One of the most common concerns expressed by patients who are about to undergo anesthesia is that they will remember intraoperative event, It is the unexpected and explicit recall by patients of events that occurred during anesthesia (Orser, B.A. et al., 2008). Awareness with recall after general anesthesia is an infrequent, but well described phenomenon that may result in posttraumatic stress disorder (Sebel, P. S. et al., 2004). The use of neuromuscular blocking agents is associated with a higher intraoperative awareness incidence, as well as with implicit memory (Nunes, R. R. et al., 2007). Most frequently they remember an auditory perception (voices 66%, noises 17%), the feeling of motor function lost (not being able to breath 48%, sensation of paralysis 17%), pain (38%), feelings of helplessness, anxiety, panic, impending death, or catastrophe (34%). Depending of what part of the operation they remember, the pain can come from intubation, incision or the following surgical procedure (Radovanovic, D. et al., 2011). Motor responses and sympathetic activation can indicate light levels of anesthesia. Increased respiratory effort, accessory muscle use, swallowing, grimacing, and extremity motion are signs of insufficient anesthesia. Use of neuromuscular blockade eliminates the information that motor signs can provide regarding anesthetic depth. Sympathetic effects of light anesthesia include hypertension, tachycardia, mydriasis, tearing, and sweating. Such findings are nonspecific; thus, their absence or presence may be unreliable indicators of awareness. Indeed, concomitant medications such as β blockers and sympathetic blockade may diminish changes in heart rate and blood pressure(Duke, J. C. et al.,)

,Therefore, a more direct and reliable method of measuring anesthetic drug effects on the brain is highly desirable and has been the object of research for many years. Electro- encephalography (EEG) is an obvious brain monitoring modality because it is non-invasive and continuous. Many anesthetic drugs produce characteristic effects on the EEG, and these have been extensively studied (Andrew, T. et al., 2006).

The concept of entropy, originally derived from thermodynamics, has been successfully applied to EEG analysis. Various entropy algorithms have been used in clinical studies, but until now a commercially available monitor exists only for spectral entropy (Bruhn, J. et al., 2000).

PATIENTS AND METHODS

a randomized comparable prospective clinical trial in Iraqi center for heart disease started from April 2017 to January 2018, 44 adult patients underwent elective open-heart surgery divided into two groups, group (R) 22 patients were receiving 0.3 mcg/kg/min Remifentanil infusion and Group (P)

22   patients   were   receiving   propofol   infusion 50mcg/kg/min both for maintenance of anesthesia after induction and both before starting heart lung machine (HLM) i.e., pre bypass period. Patients in both groups were receiving same induction agent and technique.

Regarding entropy monitoring data were collected for HR, MAP, EEG (State entropy) levels on three occasions first data were recorded immediately after induction, second data were recorded after one hour, third one immediately before (HLM) started (bypass time).

Inclusive Criteria

1. Patients underwent CABG with
2. Cardiopulmonary
3. Adult group was
4. Randomized sex
5. ASA III, IV.

Exclusive Criteria

1. Pediatric
2. Congenital heart
3. Patients on chronic anti-psychiatric
4. Patients with history of neurological deficit or head
5. Emergency
6. On vasoactive agents.
7. When above with some degree of heart block.

Statistical analysis was performed using SPSS windows version 23 software. Suitable tables and graphs were used to describe the data. Student’s t test was used for comparison between continuous variables. P value ˂ 0.05 was considered significant.

RESULTS

The distribution of study patients by age and weight is shown in table and figure (3.1). Study patient’s age was ranging from 36 to 81 years with a mean of 56.36 years and standard deviation (SD) of ± 12.08 years. The highest proportion of study patients was found in age group 50 – 64 (36.4%). Regarding weight, it was ranging from 60 to 125 kgs with a mean of 81.86kgs and standard deviation (SD) of ± 14.78kgs.

We noticed that the mean of EEG measure was higher in propofol group of patients than the mean of EEG measure in Remifentanil group of patients after induction, 1st hour pre by pass, and 2nd hour pre by pass.

There was a statistically significant difference (P=0.016) between mean of EEG measures of the two groups in the 2nd hour pre by pass, while the differences were not statistically significant after induction and 1st hour pre by pass. The highest mean of EEG measure in the two groups was after induction (66.72 in propofol group of patients and 59 in Remifentanil group of patients).

The mean of MAP in study patients' groups is shown in table (3.3). The mean of MAP was higher among Remifentanil group of patients than the mean of MAP in propofol group of patients after induction and 2nd hour pre by pass, while the means of MAP were the same in the two groups 1st hour pre by pass, but the differences in means of MAP in the two groups were statistically not significant (P ≥ 0.05). The highest mean of MAP in Remifentanil group of patients was after induction (89.75), while the highest mean of MAP in propofol group of patients was 1st hour pre by pass (84.81).

The mean of heart rate was higher in Remifentanil group of patients than in propofol group of patients after induction, 1st hour pre by pass, and 2nd hour pre by pass.

There was a statistically significant difference (P=0.046) between means of heart rate of the two groups in the 2nd hour pre by pass, while the differences were not statistically significant after induction and 1st hour pre by pass.

The highest mean of heart rate in the two groups was after induction (79 in propofol group of patients and 83 in Remifentanil group of patients).

DISCUSSION

Regarding awareness during open heart surgery Serfontein L found in his study the intraoperative awareness during cardiac surgery may be the result of fluctuations in hypnotic state, so that conclude the recognition of high-risk patients, the use of balanced anesthesia techniques and increased attentiveness on the part of the anesthetist will go a long way in preventing intraoperative awareness There is evidence that using processed EEG monitors reduces the incidence of awareness (Serfontein, L. et al., 2010).

Inour study we use state entropy and vital signs as indicators for awareness in two groups, group R (Remifentanil) and group P (Propofol), we found that there is significant reduction in EEG with R group & HR with P group after 2hrs of induction, were the EEG P value 0.016, HR 0.046. There are nonsignificant results immediate after induction and after one hour in all parameters in both P group and R group, and there is no significant difference in MAP throughout this period. GunterN. Schmidt, M.D; et al found SE entropy change superior to MAP and HR to distinguish between different steps of anesthesia with propofol and Remifentanil during five minutes, SE significance started at fourth minute while MAP and HR significance started from the second minutes (Schmidt, G. N. et al., 2004), As we found that Remifentanil significantly decrease the level of awareness which was measured by state entropy, Amorin P, et al. found in their study that increase Remifentanil dose decrease EEG(Coste,

1. et al., 2004), also Ferreira DA, Nunes CS, Antunes LM, et al. Show that Remifentanil boluses significantly reduces spectral and response entropy value especially in female (Eur, J. et al., 2016). While Munchaster AR, et al study shown that EEG decreased paradoxically in six pts. From

21 patients was studied when the Remifentanil concentration decrease(Muncaster, A. R. et al., 2003), Guignard, Bruno MD; et al in their study show the relationships between Remifentanil effect-site concentrations and Changes in EEG, MAP, and HR ,were negatively correlated with Remifentanil effect-site concentration (Guignard,

1. et al., 2000)Groesdonk HV, Pietzner J, Borger MA et al, when they studied The incidence of awareness during cardiac surgery ,they conclude that, with respect to intraoperative awareness, the use of ultra-short-acting opioid should be considered as a safe method of management of patients undergoing a wide variety of cardiac operations(Groesdonk, H. V. et al., 2010). Elliott, Peter MD: et al study investigates the effect of Remifentanil of various rates of administration on

H.R and MAP in patients with coronary artery disease The results show that Remifentanil should be given by slow infusion to such patients because of severe hemodynamic instability i.e. sever hypotension, bradycardia with a reduction in systemic vascular resistance after Remifentanil boluses administration (Elliott, P. et al., 2000). R.E. Anderson, J.G. Jakobsson found During propofol anaesthesia both entropy parameters decreased with increasing sedation,SE 34(17-70) Compared with nitrous oxide when the loss of consciousness with nitrous oxide is not associated with change in entropy indices SE 88 (85_91) (Anderson, J. G. et al., 2004), thepropofo decrease H.R according to our results that agree with Hamzeh Hosseinzadeh, et al in their study of Hemodynamic Changes following Anesthesia Induction and LMA Insertion in comparison between Propofol, Etomidate, and Propofol & Etomidate they reported propofol use could be associated with significant decreased blood pressure, bradycardia, and prolonged apnea(Hosseinzadeh, H. et al., 2013).

Yağan, Ö. et al., in their study to investigate the effect of propofol on hemodynamic response in comparison with etomidate and Etomidate- Propofol Combination in Anaesthesia Induction, they found a significant decrease in MAP values with propofol group (Yağan, Ö. et al., 2015). Also, Masoudifar M, Beheshtian E. Their study showed that propofol significantly decrease the systolic, diastolic blood pressure and MAP in comparison with etomidate, while there were no significant differences in terms of H.R in both group (Masoudifar, M. et al., 2013).

CONCLUSION

Regarding awareness measured by entropy, we found that Remifentanil group statically significantly in second hour better than propofol in decreasing the awareness in open heart surgery. Negatively affect HR more statically significant with the propofol group than with Remifentanil. Effect on MAP not statically significant in both groups.

RECOMMENDATION

We recommended Remifentanil for maintenance of anesthesia in open heart surgery to decrease the risk of awareness and to maintain hemodynamic stability.

1. Orser, A., Mazer, C.D. and Baker, A.J. "Awareness during anesthesia." Cmaj 178.2 (2008): 185-188.
2. Sebel, P. S., Bowdle, T. A., Ghoneim, M. M., Rampil, I. J., Padilla, R. E. & Gan, T. J, et al. "The incidence of awareness during anesthesia: a multicenter United States study." Anesthesiology, 3 (2004): 833-839.
3. Nunes, R. R., Cavalcante, S. L. & Lobo, R. F. "Memórias explícita e implícita em anestesias com bloqueio neuromuscular e " São Paulo Med J, 125 (2007): 1294.
4. Radovanovic, & Radovanovic, Z. "Awareness during general anaesthesia-- implications of explicit intraoperative recall." Eur Rev Med Pharmacol Sci, 15.9 (2011): 1085-1089.
5. Duke, C. & Keech, B. M. "Dukes Anesthesia Secrets." In Dukes Anesthesia Secrets, Chapter 26, 174 (Fifth Edition).
6. Andrew, T. "Depth of Anesthesia Monitoring." In Depth of Anesthesia Monitoring, 4 (2006): 793-822.
7. Bruhn, , Ropcke, H. & Hoeft, A. "Approximate entropy            as            an electroencephalographic measure of anesthetic drug effect during desflurane anesthesia." Anesthesiology, 92 (2000): 715-726.
8. Serfontein, "Awareness in cardiac anesthesia." Curr Opin Anaesthesiol, 23.1 (2010): 103-108.
9. Schmidt, N., Bischoff, P., Standl, T., Hellstern, A. & Teuber, O, et al. "Comparative Evaluation of the Datex-Ohmeda S/5 Entropy Module and the Bispectral Index® Monitor during Propofol–Remifentanil Anesthesia." Anesthesiology, 101.12(2004): 1283-1290.
10. Coste, , Guignard, B. & Chauvin, M. "Remifentanil dose-response effect on EEG parameters and heart rate variability." European Journal of Anaesthesiology (EJA), 21 (2004): 31.
11. Eur, J. & Ferreira, D. A, et al. "The effect of a remifentanil bolus on the bispectral index of the EEG (BIS) in anesthetized patients independently from intubation and surgical " Anaesthesiol (2006).
12. Muncaster, R., Sleigh, J. W. & Williams,
13. "Changes in Consciousness, Conceptual Memory, and Quantitative Electroencephalographical Measures During Recovery from Sevoflurane- and Remifentanil-Based Anesthesia." Anesthesia & Analgesia, 96.3 (2003): 720-725.
14. Guignard, , Menigaux, C., Dupont, X., Fletcher, D. & Chauvin, M. "The effect of remifentanil on the bispectral index change and hemodynamic responses after orotracheal intubation." Anesthesia & Analgesia, 90.1 (2000): 161-167.
15. Groesdonk, H. V., Pietzner, J., Borger, M. A., Fassl, J., Haentschel, D. & Paarmann, H, et al. "The incidence of intraoperative awareness in cardiac surgery fast-track " J Cardiothorac Vasc Anesth, 24.5 (2010): 785- 789.
16. Elliott, , O’hare, R., Bill, K. M., Phillips, A.
17. & Gibson, F. M. "Severe cardiovascular depression with remifentanil." Anesthesia & Analgesia, 91.1 (2000): 58-61.
18. Anderson, G. & Jakobsson. "Entropy of EEG during anaesthetic induction: a comparative study with propofol or nitrous oxide as sole agent." Anesthesiology, 92.2 (2004): 167-170.
19. Hosseinzadeh, H., Golzari, S. E., Torabi, E. & Dehdilani, "Hemodynamic changes following anesthesia induction and LMA insertion with propofol, etomidate, and propofol+ etomidate." Journal of cardiovascular and thoracic research, 5.3 (2013): 109.
20. Yağan, Ö., Taş, , Küçü, A., Hancı, V. & Yurtlu, B. S. "Hemodynamic Responses to Tracheal Intubation Using Propofol, Etomidate and Etomidate-Propofol Combination in Anaesthesia Induction." J Cardiovasc Thorac Res, 7.4 (2015): 134-140.
21. Masoudifar, M. & Beheshtian, E. "Comparison of cardiovascular response to laryngoscopy and tracheal intubation after induction of anesthesia by Propofol and Etomidate." J Res Med Sci, 10 (2013): 870-874.