suggest that voluntary thenar muscle activity or technical aspects of the sampling can affect the potential for VOT non-linearity [3]. Third, there was missing data for FloTrac-derived cardiac index in 14 patients due to a data storage problem. Moreover, the reliability of the FloTrac sensor is still under debate [29]. Fourth, not only the brain but also the heart may be the organs most prone to ischemic injury during hypotension. While we did not specifically measure myocardial oxygenation in this study, we did not find any signs of myocardial ischemia on electrocardiography or transesophageal echocardiography. Fifth, we did not measure central temperature during the induction period. Finally, midazolam and sufentanil were used as induction anesthetics in the current study. Caution should be made in generalizing the outcomes to other induction anesthetics. In conclusion, during anesthesia induction, blood pressure and Tforearm-finger decrease while cerebral oximetry and VOT recovery slope increase. These findings suggest that anesthesia induction increases tissue microcirculation with peripheral vasodilation. Acknowledgments We thank to Medical Research Collaborating Center (MRCC) of Seoul National University Hospital (Seoul National University Hospital, Seoul, Korea) for the statistical assistance and supervision. None of the authors has a personal financial interest in this research. Conflict of interest Hippo Medical Company (Seoul, Korea) and Hutchinson (MN, USA) provided the InSpectraTM StO2 tissue oxygenation monitor during this study.
References 1. Alecu C, Cuignet-Royer E, Mertes PM, Salvi P, Vespignani H, Lambert M, Bouaziz H, Benetos A. Pre-existing arterial stiffness can predict hypotension during induction of anaesthesia in the elderly. Br J Anaesth. 2010;105(5):583–8. 2. Skarda DE, Mulier KE, Myers DE, Taylor JH, Beilman GJ. Dynamic near-infrared spectroscopy measurements in patients with severe sepsis. Shock. 2007;27(4):348–53.
3. Go´mez H, Torres A, Polanco P, Kim HK, Zenker S, Puyana JC, Pinsky MR. Use of non-invasive NIRS during a vascular occlusion test to assess dynamic tissue O2 saturation response. Intensive Care Med. 2008;34(9):1600–7. 4. De Blasi RA, Palmisani S, Alampi D, Mercieri M, Romano R, Collini S, Pinto G. Microvascular dysfunction and skeletal muscle oxygenation assessed by phase-modulation near-infrared spectroscopy in patients with septic shock. Intensive Care Med. 2005;31(12):1661–8. 5. Creteur J, Carollo T, Soldati G, Buchele G, De Backer D, Vincent J-L. The prognostic value of muscle StO2 in septic patients. Intensive Care Med. 2007;33(9):1549–56. 6. Futier E, Christophe S, Robin E, Petit A, Pereira B, Desbordes J, Bazin J-E, Vallet B. Use of near-infrared spectroscopy during a vascular occlusion test to assess the microcirculatory response during fluid challenge. Crit Care. 2011;15:R214. 7. Rubinstein EH, Sessler DI. Skin-surface temperature gradients correlate with fingertip blood flow in humans. Anesthesiology. 1990;73(3):541–5. 8. House JR, Tipton MJ. Using skin temperature gradients or skin heat flux measurements to determine thresholds of vasoconstriction and vasodilatation. Eur J Appl Physiol. 2002;88(1–2): 141–5. 9. Kurz A, Sessler DI, Christensen R, Dechert M. Heat balance and distribution during the core-temperature plateau in anesthetized humans. Anesthesiology. 1995;83(3):491–9. 10. Nakajima Y, Mizobe T, Matsukawa T, Sessler DI, Kitamura Y, Tanaka Y. Thermoregulatory response to intraoperative headdown tilt. Anesth Analg. 2002;94(1):221–6. 11. Myers D, McGraw M, George M, Mulier K, Beilman G. Tissue hemoglobin index: a non-invasive optical measure of total tissue hemoglobin. Crit Care. 2009;13(Suppl 5):S2. 12. Nakajima Y, Mizobe T, Takamata A, Tanaka Y. Baroreflex modulation of peripheral vasoconstriction during progressive hypothermia in anesthetized humans. Am J Physiol Regul Integr Comp Physiol. 2000;279(4):R1430–6. 13. Ikeda T, Sessler DI, Kikura M, Kazama T, Ikeda K, Sato S. Less core hypothermia when anesthesia is induced with inhaled sevoflurane than with intravenous propofol. Anesth Analg. 1999; 88(4):921–4. 14. De Backer D, Creteur J, Preiser J-C, Dubois M-J, Vincent J-L. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med. 2002;166(1):98–104. 15. Lima A, van Bommel J, Sikorska K, van Genderen M, Klijn E, Lesaffre E, Ince C, Bakker J. The relation of near-infrared spectroscopy with changes in peripheral circulation in critically ill patients. Crit Care Med. 2011;39(7):1649–54. 16. Lima A, Ince C, Bakker J. Use of tissue oxygenation saturation in association with skin temperature as an indicator of the peripheral tissue perfusion in critically ill patients. Crit Care. 2009;13:1–1. 17. Irish CL, Murkin JM, Cleland A, MacDonald JL, Mayer R. Neuromuscular blockade significantly decreases systemic oxygen consumption during hypothermic cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 1991;5(2):132–4. 18. Cortes D, Puflea F, Donadello K, de Backer D, Vincent J, Creteur J. Effects of rapid repetition of a vascular occlusion test on nearinfrared spectroscopy-derived variables in healthy subjects and in critically ill patients. Crit Care. 2013;17(Suppl 3):P2. 19. Wong FY, Nakamura M, Alexiou T, Brodecky V, Walker AM. Tissue oxygenation index measured using spatially resolved spectroscopy correlates with changes in cerebral blood flow in newborn lambs. Intensive Care Med. 2009;35(8):1464–70. 20. Baughman VL, Hoffman WE, Miletich DJ, Albrecht RF. Cerebral metabolic depression and brain protection produced by midazolam and etomidate in the rat. J Neurosurg Anesthesiol. 1989;1(1):22–8.
123
J Clin Monit Comput 21. Stephan H, Groger P, Weyland A, Hoeft A, Sonntag H. The effect of sufentanil on cerebral blood flow, cerebral metabolism and the CO2 reactivity of the cerebral vessels in man. Anaesthesist. 1991;40(3):153–60. 22. Lovell AT, Owen-Reece H, Elwell CE, Smith M, Goldstone JC. Continuous measurement of cerebral oxygenation by near infrared spectroscopy during induction of anesthesia. Anesth Analg. 1999;88(3):554–8. 23. Alkire MT. Quantitative EEG correlations with brain glucose metabolic rate during anesthesia in volunteers. Anesthesiology. 1998;89(2):323–33. 24. Busija D, Heistad D. Effects of activation of sympathetic nerves on cerebral blood flow during hypercapnia in cats and rabbits. J Physiol. 1984;347(1):35–45. 25. Sørensen H, Secher NH, Siebenmann C, Nielsen HB, Kohl-Bareis M, Lundby C, Rasmussen P. Cutaneous vasoconstriction affects near-infrared spectroscopy determined cerebral oxygen saturation
123
26.
27.
28.
29.
during administration of norepinephrine. Anesthesiology. 2012; 117(2):263–70. Creteur J, Neves AP, Vincent J-L. Near-infrared spectroscopy technique to evaluate the effects of red blood cell transfusion on tissue oxygenation. Crit Care. 2009;13(Suppl 5):S11. Meng L, Cannesson M, Alexander B, Yu Z, Kain Z, Cerussi A, Tromberg B, Mantulin W. Effect of phenylephrine and ephedrine bolus treatment on cerebral oxygenation in anaesthetized patients. Br J Anaesth. 2011;107(2):209–17. Go´mez H, Mesquida J, Simon P, Kim HK, Puyana JC, Ince C, Pinsky MR. Characterization of tissue oxygen saturation and the vascular occlusion test: influence of measurement sites, probe sizes and deflation thresholds. Crit Care. 2009;13(Suppl 5):S3. Monnet X, Anguel N, Jozwiak M, Richard C, Teboul J-L. Thirdgeneration FloTrac/Vigileo does not reliably track changes in cardiac output induced by norepinephrine in critically ill patients. Br J Anaesth. 2012;108(4):615–22.
ORIGINAL RESEARCH
Tissue microcirculation measured by vascular occlusion test during anesthesia induction Tae Kyong Kim1 • Youn Joung Cho1 • Jeong Jin Min2 • John M. Murkin3 Jae-Hyon Bahk1 • Deok Man Hong1 • Yunseok Jeon1
•
Received: 5 November 2014 / Accepted: 27 February 2015 Ó Springer Science+Business Media New York 2015
Abstract Tissue microcirculation measured by vascular occlusion test is impaired during septic shock. However, it has not been investigated extensively during anesthesia induction. The aim of the study is to evaluate tissue microcirculation during anesthesia induction. We hypothesized that during anesthesia induction, tissue microcirculation measured by vascular occlusion test might be enhanced with peripheral vasodilation during anesthesia induction. We conducted a prospective observational study of 50 adult patients undergoing cardiac surgery. During anesthesia induction, we measured and analyzed tissue oxygen saturation, vascular occlusion test, cerebral oximetry, forearm-minusfingertip skin temperature gradients and hemodynamic data
Presented in part at the Society of Cardiovascular Anesthesiologists Annual Meeting, New Orleans, USA; March 2014. Drs. Yunseok Jeon and Deok Man Hong have contributed equally as the corresponding author of this manuscript.
in order to evaluate microcirculation as related to alterations in peripheral vasodilation as reflected by increased Tforearmfinger thermal gradients. During anesthesia induction, recovery slope during vascular occlusion test and cerebral oxygen saturation increased from 4.0 (1.5) to 4.7 (1.3) % s-1 (p = 0.02) and 64.0 (10.2) to 74.2 (9.2) % (p \ 0.001), respectively. Forearm-minus-fingertip skin temperature gradients decreased from 1.9 (2.9) to -1.4 (2.2) °C (p \ 0.001). There was an inverse correlation between changes in the skin temperature gradients and changes in cerebral oximetry (r = 0.33; p = 0.02). During anesthesia induction, blood pressure and forearm-minus-fingertip skin temperature gradients decrease while cerebral oximetry and vascular occlusion test recovery slope increase. These findings suggest that anesthesia induction increases tissue microcirculation with peripheral vasodilation. Keywords General anesthesia Microcirculation Intraoperative monitoring Oximetry Near-infrared spectroscopy
Trial Registration: Heart surgery registry ClnicalTrials.gov identifier: NCT01713192.
Electronic supplementary material The online version of this article (doi:10.1007/s10877-015-9679-6) contains supplementary material, which is available to authorized users. & Yunseok Jeon [email protected] 1
Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Daehakro 101, Jongno-gu, Seoul 110-744, Korea
2
Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Seoul, Korea
3
Department of Anesthesiology and Perioperative Medicine, Schulich School of Medicine, University of Western Ontario, London, ON, Canada
1 Introduction Throughout the long history of general anesthesia, the transient hypotension and underlying hemodynamics that occur during the induction of general anesthesia have been investigated extensively [1]. However, tissue microcirculation as a component of induction of general anesthesia has not been well studied. Several clinical devices can monitor tissue perfusion and microcirculation. Near-infrared spectroscopy (NIRS) technology is used to measure tissue oxygen saturation (StO2) by detecting hemoglobin oxygen saturation in vessels within the tissue illuminated by the probe. Cerebral oximetry uses
123
J Clin Monit Comput
NIRS technology to noninvasively measure regional cerebral oxygen saturation and is used in many clinical settings. NIRS technology is also being used as a method of assessing peripheral microvascular vasoreactivity. The dynamic responses of StO2 of the thenar muscle during a standardized vascular occlusion test (VOT) has been shown to reflect physiological behaviour such as microvascular reperfusion and reactivity [2, 3]. The StO2 recovery slope during VOT is interpreted as reflecting the recruitment of microvessels in response to a local hypoxic stimulus [4]. This is a prognostic factor in septic patients [5], and is strongly associated with the severity of organ dysfunction and mortality in patients with septic shock [6]. Forearm-minus-fingertip skin temperature gradients (Tforearm-finger) have also been used as an index of peripheral circulation. Previous studies reported that Tforearm-finger correlates with fingertip blood flow [7], and has been used to determine thresholds of vasoconstriction and vasodilation [8]. An increase in Tforearm-finger is known to prevent the progression of hypothermia because it reflects peripheral vasoconstriction with minimization of cutaneous heat loss [9]. We hypothesized that during anesthesia induction, tissue microcirculation measured by VOT might be enhanced with peripheral vasodilation during anesthesia induction. In this study, we measured and analyzed StO2, VOT, cerebral oximetry, Tforearm-finger and hemodynamic data during induction of anesthesia in patients undergoing cardiac surgery in order to evaluate microcirculation as related to alterations in peripheral vasodilation as reflected by increased Tforearm-finger thermal gradients.
2 Methods 2.1 Patients This prospective study was performed as a subgroup study of the heart surgery registry at Seoul National University Hospital. From July to October 2013, this registry included 113 adult patients who were admitted to the Seoul National University Hospital for heart surgery (Fig. 1). The registry includes perioperative data with intraoperative hemodynamics, skin temperature, VOT and cerebral oximetry data. It was approved by the Institutional Review Board of our hospital (IRB no. H-1207-111-419), and is in accordance with the Declaration of Helsinki. Heart surgery registry is registered at clinicalTrials.gov: NCT01713192. Written informed consents were obtained from each participant. Patients who decline to participate are excluded from the registry. Exclusion criteria of this study included; age \18 years, age [80 years, patients with an arteriovenous fistula, patients with peripheral vascular disease and patients being treated preoperatively with vasoactive drug infusion
123
Fig. 1 Flow diagram of study and patient recruitment. VOT vascular occlusion test, Tforearm-finger forearm-minus-fingertip skin temperature gradients
including norepinephrine, dopamine, phenylephrine, epinephrine and vasopressin.
2.2 Anesthesia protocol In the operating room, standard monitoring devices, including electrocardiography, non-invasive blood pressure monitors, and pulse oximetry were applied. Cerebral NIRS probes and a bispectral index monitor (BIS VISTA XP4 with bilateral sensor, Covidien, Dublin, Ireland) probe were applied to the surface of the forehead. Radial arterial catheter was placed under lidocaine local anesthesia. To differentiate the effect of anesthesia induction from that of denitrogenation on cerebral oximetry, denitrogenation with 100 % oxygen was performed until there was no further increase in cerebral oximetry. Anesthesia was induced with intravenous midazolam 0.15 mg kg-1, sufentanil 1 lg kg-1 and vecuronium 0.15 mg kg-1. After tracheal intubation, all patients were ventilated in volume controlled mode; a tidal volume of 8–10 ml kg-1 of predicted body weight, a respiratory rate adjusted to maintain an end tidal carbon dioxide tension (ETCO2) of 30–35 mmHg, an inspiratory/expiratory ratio of 1:2, and an inspiratory oxygen fraction of 0.5. Anesthesia was maintained with continuous infusions of remifentanil 6–12 ng ml-1 and propofol 1.8–2.2 lg ml-1 using a target controlled infusion device, targeting BIS values between 40 and 60. Anesthesia-related hypotension (mean blood pressure \ 60 mmHg) was treated with either ephedrine 0.1 mg kg-1 (heart rate \ 70) or phenylephrine 0.5 lg kg-1 (heart rate C 70). If blood pressure was not restored within 30 s, the regimen was repeated until the
J Clin Monit Comput
maximum doses of ephedrine 0.5 mg kg-1 or phenylephrine 4 lg kg-1. If the blood pressure was not restored by the maximum dose, vasopressin or epinephrine was administered at the anesthesiologist’s discretion. 2.3 Skin temperature Skin-temperature probes (400 series, GE Healthcare, Helsinki, Finland) were placed on the surface of the forearm (Tforearm, halfway between the elbow and the wrist) and the middle fingertip (Tfinger, opposite the nail bed). Tforearmfinger were calculated and recorded. The operating room temperature was maintained at 22–24 °C. Skin temperature recording was started 10 min prior to induction of anesthesia and continued at 1-min intervals. 2.4 Vascular occlusion test A NIRS sensor was placed on the contralateral thenar eminence and a StO2 tissue oxygenation monitor (InSpectraTM StO2 tissue oxygenation monitor model 650; Hutchinson Technology Inc., Hutchinson, MN, USA) was used to measure StO2 continuously and to assess the dynamic changes in StO2. A conventional pneumatic blood pressure cuff was placed around the upper arm and baseline blood pressure was measured. VOT was performed by rapidly inflating (within 5 s) a pneumatic cuff to 50 mmHg above the systolic blood pressure. It remained inflated until the StO2 decreased to 40 %, at which time, the cuff was rapidly deflated (within 1 s) to 0 mmHg [3] (Fig. 2). A VOT was performed two times (at T1 and T2) by a single researcher (T.K.K.). First VOT was performed prior to the induction of anesthesia before applying oxygen (T1, Fig. 3). After administering induction drug, Tforearm-finger
was continuously monitored and calculated by a researcher (T.K.K.). T0 was defined as the start of anesthetic induction with midazolam, vecuronium, and sufentanil intravenous administration. The threshold for peripheral vasoconstriction was defined as T2, the inflection point at which a successive rapid increase in Tforearm-finger occurred [10]. At this T2 point, a second VOT was performed to quantify changes in microcirculatory vasoreactivity (Fig. 3). The second VOT was performed at 10.7 (4.8) min after T0. VOT was performed after a 3-min stabilization period. Stability was defined as StO2 variation \2 % over 30 s [3]. The StO2 values were recorded continuously on the monitoring device at 2-s intervals and were analyzed retrospectively using InSpectra Analysis software (InSpectra Analysis Program version 4.03; Hutchinson Technology Inc.). StO2 baseline average, VOT-derived occlusion phase parameters and recovery phase parameters were recorded. Peripheral perfusion was also evaluated by tissue hemoglobin index (THI) derived from the StO2 algorithm of the NIRS monitor. The amount of tissue hemoglobin present is influenced by blood hemoglobin concentration and microvasculature volume. THI provides a quantified value that corresponds to the amount of hemoglobin present within the volume of tissue [11]. 2.5 Cerebral oximetry Prior to induction of anesthesia, two cerebral oximetry (INVOS 5100Ò Cerebral Oximeter, Somanetics, Covidien) sensors were applied on the surface of the forehead on both the left and right sides after cleaning the skin with an alcohol swab. Regional cerebral oxygen saturation data were collected and continuously recorded at 30-s intervals using NIRS. Measurements began approximately 3 min after the sensors were applied. The averages of left and right values were used for data analysis. 2.6 Hemodynamic data
Fig. 2 Tissue oxygen saturation during a vascular occlusion test. StO2 tissue oxygen saturation
Cardiac output was measured noninvasively using a radial artery derived FloTrac sensor (Edwards Lifesciences, Irvine, CA, USA) connected to EV1000 monitor (EV1000TM; Edwards Lifesciences, Irvine, CA, USA) and corrected for body surface area to give the cardiac index. Cardiac index data were recorded at 20-s intervals. Blood pressure, heart rate and electrocardiography were monitored continuously during the study using the patient monitor (Solar 8000M, GE, Milwaukee, WI, USA). The pressure transducer was leveled to the mid-axillary line and the patient was in a neutral position lying flat on the bed during the study period.
123
J Clin Monit Comput
Fig. 3 Timeline for the study protocol. The second VOT was performed at 10.7 (4.8) min after start of anesthesia induction. VOT vascular occlusion test, T1 first VOT before applying oxygen,
T2 s VOT when forearm-minus-fingertip skin temperature gradients began to increase. T0 the start of anesthetic induction by the midazolam, vecuronium, and sufentanil intravenous administration
2.7 Statistical analysis
analyzed, at one or more timepoint, VOT data from 16 patients was not analysable because of an indistinct StO2 graph shape or data loss, the FloTrac-derived cardiac index from 14 patients was not analysable due to a data collection problem, and Tforearm-finger from two patients could not be analyzed due to data loss. None of the patients had more than two missing variables concurrently. Patient demographic data are shown in Table 1. During the study period, there was no episode of hypoxemia or hypercarbia monitored by pulse oximetry and ETCO2, respectively. Cerebral oximetry, ETCO2, cardiac index, heart rate, mean blood pressure, Tforearm-finger averaged over 1-min intervals are shown in Fig. 4a–f, respectively.
The primary end-point was VOT recovery slope at T2. One study reported that baseline recovery slope was 5.1 (3.89–5.53) % s-1 in patients undergoing major abdominal surgery [6]. We hypothesized that a 20 % increase in recovery slope at T2 was clinically relevant. A sample size of 32 patients was needed to detect a difference from baseline with a type I error of 0.05 and a power of 0.9. Considering possible dropouts, we chose to examine 50 patients. As our goal was to evaluate the effect of anesthesia induction on cerebral and tissue oxygenation, and since the maximum changes occurred within 20 min after anesthesia induction, consequently differences between maximal values within 20 min and at T0 for Tforearm-finger, cerebral oximetry, mean blood pressure, heart rate and cardiac index were assessed using a paired t test and Pearson’s correlations were used to test the relationship between them. Non-analysable data or data loss were excluded from correlation analyses. Mean values of StO2 and THI parameters derived from VOT at T1 and T2 were compared using a paired t test. Tforearmfinger, cerebral oximetry, mean blood pressure, heart rate and cardiac index were analyzed using repeated-measures analysis of variance at T0 and every minute for 60 min. All data were collected by dedicated researchers who were blinded to the specifics of the study. Results are expressed as the numbers of patients, the means (SD). p \ 0.05 was considered to indicate statistical significance. Statistical analyses were performed using SPSS 18.0 (SPSS Institute, Chicago, IL, USA).
3.2 Skin temperature Following administration of the intravenous induction drug, Tforearm-finger rapidly decreased from 1.9 (2.9) to -1.4 (2.2) °C (p \ 0.001). After 10.7 (4.8) min, Tforearm-finger decrease stopped and then began to rise. The pattern of Tforearm-finger during the interval following induction of general anesthesia is comparable with previous reports [12]. Table 1 Baseline characteristics Characteristic
Value
Number of patients
50
Age (year)
60.3 (15.0)
Sex (Male/female)
27 (54.0 %)/23 (46.0 %)
Weight (kg)
60.4 (11.7)
Height (cm)
162.0 (9.5)
3 Results
Body mass index
23.0 (3.8)
Diabetes
16 (32.0 %)
3.1 Patients’ characteristics
Hypertension
23 (46.0 %)
Hyperlipidemia
2 (4.0 %)
From July to October 2013, 113 patients were recruited for heart surgery registry. Among these 113 patients, two patients met the exclusion criteria for this subgroup study (patients being treated with vasoactive drug infusion). For this subgroup study, two specific measurements (continuous skin temperature monitoring at two sites and one more VOT during anesthesia induction) were needed, but, these were not available in 61 of the 113 patients due to equipment or personnel problems. Finally, 50 patients were enrolled and analyzed (Fig. 1). Among the 50 patients
123
Cerebrovascular disease
6 (12.0 %)
Beta blocker
13 (26.0 %)
Calcium channel blocker
9 (18.0 %)
Diuretics
16 (32.0 %)
Angiotension receptor blocker Angiotension-converting-enzyme inhibitor
8 (16 %) 3 (6 %)
Statin
11 (22.0 %)
Preoperative ejection fraction (%)
57.7 (11.7)
Data are expressed as a mean (SD) or number (%)
J Clin Monit Comput Fig. 4 Cerebral oximetry, end tidal carbon dioxide tension, cardiac index, forearm-minusfingertip temperature gradients, heart rate, and mean blood pressure averaged over 1-min intervals. Asterisks indicate significant change at individual time point compared with values at time 0 (repeatedmeasures analysis of variance, *p \ 0.05). T0: the start of anesthetic induction by the midazolam, vecuronium, and sufentanil intravenous administration. Values are shown as mean ± SE. ETCO2 end tidal carbon dioxide tension, Tforearm-finger forearmminus-fingertip temperature gradients
123
J Clin Monit Comput
3.3 Vascular occlusion test We performed VOT twice at T1 and T2. Dynamic parameters of the StO2 derived from VOT are presented in Table 2. VOT occlusion slope increased from -10.5 (4.5) % min-1 at T1 to -7.9 (2.8) % min-1 at T2 (p = 0.004). VOT recovery slope increased from 4.0 (1.5) % s-1 at T1 to 4.7 (1.3) % s-1 at T2 (p = 0.02). The dynamic parameters of THI did not reveal any significant change (Online Resource 1, which are dynamic parameters of THI and Online Resource 2, which are description of VOT parameters). The measurements of individual changes in VOT occlusion slope and recovery slope at T1 and T2 for each patient are presented in Fig. 5. A box plot of VOT occlusion slope and recovery slope are presented in Fig. 6. 3.4 Cerebral oximetry Following administration of the intravenous induction drug, cerebral oximetry began to rise rapidly, increasing from 64.0 (10.2) to 74.2 (9.2) % (p \ 0.001). After 7.1 (3.4) min, the increasing phase ended and cerebral oximetry decreased slowly and then stabilized at 59.2 (8.5) %. 3.5 Hemodynamic data Following administration of the intravenous induction drug, the cardiac index decreased gradually from 3.6 (1.8) to 2.2 (0.9) l min-1 m-2 (p \ 0.001). Heart rate also Table 2 Dynamic parameters of tissue oxygen saturation derived from vascular occlusion test
decreased from 74.8 (15.6) to 58.8 (12.8) (p \ 0.001). Mean blood pressure decreased from 90.2 (12.2) to 59.3 (11.3) mmHg (p \ 0.001). Mean blood pressure and cardiac index prior to time 0 are not shown in Fig. 4, because arterial line was generally established just prior to the start of anesthetic induction. Correlation analysis was performed between maximum changes of Tforearm-finger, cerebral oximetry, cardiac index, mean blood pressure, and VOT recovery slope within 20 min following induction of anesthesia. There was an inverse correlation between changes in Tforearm-finger and changes in cerebral oximetry (r = 0.33; p = 0.02) (Table 3).
4 Discussion The main finding of this study was that during anesthesia induction, blood pressure and Tforearm-finger decrease while cerebral oximetry and VOT recovery slope increase. The anesthetic-induced inhibition of thermoregulatory vasoconstriction is greatest when Tforearm-finger reaches the point of inflection [10, 13]. Therefore, increased VOT recovery slope at the Tforearm-finger inflection point reflects increased tissue microcirculation with peripheral vasodilation following anesthesia induction. Vasodilation does not always increase tissue perfusion. During septic shock, even with vasodilation, microcirculation is impaired [14]. In the study by Skarda [2], VOT recovery slope decreased in patients with severe sepsis. In T1 (n = 34)
T2 (n = 34)
82.6 (6.3)
83.5 (4.3)
-10.5 (4.5)
p value
Baseline parameter Baseline average (%)
0.40
Ischemia parameter Occlusion slope (% min-1)
-7.9 (2.8)
0.004
0.97 (0.38)
0.91 (0.19)
0.05
Occlusion slope tissue hemoglobin index adjusted
-137.0 (56.9)
-102.6 (41.5)
0.003
Ischemia area (% min)*
-107.1 (68.1)
-123.0 (77.6)
0.27
Occlusion slope fit (R2)
Recovery parameter Recovery slope (% sec-1) Recovery slope fit (R2)
4.0 (1.5)
4.7 (1.3)
0.02
0.98 (0.04)
0.99 (0.01)
0.10
Baseline recovery time (seconds after deflation)
19.2 (15.9)
14.1 (6.2)
0.09
Peak recovery time (seconds after deflation)
44.9 (48.0)
31.3 (12.3)
0.10
Hyperemia recovery time (seconds after deflation)
201.2 (118.6)
208.2 (108.6)
0.81
Baseline recovery area (% min)*
-5.6 (2.7)
-5.3 (2.3)
0.60
Hyperemia recovery area (% min)*
22.1 (21.2)
20.9 (12.1)
0.81
Data are expressed as a mean (SD) T1 first vascular occlusion test before applying oxygen, T2 s vascular occlusion test when forearm-minusfingertip skin temperature gradients began to increase * It is the integrated area of the graph for the time interval. Thus, it should be (% x min) or (%.min) for Ischemia area, Baseline recovery area, and Hyperemia recovery area (multiplication)
123
J Clin Monit Comput
Fig. 5 Individual changes in vascular occlusion test occlusion slope (a) and recovery slope (b) for every patient. VOT vascular occlusion test, T1 first VOT before applying oxygen, T2 s VOT when forearm-minus-fingertip skin temperature gradients began to increase
Fig. 6 Box plot of vascular occlusion test occlusion slope (a) and recovery slope (b). Occlusion slope increased from -10.5 (4.5) % min-1 at T1 to -7.9 (2.8) % min-1 at T2 (p = 0.004). Recovery slope increased from 4.0 (1.5) % s-1 at T1 to 4.7 (1.3) % s-1 at T2 (p = 0.02). Boxes represent the interquartile range
and the line inside represents the median. Whiskers represent 10/90 % quantiles and black dots represent outliers beyond the whiskers. VOT vascular occlusion test, T1 first VOT before applying oxygen, T2 s VOT when forearm-minus-fingertip skin temperature gradients began to increase
contrast, VOT recovery slope increased in the current study. VOT recovery slope is thought to reflect local tissue perfusion adequacy or local cardiovascular reserve because it represents the time required to wash out stagnant deoxygenated blood by oxygenated arterial blood during reperfusion [3, 4]. VOT recovery slope correlates with peripheral perfusion parameters but is independent of the systemic hemodynamic parameters in critically ill patients [15]. Since low StO2 and decreased VOT recovery slope have been associated with low peripheral flow index, indicating either vasoconstriction and/or impairment of microcirculatory flow [16], the increase in recovery slope and unchanged StO2 observed in this study following the
induction of anesthesia indicates local vasodilation and increased microcirculatory flow. In this study, VOT occlusion slope increased significantly following anesthesia induction, which suggests a decrease in the local metabolic rate since it is related to the rate of tissue oxygen consumption [3]. Thenar tissue metabolic rate may decrease because of the use of the neuromuscular blocking drug vecuronium during induction [17] or because of the preconditioning effect of VOT performed prior to anesthesia induction [18]. Cerebral oximetry measures the balance between cerebral oxygen supply and demand and correlates with changes in the cerebral blood flow when the arterial oxygen
123
J Clin Monit Comput Table 3 Correlation coefficients among the changes in forearm-minus-fingertip temperature gradients, cerebral oximetry, cardiac index, mean blood pressure, and vascular occlusion test recovery slope D Mean blood pressure (mmHg)
D VOT recovery slope (% s-1)
0.087
-0.102
0.075
0.62 35
0.50 47
0.68 33
D Cerebral oximetry (%)
D Cardiac index (l min-1 m-2)
1
0.327
48
0.02 48
D Tforearm-finger (°C) D Tforearm-finger (°C) r p n
D Cerebral oximetry (%) r
0.327
p
0.02
n
48
1
-0.022
-0.045
-0.319
0.90
0.76
0.06
50
36
48
35
1
D Cardiac index (l min-1 m-2) r
0.087
-0.022
p
0.62
0.90
n
35
36
0.141
-0.240
0.42
0.24
36
35
26
0.141
1
-0.226
D Mean blood pressure (mmHg) r
-0.102
-0.045
p
0.50
0.76
0.42
n
47
48
35
48
33
0.21
D VOT recovery slope (% s-1) r p
0.075 0.68
-0.319 0.06
-0.240 0.24
-0.226 0.21
1
n
33
35
26
33
35
Tforearm-finger forearm-minus-fingertip skin temperature gradients, VOT vascular occlusion test, D peak value after induction minus baseline value
saturation and cerebral oxygen consumption are constant [19]. Midazolam [20] and sufentanil [21] are known to reduce cerebral blood flow and cerebral metabolic rates by cerebral blood flow-metabolism coupling. An increase in cerebral oximetry despite decreased cerebral blood flow implies that metabolic rate decreased more than cerebral blood flow decreased [22], which may explain the mechanism by which cerebral oximetry values increased following the induction of anesthesia in this study. In the current study, the increase in cerebral oximetry was not maintained; rather it decreased and was stabilized within 15 min following a bolus administration of induction anesthetics (Fig. 4a). However, in the current study, BIS level decreased after administration of induction anesthetics and maintained a plateau throughout the induction period of over 30 min (Online Resource 3, typical pattern of BIS during induction of anesthesia) which was inconsistent with the pattern of cerebral oximetry (Fig. 4a). Since BIS correlates linearly with the magnitude of the cerebral metabolic reduction during anesthesia [23], decreased cerebral metabolic rate cannot solely explain the increase in cerebral oximetry. Another possibility is that cerebral oximetry could reflect increased cerebral microcirculatory flow following induction of anesthesia as identified in peripheral tissues using VOT in this study. Cerebral arteries are
123
abundantly innervated by sympathetic fibers [24], and induction anesthetics could induce a sympatholytic effect and cerebral arteriolar vasodilation. However, it is difficult to be concluded in the present study and further study is needed. In this study, despite significant decreases in the arterial perfusion pressure, oxygenation of both the brain and peripheral tissue as measured by cerebral oximetry and StO2 monitor increased during anesthesia induction. These findings suggest that anesthesia induction increased the tissue microcirculation. In this study, the lowest recorded mean arterial pressure was [65 mmHg; this might provide enough perfusion pressure to allow peripheral autoregulation. Note that this study was not planned to evaluate the clinical outcome. Additional studies are needed to evaluate the risk of anesthesia-induced hypotension. There were several limitations to this study. First, several factors which could affect cerebral oximetry could not be sufficiently controlled in this study. Cerebral oximetry values may be influenced by extracerebral tissue that can change the cerebral oxygen saturation by a variable amount [25], and StO2 has similar limitations [26]. It is thus possible that the increases in cerebral oximetry values that we observed were induced by alterations in extracerebral tissue oxygenation. Moreover, phenylephrine has been shown to reduce cerebral oximetry values in anesthetized patients
J Clin Monit Comput
[27]. In our study, phenylephrine was used in seven patients during anesthesia induction (20 min after T0) and this could have affected the cerebral oximetry values. Also, cerebral blood flow is sensitive to changes in PaCO2 and there was a period of hypoventilation during endotracheal intubation that may have increased PaCO2 concentrations. In the current study mean ETCO2 values were stable and did not exceed 40 mmHg at any time point. However, reliable ETCO2 monitoring was not available until after endotracheal intubation (Fig. 4b). Second, VOT has not been standardized with regard to the site of measurement, ischemic threshold, probe size and time interval between tests [28]. Moreover, during this study we found that the StO2 slope did not show clear linearity in 16 patients. These VOT data were not analyzed. Previous reports suggest that voluntary thenar muscle activity or technical aspects of the sampling can affect the potential for VOT non-linearity [3]. Third, there was missing data for FloTrac-derived cardiac index in 14 patients due to a data storage problem. Moreover, the reliability of the FloTrac sensor is still under debate [29]. Fourth, not only the brain but also the heart may be the organs most prone to ischemic injury during hypotension. While we did not specifically measure myocardial oxygenation in this study, we did not find any signs of myocardial ischemia on electrocardiography or transesophageal echocardiography. Fifth, we did not measure central temperature during the induction period. Finally, midazolam and sufentanil were used as induction anesthetics in the current study. Caution should be made in generalizing the outcomes to other induction anesthetics. In conclusion, during anesthesia induction, blood pressure and Tforearm-finger decrease while cerebral oximetry and VOT recovery slope increase. These findings suggest that anesthesia induction increases tissue microcirculation with peripheral vasodilation. Acknowledgments We thank to Medical Research Collaborating Center (MRCC) of Seoul National University Hospital (Seoul National University Hospital, Seoul, Korea) for the statistical assistance and supervision. None of the authors has a personal financial interest in this research. Conflict of interest Hippo Medical Company (Seoul, Korea) and Hutchinson (MN, USA) provided the InSpectraTM StO2 tissue oxygenation monitor during this study.
References 1. Alecu C, Cuignet-Royer E, Mertes PM, Salvi P, Vespignani H, Lambert M, Bouaziz H, Benetos A. Pre-existing arterial stiffness can predict hypotension during induction of anaesthesia in the elderly. Br J Anaesth. 2010;105(5):583–8. 2. Skarda DE, Mulier KE, Myers DE, Taylor JH, Beilman GJ. Dynamic near-infrared spectroscopy measurements in patients with severe sepsis. Shock. 2007;27(4):348–53.
3. Go´mez H, Torres A, Polanco P, Kim HK, Zenker S, Puyana JC, Pinsky MR. Use of non-invasive NIRS during a vascular occlusion test to assess dynamic tissue O2 saturation response. Intensive Care Med. 2008;34(9):1600–7. 4. De Blasi RA, Palmisani S, Alampi D, Mercieri M, Romano R, Collini S, Pinto G. Microvascular dysfunction and skeletal muscle oxygenation assessed by phase-modulation near-infrared spectroscopy in patients with septic shock. Intensive Care Med. 2005;31(12):1661–8. 5. Creteur J, Carollo T, Soldati G, Buchele G, De Backer D, Vincent J-L. The prognostic value of muscle StO2 in septic patients. Intensive Care Med. 2007;33(9):1549–56. 6. Futier E, Christophe S, Robin E, Petit A, Pereira B, Desbordes J, Bazin J-E, Vallet B. Use of near-infrared spectroscopy during a vascular occlusion test to assess the microcirculatory response during fluid challenge. Crit Care. 2011;15:R214. 7. Rubinstein EH, Sessler DI. Skin-surface temperature gradients correlate with fingertip blood flow in humans. Anesthesiology. 1990;73(3):541–5. 8. House JR, Tipton MJ. Using skin temperature gradients or skin heat flux measurements to determine thresholds of vasoconstriction and vasodilatation. Eur J Appl Physiol. 2002;88(1–2): 141–5. 9. Kurz A, Sessler DI, Christensen R, Dechert M. Heat balance and distribution during the core-temperature plateau in anesthetized humans. Anesthesiology. 1995;83(3):491–9. 10. Nakajima Y, Mizobe T, Matsukawa T, Sessler DI, Kitamura Y, Tanaka Y. Thermoregulatory response to intraoperative headdown tilt. Anesth Analg. 2002;94(1):221–6. 11. Myers D, McGraw M, George M, Mulier K, Beilman G. Tissue hemoglobin index: a non-invasive optical measure of total tissue hemoglobin. Crit Care. 2009;13(Suppl 5):S2. 12. Nakajima Y, Mizobe T, Takamata A, Tanaka Y. Baroreflex modulation of peripheral vasoconstriction during progressive hypothermia in anesthetized humans. Am J Physiol Regul Integr Comp Physiol. 2000;279(4):R1430–6. 13. Ikeda T, Sessler DI, Kikura M, Kazama T, Ikeda K, Sato S. Less core hypothermia when anesthesia is induced with inhaled sevoflurane than with intravenous propofol. Anesth Analg. 1999; 88(4):921–4. 14. De Backer D, Creteur J, Preiser J-C, Dubois M-J, Vincent J-L. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med. 2002;166(1):98–104. 15. Lima A, van Bommel J, Sikorska K, van Genderen M, Klijn E, Lesaffre E, Ince C, Bakker J. The relation of near-infrared spectroscopy with changes in peripheral circulation in critically ill patients. Crit Care Med. 2011;39(7):1649–54. 16. Lima A, Ince C, Bakker J. Use of tissue oxygenation saturation in association with skin temperature as an indicator of the peripheral tissue perfusion in critically ill patients. Crit Care. 2009;13:1–1. 17. Irish CL, Murkin JM, Cleland A, MacDonald JL, Mayer R. Neuromuscular blockade significantly decreases systemic oxygen consumption during hypothermic cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 1991;5(2):132–4. 18. Cortes D, Puflea F, Donadello K, de Backer D, Vincent J, Creteur J. Effects of rapid repetition of a vascular occlusion test on nearinfrared spectroscopy-derived variables in healthy subjects and in critically ill patients. Crit Care. 2013;17(Suppl 3):P2. 19. Wong FY, Nakamura M, Alexiou T, Brodecky V, Walker AM. Tissue oxygenation index measured using spatially resolved spectroscopy correlates with changes in cerebral blood flow in newborn lambs. Intensive Care Med. 2009;35(8):1464–70. 20. Baughman VL, Hoffman WE, Miletich DJ, Albrecht RF. Cerebral metabolic depression and brain protection produced by midazolam and etomidate in the rat. J Neurosurg Anesthesiol. 1989;1(1):22–8.
123
J Clin Monit Comput 21. Stephan H, Groger P, Weyland A, Hoeft A, Sonntag H. The effect of sufentanil on cerebral blood flow, cerebral metabolism and the CO2 reactivity of the cerebral vessels in man. Anaesthesist. 1991;40(3):153–60. 22. Lovell AT, Owen-Reece H, Elwell CE, Smith M, Goldstone JC. Continuous measurement of cerebral oxygenation by near infrared spectroscopy during induction of anesthesia. Anesth Analg. 1999;88(3):554–8. 23. Alkire MT. Quantitative EEG correlations with brain glucose metabolic rate during anesthesia in volunteers. Anesthesiology. 1998;89(2):323–33. 24. Busija D, Heistad D. Effects of activation of sympathetic nerves on cerebral blood flow during hypercapnia in cats and rabbits. J Physiol. 1984;347(1):35–45. 25. Sørensen H, Secher NH, Siebenmann C, Nielsen HB, Kohl-Bareis M, Lundby C, Rasmussen P. Cutaneous vasoconstriction affects near-infrared spectroscopy determined cerebral oxygen saturation
123
26.
27.
28.
29.
during administration of norepinephrine. Anesthesiology. 2012; 117(2):263–70. Creteur J, Neves AP, Vincent J-L. Near-infrared spectroscopy technique to evaluate the effects of red blood cell transfusion on tissue oxygenation. Crit Care. 2009;13(Suppl 5):S11. Meng L, Cannesson M, Alexander B, Yu Z, Kain Z, Cerussi A, Tromberg B, Mantulin W. Effect of phenylephrine and ephedrine bolus treatment on cerebral oxygenation in anaesthetized patients. Br J Anaesth. 2011;107(2):209–17. Go´mez H, Mesquida J, Simon P, Kim HK, Puyana JC, Ince C, Pinsky MR. Characterization of tissue oxygen saturation and the vascular occlusion test: influence of measurement sites, probe sizes and deflation thresholds. Crit Care. 2009;13(Suppl 5):S3. Monnet X, Anguel N, Jozwiak M, Richard C, Teboul J-L. Thirdgeneration FloTrac/Vigileo does not reliably track changes in cardiac output induced by norepinephrine in critically ill patients. Br J Anaesth. 2012;108(4):615–22.
