Entropy Monitoring Effect in Hepatic Cirrhotic Patients Undergoing Major Liver Resection on Sevoflurane Consumption and Hemodynamics

Journal of Anesthesia & Critical Care: Open Access

Entropy Monitoring Effect in Hepatic Cirrhotic Patients Undergoing Major Liver Resection on Sevoflurane Consumption and Hemodynamics. A Randomized Controlled Study

Abstract Research Article

Background and Goal of study: Inappropriate titration of the anesthetic agents Volume 5 Issue 3 - 2016 can lead to an under or excessive depth of anesthesia. Aim is to study effect of

patients with chronic hepatitis C (Child A) undergoing major liver resection on generalintroducing anesthetic Entropy requirements monitoring and during hemodynamics. major liver resection among cirrhotic 1Anaesthesia Departments of Liver Institute, Menoufiya Methods: 60 consecutive patients were randomly divided into two groups in a University, Egypt 2Faculty of Medicine, Menoufiya University, Egypt

Khaled Yassen, Anaesthesia butprospective obscured hospital from Anaethesist. based comparative Sevoflurane study with registered O2 /Air in50% Menoufiya at 2 l/min University, adjusted *Corresponding author: Egypt. Group I guided with Entropy, Group II also guided with standard practice Departments of Liver Institute, Menoufiya University, Egypt, to achieve a State (SE) and Response (RE) Entropy (40-60 with a gradient of 5-10. was more than 10 for more than two minutes. Sevoflurane (ml) consumed were Received:Email: June 01, 2016 | Published: July 28, 2016 Boluses of Fentanyl (1 - 2 µg/kg) were given if the difference between SE and RE

monitoredResults: Age, by GEweight Datex-Ohemda and fentanyl S/5 consumption Anesthetic Delivery were comparable Unit System. between both groups (P >0.05). Mean (SD) Sevoflourane consumption (ml) after 2hr, 4hr, and

6hr in GI (Entropy) versus II (Standard) were 16(2.19) vs 20.8(1.88), 10.7(1.94) vs 17.4(1.92), and 9(1.22) vs 14.1(2.19), P<0.01. Reduced end tidal sevoflourane (%) in G I (Entropy) vs GII after 2hr and 4hr (1.4 (0.12) vs 1.6 (0.07) and 1.4 (0.11) vs 1.6 (0.07). Total sevoflurane consumped was reduced by 31% in G I 0.05).(Entropy) An increasewhen compared in anesthesia with GIIdepth (Standard was observed Practice). in patientsThe Propofol not monitored induction dose with entropy was also lower (GI, 156.6+22.2 mg vs G II, 184.6+15 mg, P <

by Entropy in G II vs GI, repectively. SE after 2hr of anesthesia was 47 (4.44) vs 54 (6.58). RE after 2hr was 48(4.38) vs 53(6.96). Mean arterial pressure was reported to be higher in GI (Entropy) compared to GII during surgery. Extubation time and intensive care stay was shorter with Entropy (GI, 4.52±2 vs GII, 7.72±2 comparablemin, P <0.01) between and (1.40 both ± groups0.50 vs with 1.64 the ± 0.48, same days surgical P=0.09) and anrespectively. aesthetic team. Blood loss (ml) in GI 567.22±70.72 vs GII 571.2±72.28, P>0.05. Anaesthesia time was Conclusion agent consumption during induction and surgery and enhanced recovery with : Entropy monitoring for hepatic patients reduced general anaesthetic depth monitors can have an important economic impact when applied on a larger scale.favourable haemodynamic consequences. Encouraging the use of Anaesthesia

Keywords: Anaesthesia depth; Liver resection; Cirrhotics

Introduction may be unavoidable to achieve other critically important anesthetic goals [4]. Anaesthesia is a balance between the amount Liver cirrhosis is a progressive disease characterized by of the anesthetic drugs administered and the state of arousal of loss of functional hepatocytes with concomitant connective the patient which can vary throughout surgery with different tissue and nodule formation in the liver. The morphological and metabolic and hemodynamic circumstances. Inappropriate physiological changes associated with the disease substantially titration of the anesthetic agents can lead to an under or excessive affect drug pharmacokinetics [1]. Liver resection is the surgical depth of anesthesia (DOA) which might compromise patient removal of a part of the liver and it is a major lengthy operation outcome in particular those with co-existing medical disease [5,6]. with greater risk of hemodynamic instability during surgery [2,3]. The traditional signs for light anesthesia such as hypertension, In these patients, lower levels of anaesthetic are often used to tachycardia and lacrimation are unreliable indicators of the prevent adverse effects on the cardiovascular system and these anesthetic depth [7]. levels can be inadequate so; unintended intraoperative awareness

Submit Manuscript | http://medcraveonline.com J Anesth Crit Care Open Access 2016, 5(3): 00185 Entropy Monitoring Effect in Hepatic Cirrhotic Patients Undergoing Major Liver Copyright: Resection on Sevoflurane Consumption and Hemodynamics. A Randomized Controlled ©2016 Yassen et al. 2/8 Study

the depth of anesthesia and hypnosis level. Liver cirrhosis leads to resection (more than 3 segments) for hepatic tumors were Processed electroencephalogram (EEG) as Entropy can monitor includedclassification in this A prospective (Child A) with hospital cirrhosis based undergoing randomized major controlled liver a reduction in liver mass and hepatic blood flow with an effect on increasedrug clearance and decrease and cardiovascular in entropy scores stability. are related Entropy to monitoringthe level of study. In Group I the general anesthetic depth during induction allows for the quantification of cerebral neural activity. The anand anesthetic maintanence depth was using guided haemodynamics with the Entropy and clinicalmonitoring, signs while of an in Group II the depth was guided with standard practice of titrating consciousness under anesthesia. EEG entropy is a monitor based blinded) from the anesthetic team managing this group. on EEG analysis used in measuring hypnosis levels. EEG-entropy aesthetic depth, the Entropy monitor was kept away (Obscured, has two measurements: State entropy (SE) receives information Clinical laboratory and ultrasound evidence were used to from the brain waves and response entropy (RE) incorporates diagnose cirrhosis. They were divided into two equal groups by a information from the frontal electromyography. SE is computed simple random technique (closed envelopes). using EEG data from the previous 15 s, between 0.8 and 32 Hz, frontaland shows muscle, the value and shows in the therange value of 0–91. in the RE range is computed of 0–100 from [8-10]. 32 A and undergoing major liver surgery for more than 6 hours. to 47 Hz with 1.92 s, and reflects fast muscular activity from the Inclusion criteria include Age18-60 year, CHILD classification psychiatric disorders, chronic use of anticonvulsant or other Exclusion criteria include patients with known neurologic or fromAn facial EEG muscle signal measuredactivity [11]. with While frontal the lower electrodes frequencies includes (up a significant electromyographic (EMG) component originating cardiovascular, respiratory or renal diseases, patients with long- termcentrally drug active or alcohol medications, abuse, patients patients with with body clinically mass index significant > 40 decreases exponentially at higher frequencies. In contrast, the to about 32 Hz) contain predominantly EEG signals, EEG power (morbid obesity) and non-major hepatic surgical procedures. In the operating room, standard monitors were applied (Mean EMG has a wide noise like spectrum and dominates at frequencies higher than 32 Hz. While EMG activity normally is treated like an arterial blood pressure, ECG, Pulse oximeter, and Capnograph), entropyartefact, andthe theM-Entropy response module entropy claims [11]. to separate out both EEG and a left (Right handed patients) wrist or forearm vein was and EMG activity and generates two distinct numbers, the state and mean arterial blood pressure were obtained in the operating roomcannulated before for induction infusion of of anesthesia. intravenous After fluids. administration Baseline heart of 100% rate oxygen, anesthesia was induced with Propofol 2mg/kg IV, and RE becomes equal to SE when the EMG power is equal to zero, as the RE–SE-difference might then serve as an indicator for EMG to facilitate tracheal intubation. After tracheal intubation, the activation. SE should provide a measure of the current cortical patientFentanyl was 2µg/kg mechanically IV. Rocuronium ventilated 0.6 mg/kgwith a IVtidal was volume administered of 6-8 maystate ofincrease the patient. as a REresult by reflecting of intensive EMG nociceptiveactivity is thought stimulation to be ml/kg and peep adjusted to 5 mmHg, with the ventilatory rate andan indirect during measuredecreasing of adequacylevels of ofanesthesia. analgesia, Patients since EMG with activity liver maintaining an end-tidal carbon dioxide concentration (partial disease carry a risk of peri-operative morbidity and mortality related to the extent of their liver dysfunction [12,13]. In patients inspired concentration) in combination with air and oxygen (FiO2 with compromised liver function preservation of the remaining pressure) of 30–35 mmHg. Followed by Sevoflurane 2% (initial function is essential, otherwise, peri-operative complications are of general anesthesia. high. 50 %), the fresh gas flow rate was set to 2 L/min for maintenance Intermittent bolus doses of rocuronium (0.05 mg/kg IV) were Anesthesia and surgery can precipitate an overt hepatic administered according to the results of the train of four (TOF). dysfunction in patients suffering from liver disease and this varies from a patient to another according to the severity of the illness. The primary aim of this study is to investigate the intra- Subsequently, anesthesia was maintained with sevoflurane and operative effect of entropy monitoring on the general anesthetic anestheticsfentanyl. The were processed decided EEG by the parameters attending were anesthetist obscured based in theon requirements during major liver resection among cirrhotic standard practiceclinical signs group and (Group aiming II), to and provide dosage a rapid adjustments recovery. of patients with chronic hepatitis C (Child A). The appropriate anesthetic depth is maintained with entropy monitoring in one group and with the traditional monitoring method without Group I patients (CHILD A) guided with M-Entropy module theof theforehead S/5e was Anaesthesia cleansed, Monitoran entropy by sensor GE Healthcare was positioned Finland as and end tidal concentration will be observed and reported. The (former, Datex-Ohmeda, Helsinki, Finland) [9]. After the skin in secondaryentropy. The aim effect will be of whether Entropy adopting on consumption, entropy to economic guide general cost biosignal from the patient’s forehead was started while the patient anesthetic requirements will have an effect on the haemodynamic wasrecommended awake. The by impedance the manufacturer for the entropyin Group sensor 1. Recording was checked of the parameters during the surgery. from the fronto-temporal region of the patient’s head with a self- Patients and Methods and noted before induction. A 1-channel raw EEG is collected After local ethics committee approval of the National Liver adhesive Entropy Sensor (GE Healthcare, Finland) consisting of three electrodes. The signal is amplified, digitized, and processed Abdel Latif on 15th in the M-Entropy module. Sevoflurane end tidal concentration was informedInstitute, Menoufiyaconsents. 60 University, consecutive Egypt hepatic (Chairman patients Prof Child-Pugh Hossam a gradient of 5-10. Intermittent intravenous boluses of Fentanyl December 2010, RCT,16/2010) and written adjusted to achieve a State and Response Entropy of 40–60 with

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mg/kg IV and atropine 0.01 mg/kg IV. Measurements include more than 10 for more than two minutes. (1 - 2 µg/kg) were given if the difference between SE and RE was were recorded at 2 min intervals during the induction and every 2Entropy; hours during State Entropythe maintenance (SE), and period Response of the Entropy general (RE) anesthetic. values The SE (range from 0 to 91) and the RE (range from 0 to 100). Propofol and Fentanyl induction dosage and consumption RE becomes equal to the SE when there is no electromyographic every two hours. Mean blood pressure, central venous pressure activity. Recommended range for adequate anesthesia for both and the urine output will be recorded every 2 hours. The blood parameters is from 40 to 60, when SE increases above 60 the products required and any rescue drugs as ephedrine, atropine thisanesthetic is interpreted drug dosage as a sign was of increased. uncovered In nociception, contrast, if and SE more is in or adrenaline were recorded. After 24 hours follow-up, patients analgesicthe recommended medication range, (Fentanyl) but RE was increases required. 5–10 units above it, were asked if they can recall any events related to the operation. Operative time and Intensive care stay period is also reported. practice of titrating anesthetic depth. Standard practice includes Statistical Analysis theGroup clinical II techniques patients (CHILD used to A) assess guided intraoperative with standard consciousness traditional All data were tested with Kolmogorov- Smirnov Z test and pupillary responses or diameters, perspiration, and tearing. most of them were found normally distributed and so presented Conventionalas checking for monitoring movement, systems response include to commands, standard eyelash monitoring reflex, (Hemodynamic parameters and Capnography) as well as end- testes were used for associations or correlations as appropriate. with mean ± SD in tables. Both parametric and non-parametric II), if the patient displayed autonomic signs consistent with inadequatetidal anesthetic anesthesia analyzer. (e.g., During increased the maintenance heart rate, blood period pressure, (Group Expected frequency of liver resection cases in the year is 50 cases. or lacrimation) supplemental dose of fentanyl was administered. Percent of liver resection in cirrhotic cases is 20.0%. Confidence andinterval sample was size estimated equals 20. to beData 95.0% was statistically and power ofanalyzed the study using is 1% if the patient manifested a sustained (5 minutes) increase in SPSS80.0%. (statistical Relative riskpackage for liverfor social resection science) in cirrhotic program cases version is 0.213 theHowever, mean thearterial inspired blood sevoflurane pressure (MAP) percentage 20% of was the increased pre-incision by baseline value. Friedmanfor windows test and were for performed all the analysis to differentiate a (p<0.05) changes was consideredin different In response to clinical signs of excessive anesthetic effect statistically significant. Repeated measures ANOVA test and (e.g., a decrease in MAP 20% of the pre-incision value), the Resultsfollow up results. Spearman correlation coefficient. Sixty nine patients were included in the study, two were Transoesophagealinspired concentration Doppler of sevofluranemonitoring [14] was or decreased by a decrease by 1%. in Hypotension was treated with IV fluid replacement guided with allowed to proceed for right hepatotomy resection due to surgical extensionexcluded due of the to atumor faulty and Entropy were notelectrode, included while in the seven study, were two not of decreasedsevoflurane in concentration, case of bradycardia and finally, or IV by atropine ephedrine 0.5–1 3–6 mg IV if it was judged necessary. The Sevoflurane concentration was these three were treated with intraoperative radiofrequency and adrenaline were recorded. was administered. Rescue drugs such as ephedrine, atropine or concerningthe other five sex, with age aand limited body hepaticmass index segmentectomy. (BMI). 80% malesThe study and 20%demonstrated females were insignificance in each group. difference Table 1 presents between the both mean groups value surgicalSevoflurane team was (ml) the consumed same for all in boththe procedures; groups were an monitoredultrasonic dissectorby GE Datex-Ohemda was used to S/5divide Anesthetic the liver Delivery parenchyma. Unit System. No Pringle The maneuver was performed. The middle hepatic vein was preserved. (SD) of age 50.9 (11.23) years in GI, versus 50 (10.71) in G II and Measures to reduce intraoperative bleeding included: maintaining the mean (SD) body mass index (BMI) G I 27.6 (2.6) versus 26.9 (3.6) kg/m2 in G II respectively. Duration of surgery was 5.1(0.3) a low positive central venous pressure during the process Table 1: of resection, careful parenchymal transection with Cavitron in G I versus 4.9(0.4) hours in GII, P >0.05. Patients’ characteristics of the three studied groups. Group I, harmonic scalpel. Low-molecular-weight heparin (40 mg of cirrhotic patients guided with entropy; Group II, cirrhotic patients guided enoxaparin)Ultrasonic Surgical was given Aspirator subcutaneously (CUSA), bipolaronce daily elctrocautery for all patients and by standardVariable practice; Group III, Groupnon-cirrhotic Mean(patients SD) guided by entropy.P from the second postoperative day until hospital discharge but I > 0.05 was repeatedly revised with coagulation studies. Any blood Age (years) products given were reported. II 50.9(11.23)50(10.71) I 26.5(3.8) > 0.05 At the end of surgery, in both groups, anesthesia was guided BMI (kg/m2) to achieve rapid recovery, it was allowed to accept state entropy II 27.6(2.67) values >60 in the period 15 min before the end of surgery I when the inhaled anesthetics were discontinued, and residual Duration of surgery neuromuscular blockade was reversed with neostigmine 0.05 II 7.1±0.3 <0.05 7.5±0.4

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A. Parameters measured during induction

a. Propofol consumption during induction: On comparing was significant decrease in Group II 36 (3.32) more than doses of intravenous Propofol consumption for the 2 studied B. ParametersGroup I 42 measured (3.22) (Table during 7). maintenance a. Sevoflurane consumption: After two hours from induction groups during induction, there was a significant increase 3-5in Group demonstrates II 184.6 (15.06) in details mg comparedthe following to Group hemodynamic I Entropy in the studied groups. Group II consumed 20.8 (1.88) monitored patients 156.6 (22.25), (P <0.05) (Table 2). Table ml more than Group I patients monitored by Entropy 16 (2.19) ml. Sevoflurane consumption after four hours from b. resultsHemodynamic findings duringparameters induction and maintenance. induction still showed the least value in Group I 10.7 (1.94) induction time P >0.05. After: two No minutes significant from differences induction, ml, when compared to Group II 17.4 (1.92) ml. Six hours from between GI and GII in mean arterial pressure at the preinduction Group I continued to consume less Sevoflurane than Group II Entropy guided patients, 9 (1.22) ml versus differencethere was betweensignificant them decrease (P >0.05). in MAP in both groups G II b. End14.1 (2.19) tidal ml sevoflourane respectively (Table 8). 88 (2.85) mmHg and G I 94 (3.61), but with no significant : End tidal sevoflourane; Group I Entropy guided had the least value 1.4 (0.12) after two After four minutes from induction, there was significant hours from induction then Group II 1.6 (0.07). Four hours decrease in MAP for Group II patients 85 (2.59) mmHg in from induction Group I 1.4 (0.11) also showed the least comparison with Group I Entropy monitored patients 89 value when compared to Group II 1.6 (0.07) and also after (3.89), (P <0.05). After six minutes from induction, Group six hours from induction Group I 1.3 (0.17) showed the least 86II patients (3.85) mmHg.MAP 80 According (2.69)mmHg to heartwas still rate, significantly there was less no c. Fentanylvalue when during compared maintenance: to Group II 1.6 (0.05) (Table 9). when compared to Groups I entropy monitored patients change between the two studied groups in fentanyl consumption after two, four and six There hours was from no induction significant P follow up times of measurement at 2, 4 and 6 minutes after >0.05 (Table 10). inductionsignificant for change the two at studied preinduction groups P time >0.05. and during the d. Central venous pressure and urine output during c. Entropy during induction: maintenance: Central venous pressure and urine output; i. State entropy (SE): The baseline of the state entropy; groups after two, four and six hours from induction P >0.05. after two minutes of induction for the two studied groups. showed no significant change between the two studied showed no significant change at pre-induction time and 2 Packed Red blood cells units were required for 4 patients After four minutes of induction, there was significant in Group II versus 2 patients in Group I. Fresh frozen plasma decrease in patients not monitored by Entropy Group (4 units) were required in Group I for 3 patients versus 3 54 (6.58). 6 minutes after induction, there was still a Table 2: II, 47 (4.44) more than Group I monitored with Entropy, patients in Group II . 42 (3.31) (Table 6). standard Propofol practice. induction dose for the studied groups. Group I, cirrhotic significant decrease in Group II 36 (3.37) versus Group I patients guided with entropy; Group II, cirrhotic patients guided by ii. Response entropy (RE) Variable Group Mean (SD) P- Value induction time and two minutes from induction showed no : Response entropy at the pre- I 156.6(22.25) Propofol (mg) II 184.6(15.06) significant changes. Four minutes after induction, there was < 0.01 significant decrease in Group II 48 (4.38) when compared Table 3:with Group I 53 (6.96). Six minutes after induction, there and Fentanyl consumption. Parameters measured during induction and maintenance of general anesthesia, Sevoflurane consumption, and End tidal Sevoflurane Percentage Variable T1 T2 T3 T4 T5 P-value

MAP (mmHg)

GI 96.4 ± 3.3 94.3 ± 3.6 89.7 ± 3.8 86.7 ± 3.8 87.3 ± 3.2 <0.05 GII 94.5 ± 3.4 92.9 ± 3.2 89.2 ± 3.5 86.7 ± 3.8 89.2 ± 3.5

HR (beat/min)

GI 87 ± 12.3 89 ± 12.3 82 ± 9.7 77 ± 9.0 87 ± 11.3 <0.05 GII 92 ± 8.8 85 ± 8.9 80 ± 11.4 76 ± 10.8 89 ± 8.7

State entropy (SE)

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GI 90 ± 0.6 61 ± 4.2 54 ± 6.5 42 ± 3.3 63 ± 4.2 <0.05 GII 90 ± 0.9 63 ± 4.7 52 ± 5.3 41 ± 3.6 60 ± 3.6

Response entropy (RE)

GI 100 ± 0.0 64 ± 4.1 53 ± 6.9 42 ± 3.2 62 ± 5.6 <0.05 GII 99 ± 0.6 65 ± 4.9 53 ± 5.6 41 ± 3.6 61 ± 4.2 P minChanges and 15of meanmin after arterial induction pressure (T2, (MAP),T3 and heartT4) respectively, rate (HR), stateand at entropy end of surgery(SE) and (T5). response entropy (RE) in GI (Group I, cirrhotic patients) and GII (Group II, healthy liver). Values are expressed as mean ± SD, -value < 0.05 was considered statistically significant. Before the induction (T1), 5 min, 10 Table 4: Mean arterial pressure (MAP) differences during induction for Table 6:

II, cirrhotic patients guided by standard practice. patients guidedState Entropy by standard (SE) practice.differences during induction for the studied the studied groups. Group I, cirrhotic patients guided with entropy; Group groups, Group I, cirrhotic patients guided with entropy; Group II, cirrhotic Variable Group Mean ( SD) P- value Variable Group Mean ( SD) P- value

I I MAP 0 (mmHg) > 0.05 > 0.05 II 96.3 (3.21) II 90(0.63) SE 0 I 94.3 (2.96) I 61(4.26)90(0.82) MAP 2 (mmHg) > 0.05 94.3 (3.62) II 88 (2.83) II 60(4.54) < 0.01 SE 2 I MAP 4 (mmHg) I 54(6.58) II 94.388 (2.83) (3.62) < 0.01 II 47(4.44) I SE 4 < 0.01 MAP 6 (mmHg) I 42(3.31) II 85.2(2.60)89.7(3.81) < 0.01 II 36(3.37) Data are presented as mean (SD) at two, four and six minutes after SE 6 < 0.01 induction (MAP 2, 4, 6). P P P < 0.05 considered significant, < 0.01 is Table 5: Data are presentedP as mean (SD) before the induction (SE 0), two, four and considered highly significant. six minutes after induction (SE 2, 4, 6) respectively. < 0.05 considered Table 7: patients guidedHeart by rate standard (HR) differences practice. during induction for the studied significant and < 0.01 considered highly significant. groups, Group I, cirrhotic patients guided with entropy; Group II, cirrhotic cirrhotic patientsResponse guided Entropy by standard (RE) differences practice. during induction for the Variable Group Mean (SD) ANOVA P- value studied groups. Group I, cirrhotic patients guided with entropy; Group II, Variable Group Mean ( SD) P- value I 87(12.32) 1.45 > 0.05 I 100(0.00) II 86(10.10) > 0.05 HR 0 (beat/minute) II 100(0.00) I RE 0 0.77 > 0.05 I 64(4.18) II 89(12.30) > 0.05 HR 2 (beat/minute) II 64(4.12) RE 2 I 90(9.96) > 0.05 I II 82(9.72) HR 4 (beat/minute) 2.69 II 48(4.38)53(6.96) RE 4 < 0.05 I 87(4.79) I 42(3.22) 0.17 > 0.05 77(9.08) II 78(4.57) II 36(3.32) HR 6 (beat/minute) RE 6 < 0.01

P Data are presented as mean (SD). ANOVA test was used for comparing HR P Data are presentedP as mean (SD) before the induction (RE 0), two, four and between the three groups before the induction (HR 0), two, four and six six minutes after induction (RE 2, 4, 6) respectively. < 0.05 considered minutes after induction (HR 2, 4, 6) respectively. < 0.05 is considered significant, < 0.01 considered highly significant. significant.

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Table 8: anesthesia administration during hepatic resection surgery in cirrhotic patients. Many previous studies on healthy liver patients Sevoflourane used for general anesthesia maintenance. The practice.differences between the three studied groups, Group I, cirrhotic patients guided with entropy; Group II, cirrhotic patients guided by standard on the consumption of hypnotic drugs, but only few studies monitoredreported the the influence effect among of the the depth cirrhotic of anesthesia patients. monitoring Patients Variable Group Mean ( SD) P with liver disease pose major challenges in operating room and I intensive care units because stress of anesthesia and surgery can Sevo. 2 hr (ml) precipitate overt hepatic dysfunction. In this current study, the II 20.8(1.88)16(2.19) results clearly demonstrated that the propofol dosage used in < 0.01 I the level of consumption in the entropy guided group of cirrhotic Sevo. 4 hr (ml) liversinduction undergoing guided a by major entropy abdominal showed surgery a significant respectively reduction (group in II 10.7(1.94) < 0.01 I) when compared with a similar group of cirrhotic patients, I 17.4(1.92) but guided by standard clinical practice (group II). Vakkuri et al Sevo. 6 hr (ml) also demonstrated similar results when they used the spectral II 9(1.22) entropy monitoring. They found a reduction in the anaesthetic < 0.01 concentrations in association with faster emergence [15]. Data are presented as mean (SD) the two groups14.1(2.19) two, four and six hours after induction (Sevo. 2hr, 4hr, 6r) respectively. P Wang PC et al. [16] also proved that the use of spectral entropy P for monitoring the depth of anesthesia or level of hypnosis in < 0.05 considered Table 9: surgery or painful procedures can reduce the consumption significant, < 0.01 considered highly significant. of drugs and shorten the recovery time of total intravenous End tidal sevoflourane (ET) recorded during general anesthesia anesthesia such as propofol in cirrhotic patients. Aimé et al. bymaintenance standard practice. .The differences between the studied groups. Group I, [17] investigated BIS and spectral entropy monitoring during cirrhotic patients guided with entropy; Group II, cirrhotic patients guided Variable Group Mean ( SD) P practice for 140 adult patients, they demonstrated that BIS and I 1.4(0.12) sevoflurane– sufentanil anesthesia in comparison with standard

II 1.6(0.07) spectral entropy guidance for the titration of sevoflurane results ET-Sevo. 2hr < 0.01 in a reduction of 29% in sevoflurane consumption which is close I 1.4(0.11) to our current study the savings in sevoflurane (31%). The price II 1.6(0.07) canof 250 easily ml ofbe sevofluranecalculated knowing in Egypt the is currently price of 1000electrodes L.E. while and ET-Sevo. 4hr < 0.01 the entropy electrode price is 50 L.E. The cost-benefit balance I 1.3(0.17) sevoflurane, and the duration of the procedures(Table 3&4). II 1.6(0.05) study, their study concluded that the use of Bispectal Index (BIS) ET-Sevo. 6hr < 0.01 The savings were far less significant by Yli-Hankala et al. [18] Data are presented as mean (SD) for the two groups at two, four and monitoring refunded the cost of the electrode in anesthetics P P six hours after induction (ET sevo. 2hr, 4hr, 6hr) respectively. < 0.05 lasting longer than 282 min; their use of a fresh gas flow of 3 L/ Table 10: Fentanyl dose in microgram (µg) used during general anesthesia considered significant, < 0.01 considered highly significant. maintenance min could explain this discrepancy. Pavlin et al. [19] used a BIS monitoringmonitor to throughout titrate the dosean entire of sevoflurane operating room and foundwas associated that end for the two studied groups. Group I, cirrhotic patients guided withtidal a concentration reduction in mean (ET) end-tidal was reduced gas concentration by 13%. Instituting of a potent BIS with entropy;Variable Group II, cirrhoticGroup patients guidedMean by( SD) standard P-practice. value reduction in anesthetics use occurred if we assume equivalent I 140(50.7) Fentanyl 2 hr (µg) > 0.05 inhaled anesthetic (sevoflurane), suggesting that a similar II 120(56.0) total gas flows in the two groups. There was a significant inverse I 80(56.0) correlation between mean end-tidal sevoflurane concentrations Fentanyl 4 hr (µg) > 0.05 a study to evaluate the effect of entropy monitoring on end- II 100(0.0) and mean BIS values. Choi SR et al. [20] had also performed

I 60(54.7) foundtidal sevofluranethat the blood concentration pressure (BP) and values recovery were higher, characteristics end-tidal Fentanyl 6 hr (µg) > 0.05 in pediatric patients undergoing Sevoflurane anesthesia. They II 50(54.7)

Data are presented as mean (SD) for the two groups at two, four and Standardsevoflurane group. concentration In their study, during the maintenance difference in was an loweranesthetic and six hours after induction (fentanyl 2hr, 4hr, 6hr) respectively. P recovery was faster in the Entropy group compared with the

< 0.05 forconcentration anesthesiologist between to maintain Entropy general and controlanesthesia patients at a higher were considered significant. Discussion significant. Without Entropy monitoring, there was a tendency monitoring, there was a reverse trend to maintain their patients used in the current study to monitor the titration of general end-tidal sevoflurane concentration. However, with Entropy Preoperative recognition of compensated or Entropy was at smaller end-tidal sevoflurane concentrations. Similar to our

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10.15406/jaccoa.2016.05.00185 Yassen K, Abdullah M, Koptan H, Elshafie M, Yehyia M (2016) Entropy Monitoring Effect in Hepatic Cirrhotic Patients Undergoing Major Liver Resection on Sevoflurane Consumption and Hemodynamics. A Randomized Controlled Study. J Anesth Crit Care Open Access 5(3): 00185. DOI: Entropy Monitoring Effect in Hepatic Cirrhotic Patients Undergoing Major Liver Copyright: Resection on Sevoflurane Consumption and Hemodynamics. A Randomized Controlled ©2016 Yassen et al. 7/8 Study current study results which showed that the entropy guided standard clinical practice group (II). rangeet al. [16], of 45-55 performed among a healthy study to live assess liver factors donors, influencing chronic hepatitis the end- B groups (I) had lower end-tidal sevoflurane concentration than the patientstidal concentrations undergoing ofhepatectomy isoflurane withinhepatocellular a bispectral carcinoma, index (BIS) and Takamatsu et al. [21] also investigated the accuracy of response end-stage liver disease patients undergoing liver transplantation. entropy, state entropy and BIS as indicators of nociception during The study showed that end-stage liver disease patients required between response entropy and state entropy can indicate hepatocellular carcinoma with cirrhosis required intermediate sevoflurane anesthesia to determine whether the difference inadequate analgesia. They concluded that neither response the least end-tidal isoflurane concentration. Patients with determine the strength of noxious stimulation. Lacking of exact end-tidal isoflurane concentrations; healthy live liver donors entropy and state entropy nor BIS was sufficiently accurate to guidelines for the adjustments of fentanyl boluses in the entropy required the highest end-tidal isoflurane concentrations to provide sufficient an aesthetic depth. They concluded that liver shortcoming in their study protocol. In our study hemodynamic function was the only significant factor influencing the likelihood responsesgroup according guided to theRE infentanyl relation dosage to hemodynamic in the standard changes practice was a requirementsof lowering the are end-tidal different isoflurane for patients concentration with various by 4 liver hours status, after group (II), while in entropy groups (I) the use of the response– theyanesthesia recommended induction thatbecause , this end-tidal anaesthesia isoflurane depth concentration monitoring state entropy difference of more than 5-10 was used to titrate strategy may protect the patients from intraoperative recall analgesics during anesthesia. The fentanyl dosage did not differ overdose of anesthesia, respectively, their results in cirrhotic a different kind of information about intraoperative nociception patientsor anesthesia with chronic over-depth hepatitis as aare consequence in agreement of with insufficient our current or thansignificantly mere hemodynamic in either groups. changes, Whether still warrantsSE-RE difference further studiesreveals study results concerning the expected reduction in the inhalation agent consumption in cirrhotics undergoing surgery. (TableAnother 5&6). study by Paul F et al. [22], suggested that, the depth of anesthesia monitor should display a good correlation between anesthetics and monitoring using the bispectral index, to the measured value and the patient’s physiologic responses decreaseSchumann the anesthetic R et al. [25], requirements also studied and thefacilitate titration recovery of volatile from during the perioperative period, independent of the anesthetic anesthesia unrelated to liver transplantation. They conducted agent being administered. In individual patients, increase in a retrospective analysis in recipients with and without such monitoring. The BIS group received less inhalational anesthetic compared to the control group. Their opinion was that, unless this observationthe RE-SE differencewas studied was by seenA. Vakkuri already et al. some [15] minutes study and before was monitoring result was integrated into an intraoperative algorithm the approaching emergence could be anticipated from SE. This and an early extubation protocol for fast tracking enhanced controlled phenomena, such as the respiratory sinus arrhythmia recovery, this utilization does not appear to provide a clinical [attributed 23] suggesting to the that findings the anesthetic of early recovery drug effect of othermay cease brainstem- at the brainstem level earlier than in the cortex. Both indices based suggest that an enhanced recovery protocol utilizing anesthesia depthbenefit monitoring but instead facilities drives nowcost. availableWe agree in with many this theaters opinion should and be developed in future studies and applied clinically with cost Thismainly can on be EEG considered content, i.e. the SE result and BIS, of showeda residual a delay drug compared effect on effective economic basis. with RE in returning to baseline at return of consciousness. correctly to a simple request. The sedative effect does not cease Most of the above mentioned studies results coincides with theEEG, moment although that brain the patientfunction opens has recoveredhis eyes. One sufficiently of the limitations to react this current study The end-tidal concentration requirements of of this current study was not discussing the recovery time because inhalational anesthetics were lower for patients with impaired our main concern was to study the intraoperative consumption liver status. The use of entropy to monitor levels of end tidal of general anesthetics, among cirrhotic patients subjected to a inhalational anesthetics is preferable to avoid unnecessary high concentrations of general anesthetics for this group of cirrhotic intraoperative; two, four and six hours after the induction (Table patients and also to reduce cost during prolonged surgical 7-10).major surgery, so retrieval of measurements were at fixed times procedures. The introduction of Anesthesia depth monitoring into the Liver Institute anesthetic practice can help improve V Bonhomme et al. [24] found an excellent global correlation increasingly requiring surgical procedures with the improvement 10 units in awake patients and during induction of hypnosis. inmonitoring quality of of medical this group care of byhepatitis the new C patients introduced in Egypt, antiviral which drugs are between BIS and SE. BIS was higher than SE in the range of which treat the virus but leaves the cirrhosis as it is. in anaesthesied patients. In those conditions, clinicians may Agreement between BIS and SE was good in awake patients and Conclusion observed with BIS, with a negative difference of approximately 10expect units observing when the SE patient values is similar awake. to While those inthat other would conditions have been of recording, differences of more than 20 units could frequently be general anesthetic agent consumption during induction and observed. These discrepancies are partially explained by scale surgeryIn conclusion and enhanced Entropy recovery monitoring with for favourable hepatic patients haemodynamic reduced differences. They can also be related to site of recording, and monitors can have an important economic impact when applied onconsequences. a larger scale. Encouraging the use of Anaesthesia depth possibly to the effect of EMG activity on BIS calculation. Wang CH

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