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Is hyperlipidemia a potential protective factor against intraoperative awareness in cardiac surgery?
© Zheng et al. 2016
Received: 9 September 2015
Accepted: 5 April 2016
Published: 12 April 2016
Intraoperative awareness is a dreaded complication that leads to psychological sequelae such as posttraumatic stress disorder, especially in patients undergoing cardiac surgery. This study investigated the incidence of awareness among patients receiving cardiac surgery and sought to identify the risk factors contributing to intraoperative awareness.
Patients with informed consent undergoing cardiac surgery from June to September in 2012 were enrolled. At least one structured interview was performed postoperatively with the modified Brice Interview Questionnaire to identify intraoperative awareness as confirmed awareness, possible awareness, and no awareness. Confirmed awareness events reported by patients were classified into different categories with the Michigan Awareness Classification Instrument. The questionnaire results were combined with the patient medical records. A logistic regression model was used to analyze the risk factors that may have led to intraoperative awareness.
An estimated 2136 patients were included, and 1874 patients completed at least one interview. 83 patients (4.4 %) were identified as possible or confirmed awareness, among which 46 (2.5 %) reported confirmed awareness. Patients who experienced confirmed awareness were mostly of Class 1 and 2, 15 and 24 patients respectively, which represented isolated auditory and tactile perceptions. And 11 patients reported feelings of distress intraoperatively. Hyperlipidemia was associated with intraoperative awareness (OR = 0.499, 95 % CI = 0.252–0.989, p = 0.043) and using chi-square test, however, no significance was found with logistic regression.
Patients undergoing cardiac surgery are at high risk for intraoperative awareness. Distress is a common feeling in patients with intraoperative awareness. Hyperlipidemia is a potential protective factor for intraoperative awareness in cardiac surgery.
Incidence of intraoperative awareness in reported studies
Myles, et al. 
Akavipat, et al. 
Sebel, et al. 
Sandin, et al. 
Xu, et al. 
Goldmann, et al. 
Gordon, et al. 
Wang Yun, et al. 
Xu, et al. 
Qian Wang, et al. 
The study was approved by the Institutional Review Board of Fuwai Hospital in Beijing, China. Patients with Written informed consents receiving selective cardiac surgery under general anesthesia from June to September in 2012 were enrolled. Inclusion criteria were patients older than 18 years, with normal mental status, and able to provide informed consent. Patients were excluded if they did not meet the criteria or were not able to complete the follow-up questionnaires: (1) died intra- or postoperatively in the hospital; (2) could not be extubated early within 3–6 days; (3) could not communicate readily; (4) had abnormal mental status.
A sample of 1525 patients was estimated initially based on our prior study  that found a rate of intraoperative awareness of 3.0 %. We took a possible loss-to-follow-up rate of 30 % into consideration and set the final sample target at 2136 patients.
Conduct of the study
Individual practitioners, who were blinded to the study, made anesthetic algorithms, including anesthetic drugs and depth of anesthesia monitoring case-by-case. All patients were transferred to the Intensive Care Unit (ICU) for a period of postoperative sedation and ventilation, and then transferred to wards where the patients were awakened and extubated.
Each patient was interviewed by research staff with the modified Brice Interview . The research staff classified each patient report into confirmed awareness, possible awareness, and no awareness on the basis of published definitions . Events were classified according to the Michigan Awareness Classification Instrument . Patients who reported awareness received follow-up interviews to determine if the events confirmed awareness. The occurrence of awareness during the ICU stay would be excluded.
The patient medical records were retrieved and combined with postoperative questionnaire results. Descriptive statistics were used to describe the incidence of intraoperative awareness of cardiac surgery. Comparisons of continuous variables between the “Confirmed Awareness” and “No Awareness or Possible Awareness” groups were conducted with the independent sample t-test, and categorical variables between groups with Fisher’s exact test or chi-square test, with or without Yates’ continuity correction. P values of less than or equal to 0.05 were considered to indicate statistical significance. The statistical analyzes were performed with SPSS 21.0 (SPSS Inc., Chicago, IL).
Occurrence of intraoperative awareness
Descriptions of confirmed awareness reported by patients
Gender and age
Michigan awareness classification
Formication; perception of central line placement; mild pain
Precordial stabs; nausea
Operation on the chest
Repair of aneurysm of aortic sinus, repair of VSD
Perception of central line placement
Placement of nasal thermometer
Modified Morrow procedure
A surgeon making explanations in a Tangshan accent
Wheat procedure and CABG
Dreaming things back in decades ago; lower extremity operation
Repair of aneurysm of aortic sinus
Intubation; operation, electroshock on heart
Intubation, feeling nausea twice
Scalpel incision; voice from doctors
Intubation; internal jugular vein catheterization
Sensation of operation on chest and lower limb
Resection of atrial myxoma, TVP
Feelings of bugs-like crawling on the chest
ASD repair, TVP
Sensation of sounds from the respirator
Heard the surgeons’ talking
Heard the sounds of electric scalpel, like “chi, chi”
Intubation; nausea; discomfort on the back
Water dripping-like sounds of the machine; sensation of intubation and a severe feeling of nausea
Sensation of the operation; severe pain, being unable to move
Correction of aberrant of pulmonary artery, TVP
Sounds of the machine in the operation room
Replacement of aortic root and ascending aorta
Sounds of a scalpel and scissor
Replacement of ascending aorta
Heard the surgeon talking about the electric defibrillations, of which only the third time worked
MVR, AVR, TVP
Heard the surgeon said the operation was well finished; intubation; felt nausea twice
Dreaming, cannot afford details; heard the surgeon’s talking; central line placement
Lower limb operation
Intubation; felt nausea; sensation of the operation on the chest
Operation on chest with burning heat
Repair of ASD, TVP
Sounds like sawing wood
Repair of ASD, TVP
Voice, such as “pass the scalpel to me”
Modified Morrow procedure
Operation on chest; severe pain, wanting for more anesthetics
Felt awake for a long time and felt like breathing with effort
Heard “chi-chi” like sounds
MVR, AVR, TVP
Heard the surgeon said the operation will be finished in an hour; heard the “dong-dong” like sounds
Dreaming of receiving cardiac surgery; sensed the central line placement
MVR, TVP, and PDA repair
Scissors cutting on the chest; mild pain
Operation on chest and lower limb
Something dragged down from the chest; unable to move; central line placement
Dreaming of the lifetime in high school; heard the surgeon said the operation was almost finished
Heard the surgeon said 5 bypass grafts were done, and the 2 nurses had done a great job
Intubation; unable to move; afraid
Chest stuffy, unable to speak
Replacement of descending aorta
Heard the surgeon said the operation was well done; felt his chest stabbed 4–5 times.
Risk factors for intraoperative awareness
Demographic characteristics of study population (n = 1874)
No awareness or possible awareness
< 60 year old
> 60 year old
165.7 ± 8.7
166.1 ± 8.1
68.0 ± 12.4
67.7 ± 12.9
24.8 ± 6.5
24.4 ± 3.7
Blood group-no. (%)
Existing risk factors-no. (%)
Chronic kidney disease
Chronic liver disease
Chronic obstructive pulmonary disease
History of general anesthesia
History of cardiac infarction
ASA status-no. / total no. (%)
Lower than Grade 1
Ejection fraction (%)
61.2 ± 8.7
62.3 ± 7.6
Duration of surgery-min
225.2 ± 82.4
195.0 ± 52.0
Cardiopulmonary Bypass-no. (%)
Duration of CPB-min
106.2 ± 47.4
91.2 ± 40.0
Aortic clamping time-min
71.7 ± 32.1
62.6 ± 33.3
Logistic regression analysis of risk factors for confirmed awareness
95 % CI for OR
Duration of Operation
In the present study, we found the awareness rate in cardiac surgery was 2.5 %, which was considerably higher than that in general surgery [2, 9–12]. Several factors may have contributed to the higher occurrence of anesthesia awareness. Patients are particularly vulnerable to awareness during painful procedures such as sternotomy, electrocauterization, or any surgical manipulations and strong stimulations like endotracheal intubation . Publications what address risk factors for more frequent awareness in cardiac procedures also mention compromised hemodynamics, insufficient anesthesia or analgesia that may have resulted from underdosing of anesthetic agents related to a patient’s specific requirements , and alterations in pharmacokinetics or pharmacodynamics of drugs during cardiopulmonary bypass .
The awareness rate in this investigation differed notably from other studies in cardiac surgery [2–4, 15–17]. The differences might be explained by methodology , human factors , and race; other factors that may have influenced the assessed awareness rate were the definition of awareness. Study methodology, including the number of patient interviews and especially the time elapsed after surgery when the patients were interviewed, and characteristics of the patients, as well as the number of patients evaluated. Another factor that likely influences inter-study comparability are the differences in routine practice between hospitals and between anesthesiologists, which is difficult to control in an analysis. Also, the ethnic difference may partially lead to the different results. Non-Chinese patients were enrolled in most of the prior studies, whereas all the patients in the present study were Ethnic Chinese. An ethnic difference has been reported in certain fields, like blood coagulation function and the fibrinolysis system [19, 20], along with differences in responses to special drugs, such as warfarin [21, 22].
Distribution of the timing of intraoperative awareness
In this study, 16 patients reported events that occurred after anesthesia induction, but prior to the skin incision, of which mostly are endotracheal intubation and central line placement. Although analgesics like fentanyl will blunt hemodynamic responses to intubation to some degree, attempting to attenuate arousal of cerebral cortical activity has failed . When a difficult airway is presented, multiple strong stimulations of intubation attempting might contribute to more frequent occurrences of explicit recall. Meanwhile, the depth of anesthesia will lower down once the maintenance of anesthesia is not scheduled during the attempting. During operation 18 patients experienced awareness, not being able to recognize the exact timing of the events. Only few events were well identified by specific time or manipulations, especially auditory perceptions and general manipulations that might occur throughout surgery. Five complaints occurred at the end of the surgery, which was when the depth of anesthesia was lowest to adapt to the reduced stimuli and avoid further compromising hemodynamics.
Michigan Awareness Classification
Confirmed awareness graded by the Michigan Awareness Classification is shown in Fig. 3. While the majority of awareness events in Classes 1 and 2 were related to auditory and tactile perceptions (39 of the 46 confirmed awareness events), only seven cases with mild-to-severe pain, with or without a sensation of paralysis, were classified as Grade 3 to 5. Meanwhile, 11 patients (24 %) experienced distress from fear, nausea and being unable to speak. In a previous prospective randomized trial, five out of nine patients had confirmed awareness of Class 1 and 2, and five out of nine cases experienced distress . These finding demonstrated that patients were more likely to experience a lower class of intraoperative awareness. However, distress during the period of awareness was frequently found. Therefore, careful postoperative follow-up should be arranged for patients complaining of awareness.
Hyperlipidemia and awareness
As shown in Table 3, patients who reported confirmed awareness had a shorter duration of surgery (195.0 ± 52.0 min vs. 225.2 ± 82.4 min, p = 0.013, OR = 0.994, 95 % CI = 0.990–0999), compared with the other patients. However, as the odds ratio is proximal to the value 1, duration of operation won’t be considered as a significant index for establishing a risk factor for the patients’ intraoperative awareness.
Interestingly, this study indicated that hyperlipidemia was negatively related to anesthesia awareness using chi-square tests, demonstrating that hyperlipidemia is a potential protective factor against intraoperative awareness in cardiac surgery. As the elder people suffer hyperlipidemia more frequently, to clarify that hyperlipidemia is an independent protective factor rather than a coincidence with old age, a logistic regression where age, duration of operation and hyperlipidemia were entered into was done and found no association between hyperlipidemia and awareness.
However, an animal experiment conducted in mice revealed that high cholesterol level increases the anti-nociceptive effect of opioids and an analysis of the clinical records in the China-Japan Friendship Hospital (Beijing, China) was carried out to conclude that there exists a reverse correlation between the serum cholesterol and opioid efficacy in human . As patients are subjected to awareness more often during painful procedures such as sternotomy and strong stimulations such as endotracheal intubation , the enhanced analgesia effect of opioids in the patients with hyperlipidemia like hypercholesterolemia will lower down the occurrence of anesthesia awareness. Nevertheless, a prospective cohort study is needed to reveal the relationship between hyperlipidemia and awareness. The coming era of translational medicine promises to clarify whether genetic variations contribute to a possibly lower risk of intraoperative awareness among patients with hyperlipidemia.
One of the limitations would be the timing for interviews. Since it is difficult to determine when patients will regain consciousness and as a result of the disability to communicate while still remain intubated for compromised hemodynamics, it is tough for the researchers to initiate the first interview at the appropriate time. Similarly, the patients would be discharged after surgery in 1 to 2 weeks, making it relative limited time for research staff to conduct the follow-up questionnaires. Since patients mostly report intraoperative awareness within 30 days, the true incidence of awareness may have been higher.
Another consideration is that the lack of appropriate hallmarks for identifying the specific timing of each reported events had complicated the analysis of the risk factors.
Patients undergoing cardiac surgery are at relatively higher risk for intraoperative awareness. Distress during awareness as an outstanding discomfort during the surgery with implications for postoperative psychological complications in the hospital and long-term outcomes following the awareness, deserves the attention of anesthesiologists. Hyperlipidemia is a potential protective factor for intraoperative awareness for patients receiving cardiac surgery.
We would like to express our great appreciation to Pro. Hushan Ao and Pro. Zhifa Wang for their valuable and constructive suggestions during the planning and development of this research work. And our grateful thanks are also extended to the staffs of the Department of the SICU, for their support of our work. We also would like to express special thanks to Dr. Lei Li, and Mr. Sipeng Chen for their critical suggestions on data collection and data analysis.
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