Lower BIS Values Research Articles

Cerebral Overperfusion Despite Reduced Cortical Metabolism Is Associated with Postoperative Delirium in Cardiac Surgery Patients: A Prospective Observational Study.

Background: Decreased cerebral oximetry (rSO2) in cardiac surgery is associated with postoperative delirium (POD). However, interventions optimizing intraoperative rSO2 are inconclusive. Methods: In this prospective observational cohort study, the relationship between rSO2, middle cerebral artery blood flow velocity (MCAV), and processed EEG was assessed in cardiac surgery patients with and without POD. MCAV was continuously recorded by transcranial Doppler sonography (TCD), together with continuous rSO2 and bispectral index (BIS) monitoring. Cardiopulmonary bypass (CPB) flow rate was adjusted according to body surface area. The cohort was divided into the POD and control groups, according to the postoperative results of the confusion assessment method (CAM/CAM-ICU), the 4A's test (4AT), and the Delirium Observation Scale (DOS). A mixed model analysis was performed for intraoperative raw data. The cerebral autoregulation index was calculated from TCD, rSO2, and arterial pressure values. Differences in impaired autoregulation were compared using the Mann-Whitney U test. Results: A total of 41 patients were included in this study. A total of 13 patients (36.11%) developed postoperative delirium. There were no significant differences in the baseline characteristics of patients with or without POD. Patients with POD had lower BIS values during CPB (adjusted mean difference -4.449 (95% CI [-7.978, -0.925])). RSO2 was not significantly reduced in POD, (adjusted mean difference: -5.320, 95% CI [-11.508, 0.874]). In contrast, MCAV was significantly increased in POD (10.655, 95% CI [0.491, 20.819]). The duration of cerebral autoregulation impairment did not differ significantly for TCD and cerebral oximetry-derived indices (p = 0.4528, p = 0.2715, respectively). Conclusions: Our results suggest that disturbed cerebral metabolism reflects a vulnerable brain which may be more susceptible to overperfusion during CPB, which can be seen in increased MCAV values. These phenomena occur irrespectively of cerebral autoregulation.

Incidence of dreaming during ciprofol anesthesia for painless gastroscopy.

Dreaming is often reported by patients who undergo propofol-based sedation, but there have not been any studies to date focused on the incidence of dreaming and factors associated therewith following the administration of ciprofol anesthesia in patients undergoing painless gastroscopy. The present study was thus developed with the goal of assessing the incidence of dreaming. In total, this study enrolled 200 patients undergoing painless gastroscopy. During the procedure, patients' electroencephalographic Bispectral Index (BIS), blood pressure (BP), heart rate (HR), blood oxygen saturation (SpO<inf>2</inf>), and PETCO<inf>2</inf> were monitored. When their MOAA/S score reached five after the procedure, patients were administered questionnaires including the Brice questionnaire and a five-point Likert Scale, and the content of any recalled dreams was also recorded. Overall, 27.5% of the participants in this study reported dreaming during the procedure, with most having experienced simple, pleasant dreams about everyday life. Identified predictors of dreaming during painless gastroscopy included lower ASA grade, preoperative knowledge of painless examination, a higher frequency of dreams in the month before the procedure, poor sleep quality during the month before the procedure, and shorter awakening time. Dreamers showed significantly lower BIS values at 2 min after endoscope insertion and following endoscope removal, and also showed lower minimum BIS values compared with non-dreamers. The postoperative dream recall incidence in this study was 27.5% among patients undergoing painless gastroscopy under ciprofol sedation anesthesia.

Intraoperative electrocardiogram monitoring induced bispectral index interference – A misleading heart–mind connection

Bi-spectral index (BIS) is a common but an important tool in anaesthesiologist's armamentarium across the world which helps to assess the level of sedation and effect of hypnotic drugs. A value between 40-60 in BIS is considered as optimal level of sedation during general anaesthesia. However, numerous factors can interfere with accurate BIS value. Electrocardiogram (ECG), has been mentioned as a factor resulting into fallacious BIS values in the literature, which may have significant implications on appropriate dosage of hypnotic drugs. ECG inferences are usually filtered by proprietary algorithm of BIS, and few cases have been documented wherein ECG interference resulted in fallacious BIS readings. Our case reports a less frequently reported interference in BIS values by ECG, which resulted into lower BIS values.

Evaluation of Prognosis of Coma Patients With Acute Brain Injury by Electroencephalogram Bispectral Index Monitoring.

The high mortality rate of comatose patients with traumatic brain injury is a prominent public health issue that negatively impacts patients and their families. Objective, reliable tools are needed to guide treatment decisions and prioritize resources. This study aimed to evaluate the prognostic value of the bispectral index (BIS) in comatose patients with severe brain injury. This was a retrospective cohort study of 84 patients with severe brain injury and Glasgow Coma Scale (GCS) scores of 8 and less treated from January 2015 to June 2017. Sedatives were withheld at least 24 hr before BIS scoring. The BIS value, GCS scores, and Full Outline of UnResponsiveness (FOUR) were monitored hourly for 48 hr. Based on the Glasgow Outcome Scale (GOS) score, the patients were divided into poor (GOS score: 1-2) and good prognosis groups (GOS score: 3-5). The correlation between BIS and prognosis was analyzed by logistic regression, and the receiver operating characteristic curves were plotted. The mean (SD) of the BIS value: 54.63 (11.76), p = .000; and GCS score: 5.76 (1.87), p = .000, were higher in the good prognosis group than in the poor prognosis group. Lower BIS values and GCS scores were correlated with poorer prognosis. Based on the area under the curve of receiver operating characteristic curves, the optimal diagnostic cutoff value of the BIS was 43.6, and the associated sensitivity and specificity were 85.4% and 74.4%, respectively. Taken together, our study indicates that BIS had good predictive value on prognosis. These findings suggested that BIS could be used to evaluate the severity and prognosis of severe brain injury.

The cumulative duration of bispectral index less than 40 concurrent with hypotension is associated with 90-day postoperative mortality: a retrospective study

BackgroundThe relationship between intraoperative low bispectral index (BIS) values and poor clinical outcomes has been controversial. Intraoperative hypotension is associated with postoperative complication. The purpose of this study was to investigate the influence of intraoperative low BIS values and hypotension on postoperative mortality in patients undergoing major abdominal surgery.MethodsThis retrospective study analyzed 1862 cases of general anesthesia. We collected the cumulative time of BIS values below 20 and 40 as well as electroencephalographic suppression and documented the incidences in which these states were maintained for at least 5 min. Durations of intraoperative mean arterial pressures (MAP) less than 50 mmHg were also recorded. Multivariable logistic regression was used to evaluate the association between suspected risk factors and postoperative mortality.ResultsNinety-day mortality and 180-day mortality were 1.5 and 3.2% respectively. The cumulative time in minutes for BIS values falling below 40 coupled with MAP falling below 50 mmHg was associated with 90-day mortality (odds ratio, 1.26; 95% confidence interval, 1.04–1.53; P = .019). We found no association between BIS related values and 180-day mortality.ConclusionsThe cumulative duration of BIS values less than 40 concurrent with MAP less than 50 mmHg was associated with 90-day postoperative mortality, not 180-day postoperative mortality.

Seen and Ignored: Are We Undermining Studies of Brain Health Interventions Before We Start?

Seen and Ignored: Are We Undermining Studies of Brain Health Interventions Before We Start?

Effect of intravenous lignocaine infusion on bispectral index during spinal anaesthesia for caesarean section: A prospective randomised double-blind study

Background and Aims:Systemic lignocaine has been shown to have sedative effects. We designed this randomised-double-blind, placebo-controlled study to evaluate the effect of intravenous lignocaine on the bispectral index (BIS) during caesarean section under spinal anaesthesia.Methods:80 patients scheduled for elective caesarean section under spinal anaesthesia were randomly allocated to 2 study groups. Group L received intravenous 1.5 mg/kg of lignocaine bolus, 15 minutes before spinal anaesthesia followed by an intravenous infusion 1.5 mg/kg/h for 60 minutes intravenously. The patients in the control group (C group) were given 0.9% sodium chloride in a double-blind fashion. Spinal anaesthesia was performed with 10 mg of 0.5% bupivacaine. The changes of Sao2, BIS and hemodynamic variables during caesarean section, Apgar score of neonate and the incidence of adverse effects were recorded.Results:BIS values were lower in the L group compared to C group (P ≤ 0.001). Comparison of mean arterial pressure (MAP) changes during spinal anaesthesia and surgery reveal statistically significant difference between two groups through repeated measure analysis (P ≤ 0.001), but comparision of heart rate (HR) changes during spinal anaesthesia and surgery failed to reveal any statistically significant difference between two groups. (P = 0.261). The Apgar scores did not reveal a significant difference between the two groups at first and five minutes after delivery (P = 0.99).Conclusion:Intravenous lignocaine infusion given with spinal anaesthesia in women undergoing elective caesarean delivery providing lower BIS values without respiratory depression, in the absence of foetal compromise.

The effects of dexmedetomidine on the bispectral index during cesarean section under general anesthesia with low-isoflurane anesthesia

Background Intraoperative awareness is a disturbing experience for all women undergoing general anesthesia for cesarean section; this may lead to posttraumatic stress which can last for many years. The bispectral index (BIS) is now widely used to evaluate the sedative hypnotic effect of anesthetic drugs. The effects of dexmedetomidine used with low concentration isoflurane on the BIS are investigated. Patients and methods After ethical approval, 40 parturients undergoing cesarean section received either normal saline, as a control group ( n =20), or 0.3 μg/kg/h intravenous dexmedetomidine 20 min before induction ( n =20) with anesthesia maintained using isoflurane 0.5 minimum alveolar concentration in 100% O 2 , fentanyl 1 μg/kg is given after fetal expulsion. Change in BIS, hemodynamic, uterine tone, Apgar score, sedative score, and pain score were recorded for all patients. Results Patients who received dexmedetomidine showed lower BIS values ( P P P P P P Conclusion The administration of dexmedetomidine 0.3 μg/kg/h is effective in maintaining a lower BIS with low-isoflurane anesthesia without adverse maternal or neonatal effects.

The effect of anesthesia depth on the oculocardiac reflex in strabismus surgery.

The aim of this study was to investigate the effect of the bispectral index (BIS) guided depth of anesthesia to inhibition of the oculocardiac reflex (OCR) during pediatric strabismus surgery. Patients between the ages of 3 and 16years who were scheduled for elective strabismus surgery were randomly assigned to two groups. In Group 1 (n: 32), the BIS values of the patients were maintained at <50; in Group 2 (n: 28), the BIS values of the patients were maintained at levels greater than or equal to 50 with 4-7% desflurane in a 50% O2-air mixture by titrating the concentration during the surgery. The heart rates, presence of dysrhythmia, anticholinergic drug usage and the type of the operated extra ocular muscle were recorded. The incidence of OCR was 25% in Groups 1 and 64.3% in Group 2, (p<0.05). Moreover, the incidence of OCR in group 2 was higher in medial rectus (MR) traction (78.9%) than in lateral rectus (LR) traction (33.3%) (p=0.035), with no significant difference in Group 1 between MR (21.1%) and LR (26.7%) tractions (p=0.83). We found that the lower BIS values are associated with the lower incidence of OCR in pediatric patients undergoing strabismus surgery. And our findings confirmed that the deeper anesthesia has a protective effect against the OCR.

Effect of magnesium sulphate on bi-spectral index (BIS) values during general anesthesia in children.

BackgroundMagnesium was reported to reduce both the anesthetic requirements and the period needed to reach a bi-spectral index value of 60 when used intra-operatively (Br J Anaesth 83:302-20, 1999; Anesth Analg 20:1273-5, 1988; Br J Anaesth 89:594-8, 2002; Anesth Analg 87:206-10, 1998; Br J Anaesth 89:594-8, 2002; Br J Anaesth 94:438-41, 2005) and to minimize the emergence agitation (Anaesthesia 61:1058-63, 2006). Previous studies examined the influence of magnesium on the anesthetic requirements while the bi-spectral Index values were kept within a constant range. We evaluated the effect of intraoperative magnesium on the bi-spectral index values during pediatric anesthesia while we kept other anesthetic variables unchanged.MethodsEighty pediatric patients with ASA physical status I, age 2–8 years and scheduled for minor infra-umbilical elective procedures included in a prospective randomized controlled study. We randomly divided patients into two groups. Group I (40 patients); received a bolus dose 50 mg/kg of magnesium sulphate followed by an infusion at rate of 15 mg/kg/h throughout the procedure. Group II (40 patients); received the same amount in the form of ringer acetate for blinding. We compared between the groups regarding: 1) BIS values. 2) Hemodynamic parameters. 3) Arterial oxygen saturation 4) End-tidal CO2 5) Respiratory rate and 6) Tidal volume.ResultsMagnesium group (Group I) showed significantly lower BIS values and shorter time to achieve BIS values below 60. Respiratory parameters (tidal volume and respiratory rate) were significantly lower in the magnesium group. Otherwise, no significant differences between the study group and the control group were detected.DiscussionOur study has the advantage of evaluating the direct effect of magnesium sulphate on the Bi-spectral index scale with keeping other intraoperative factors almost constant (as the type of operations, induction and maintenance techniques, end-tidal anesthetic concentration, analgesia and mode of ventilation) for accurate assessment.ConclusionMagnesium produced significantly lower BIS values, less time to reach BIS values below 60, lower tidal volume and lower respiratory rate during pediatric general anesthesia.Trial registrationPan African Clinical Trial Registry, www.pactr.org, PACTR201312000666231. Registered at 6 October 2013.

Management of general anesthesia in a child with Miller-Dieker syndrome: a case report.

Miller–Dieker syndrome (MDS) is a rare disorder characterized by type I lissencephaly and a distinctive facial appearance that may include prominent forehead, bitemporal hollowing, and micrognathia. MDS is associated with epilepsy. We here report an 18-month-old girl with MDS who required general anesthesia. The child had an extremely low Bispectral Index (BIS) value prior to undergoing general anesthesia. Her perioperative course was uneventful. This case highlights some of the important anesthetic concerns in patients with MDS, which include potentially difficult airways and extremely low BIS values.

Anesthetic depth and long-term survival: an update

The purpose of this paper is to review the current evidence relating anesthetic depth to long-term survival after surgery. Using PubMed as the principal source, this review included published studies in all languages comparing mortality in patients with low- and high-processed electro-encephalo-graphic index values. All published studies used the bispectral index (BIS) monitor to measure anesthetic depth. The majority of the published observational studies were post hoc analyses of studies undertaken for other purposes. Most of these studies report a statistically significant association between deep general anesthesia (i.e., BIS values < 45) and death. Some studies also suggest an association between deep general anesthesia and myocardial infarction or postoperative cognitive decline. The combination of low BIS values and low delivered anesthetic concentrations (thus defining increased anesthetic sensitivity) may identify patients at particularly high risk. One of the three available randomized controlled trials reports worse outcomes in the BIS = 50 group compared with the BIS > 80 group, and two report no difference in mortality between the BIS = 35 and BIS = 50-55 groups. The available evidence on anesthetic depth and long-term survival is inconclusive. Randomized controlled trials with carefully controlled arterial blood pressure are required.

Comparison of equi-minimum alveolar concentration of sevoflurane and isoflurane on bispectral index values during both wash in and wash out phases: A prospective randomised study.

Background and Aims:At equal minimum alveolar concentration (MAC), volatile agents may produce different bispectral index (BIS) values especially at low BIS levels when the effect is volatile agent specific. The present study was performed to compare the BIS values produced by sevoflurane and isoflurane at equal MAC and thereby assessing which is a better hypnotic agent.Methods:Sixty American Society of Anaesthesiologists I and II patients undergoing elective mastoidectomy were divided into groups receiving either isoflurane or sevoflurane, and at equi-MAC. BIS value was measured during both wash in and wash out phase, keeping other parameters same. Statistical analysis was performed using the Friedman two-way analysis and Mann-Whitney U-test. A P < 0.05 was considered significant.Results:BIS value was significantly lower with sevoflurane at all MAC values as compared to isoflurane, except in the beginning and at MAC awake. However, both the drugs proved to be cardiostable.Conclusion:At equi-MAC sevoflurane produces lower BIS values during wash in as well as wash out phase as compared to isoflurane, reflecting probably an agent specific effect and a deficiency in BIS algorithm for certain agents and their interplay.

Pretreatment with nitrous oxide enhances induction of anesthesia with sevoflurane: A randomized controlled trial.

Background and Aims:Inhalation anesthesia with sevoflurane may be enhanced by several drugs or techniques. The aim of the present study was to investigate the effect of nitrous oxide (N2O) pretreatment on the speed of anesthesia induction with sevoflurane.Material and Methods:Eighty patients scheduled for hysteroscopy under general anesthesia were randomly assigned to inhale for 10 min before induction 50% N2O in oxygen or air via a facemask. Anesthesia was induced with 7-8% sevoflurane in oxygen via a facemask. Bispectral index (BIS), end-tidal carbon dioxide (EtCO2) tidal volume, respiratory rate, oxygen saturation (SpO2), and heart rate were recorded every minute during the 10 min pretreatment periods and every 30 s during the first 300 s of induction with sevoflurane. During induction of anesthesia inspired and end-tidal sevoflurane concentrations were also recorded.Results:During the 10 min of inspired 50% N2O or air BIS, EtCO2, tidal volume, respiratory rate and heart rate values did not differ between the two groups except for the SpO2, which was higher in the N2O group (P < 0.001). During induction of anesthesia the N2O group exhibited lower BIS values (P = 0.001), being significant at 60-150 s (P < 0.001, P < 0.001, P = 0.002, P = 0.014) as well as at 270 s (P = 0.004). EtCO2 and tidal volume were consistently lower in the N2O group (P = 0.001, P = 0.041 respectively) and respiratory rate was higher (P = 0.007).Conclusion:Our results show that pretreatment of the patients with 50% N2O for 10 min enhances the speed of induction with sevoflurane as assessed by the BIS monitoring.

Propofol versus flunitrazepam for inducing and maintaining sleep in postoperative ICU patients

Context:Sleep deprivation is a common problem on intensive care units (ICUs) influencing not only cognition, but also cellular functions. An appropriate sleep-wake cycle should therefore be maintained to improve patients’ outcome. Multiple disruptive factors on ICUs necessitate the administration of sedating and sleep-promoting drugs for patients who are not analgo-sedated.Aims:The objective of the present study was to evaluate sleep quantity and sleep quality in ICU patients receiving either propofol or flunitrazepam.Settings and Design:Monocentric, randomized, double-blinded trial.Materials and Methods:A total of 66 ICU patients were enrolled in the study (flunitrazepam n = 32, propofol n = 34). Propofol was injected continuously (2 mg/kg/h), flunitrazepam as a bolus dose (0.015 mg/kg). Differences between groups were evaluated using a standardized sleep diary and the bispectral index (BIS).Statistical Analysis Used:Group comparisons were performed by Mann-Whitney U-Test. P < 0.05 was considered to be statistically significant.Results:Sleep quality and the frequency of awakenings were significantly better in the propofol group (Pg). In the same group lower BIS values were recorded (median BIS propofol 74.05, flunitrazepam 78.7 [P = 0.016]). BIS values had to be classified predominantly to slow-wave sleep under propofol and light sleep after administration of flunitrazepam. Sleep quality improved in the Pg with decreasing frequency of awakenings and in the flunitrazepam group with increasing sleep duration.Conclusions:Continuous low-dose injection of propofol for promoting and maintaining night sleep in ICU patients who are not analgo-sedated was superior to flunitrazepam regarding sleep quality and sleep structure.

Light levels of sedation and DSM-5 criteria for delirium

Dear Editor, In a recent opinion essay, Devlin and colleagues argue that sedation confounds reliable detection of delirium when using current assessment tools [1]. To support this, they state that a low Richmond Agitation and Sedation Score (RASS) or bispectral index (BIS) value increase the likelihood to screen delirium positive [2], and that sedation-induced delirium has a better prognosis than delirium that is unrelated to sedation. The issues raised by Devlin et al. are fundamental, as these refer to the question what delirium ‘really’ means. In the end, this question considers the definition that is used to diagnose delirium, also debated by Brummel and Ely [3]. Recently, the American Psychiatric Association adjusted the criteria for delirium in its fifth Diagnostic and Statistical Manual (DSM) of mental disorders (DSM-5) [4]. Compared to the fourth, revised edition (DSM-IV-R) [5], less emphasis has been put on a disturbance of consciousness, Table 1. Still, a patient at a light level of sedation may fulfil DSM-5 criteria for delirium. Low RASS and BIS values are not characteristic of sedation, and can also be observed in patients with hypoactive delirium who did not receive sedatives. Besides the unpublished study that is cited by the authors, other unpublished material suggests the opposite: the prognosis of sedation-induced delirium was found to be as bad as that of delirium due to other causes (T. Girard, personal communication, Annual Congress European Delirium Association, 20–21 September, 2013). Moreover, because of the complex, multifactorial nature of delirium, it may be questionable whether these two categories can really be distinguished. Delirium in critically ill patients usually results from a multitude of pathogenic factors including inflammation, multi-organ failure, metabolic disturbances, and medication effects. With current assessment tools light levels of sedation may be clinically indistinguishable from hypoactive delirium in which no sedation was used. There is a need for an objective delirium assessment tool that can also identify sedation effects. Electroencephalography with a limited number of electrodes and automatic processing is a promising

Bispectral index monitoring of sleep in palliative care patients

In patients receiving palliative care (PC), sleep is often negatively influenced by pain, anxiety and medication. Because these patients are often too sick to be investigated in a sleep laboratory, it is difficult to obtain objective information concerning their sleep. This study investigates whether bispectral index (BIS) monitoring reflects wakefulness, sleep and the effect of medication and whether it is tolerable for patients. In all, 10 patients from an inpatient PC unit participated in the study. They were monitored using a BIS system for one night, while each event was carefully documented by patient care attendants. In addition, participants completed a questionnaire on the evening prior to and on the morning following the recording about their subjective wellbeing and sleep. On a scale from 0 to 100, BIS measurements covered values ranging from a minimum of 29–40 to a maximum of 74–98. Individual differences between minimum and maximum ranged between 38 and 68. High BIS values are associated with wakefulness, low BIS values with sleep. The administration of sedative and analgesic medication was followed by a long-lasting decrease in BIS measurements. In 3 patients, the measurements were discontinued due to the patient being disturbed or irritation of the skin. BIS monitoring was well tolerated by most but not all patients. It can be useful in complementing patients’ reports in questionable cases. This might be of special interest in outpatient settings where continuous objective professional observation is not available.

Monitoring depth of anaesthesia in a randomized trial decreases the rate of postoperative delirium but not postoperative cognitive dysfunction

Postoperative delirium in elderly patients is a frequent complication and associated with poor outcome. The aim of this parallel group study was to determine whether monitoring depth of anaesthesia influences the incidence of postoperative delirium. Patients who were planned for surgery in general anaesthesia expected to last at least 60 min and who were older than 60 yr were included between March 2009 and May 2010. A total of 1277 patients of a consecutive sample were randomized (n=638 open, n=639 blinded) and the data of 1155 patients were analysed (n=575 open, n=580 blinded). In one group, the anaesthesiologists were allowed to use the bispectral index (BIS) data to guide anaesthesia, while in the other group, BIS monitoring was blinded. Cognitive function was evaluated at baseline, 1 week, and 3 months after operation. Delirium incidence was lower in patients guided with BIS. Postoperative delirium was detected in 95 patients (16.7%) in the intervention group compared with 124 patients (21.4%) in the control group (P=0.036). In a multivariate analysis, the percentage of episodes of deep anaesthesia (BIS values <20) were independently predictive for postoperative delirium (P=0.006; odds ratio 1.027). BIS monitoring did not alter the incidence of postoperative cognitive dysfunction (7th day P=0.062; 90th day P=0.372). Intraoperative neuromonitoring is associated with a lower incidence of delirium, possibly by reducing extreme low BIS values. Therefore, in high-risk surgical patients, this may give the anaesthesiologist a possibility to influence one precipitating factor in the complex genesis of delirium. Clinical trial registration ISRCTN Register: 36437985. http://www.controlled-trials.com/ISRCTN36437985/.

Concentration of Precious Sleep

Tailoring depth of anesthesia to the needs of each individual patient, while mastering the inevitable cardiovascular side effects represents a core anesthesiologist’s skill. Novel inspiration to this daily challenge has recently been brought by Sessler et al. ,1identifying the combination of low blood pressure, low bispectral index (BIS), and low minimum alveolar concentration of volatile anesthesia as a troika of death. Looking at the cutoff parameters of this “triple low” may cause a wave of reflection, if not immediate malaise in each anesthesiologist, as values below the mortality threshold are routinely tolerated. The question arises: Are we harming all these patients, if not worse?All three phenomena are inextricably entwined and intraoperative management is largely dictated by patient characteristics and intraoperative course. Low blood pressure was shown to determine adverse outcome in relation to age and duration of surgery,2and the establishment of a causal relationship between low BIS values and intermediate-term outcome previously failed when malignancy and physical status were considered.3Moreover, left ventricular dysfunction, systemic illness, or a complicated intraoperative course was shown to account for accumulated low BIS values, with no relation to end-tidal anesthetic gas concentrations.4The abovementioned results emphasize that anesthetic management is influenced not only by anesthesia-related, but also a plethora of surgery-related, and patient-specific factors. It seems difficult to control all these interfering factors to achieve clear-cut scientific conclusions; however, discrimination of at least American Society of Anesthesiologists physical status and cause of death seems mandatory. It is hard to believe that a triple low in a 20-yr-old American Society of Anesthesiologists class I patient has the same prognostic value, if any at all, as that of a 70-yr-old American Society of Anesthesiologists class III patient. Although Sessler et al . certainly would agree with these considerations, their current study misses the opportunity to provide conclusive new insights in conjunction with clinically applicable concepts as the predictive role of important variables such as comorbidities, American Society of Anesthesiologists physical status, duration and difficulty of surgery (e.g. , transfusion requirements), and cause of death were neglected. Moreover, no single low was associated with increased mortality, further impeding the identification of distinct manipulations of either mean arterial pressure, BIS, or minimum alveolar concentration as causal or pure epiphenomena. Hence, observation of a “double low,” and triple low should not be misinterpreted as differences in anesthetic sensitivity or outcome determinants per se . As before, attention is required not to injudiciously confound low BIS values as a pure reflection of anesthetic depth in the critically ill, just as the sufficient supply of minimum alveolar concentration values and provision of adequate perfusion pressures should be self-evident hallmarks of anesthesia.However, despite its limitations, the study shines with its conceptual approach of desperately needed outcome research in anesthesiology. Many aspects of narcosis remain unexplored and things working as a matter of course on a daily basis are likely to impact patient morbidity and mortality. Prospective studies regarding the prognostic value of anesthetic characteristics are desirable, in particular, those targeting outcome improvement. Data supporting clinical decision making will help to manage the core anesthesiologist’s task of tailoring anesthetic depth to each individual needs and answer the question: How can we make a difference for the better?

In Reply

We reported that a “triple low” of mean arterial pressure, minimum alveolar concentration (MAC), and Bispectral Index (BIS) is associated with a fourfold increase in 30-day all-cause mortality compared with patients without low values.1Yu and Liu point out that an association between triple lows and mortality may not be causal. We emphasized this obvious point in our article: “as in all registry analyses, it is impossible to make causal conclusions from these observations.”Nonetheless, our results indicate that two “double low” combinations and a triple low of mean arterial pressure, BIS, and MAC strongly predict postoperative mortality. We agree that triple low events are probably mostly markers for underlying disease. But perhaps some mortality can be prevented by anesthetic management—which remains an intriguing possibility.Yu and Liu also comment that we did not present baseline risk factors for various combinations of “single,” double, and triple low combinations. We instead used a sophisticated multivariable model to adjust for baseline factors. This is a more useful approach than stratifying by risk because, to the extent that relevant potential confounders were included, results in each patient group can thus be directly compared. The more important question is whether all relevant confounders were included. Surely some are missing because even a dense registry such as ours does not include every potential predictor. Importantly, though, we included Risk Stratification Indexes; these powerful predictors of mortality and hospital length-of-stay are based on 240 and 1,096 International Classification of Disease version 9 codes and thus subsume considerable patient-level baseline and procedural detail.2Yu and Liu state that we did not include intraoperative blood transfusion as a risk factor in our analysis. In fact, we did and our article specified that variables for each model were selected using forward conditional selection from a candidate pool containing “age, gender, race, body mass index, American Society of Anesthesiologists physical status, along with intraoperative factors including case-average estimates of blood concentration of propofol and fentanyl equivalents, estimated blood loss and administered erythrocyte volume, type of maintenance volatile anesthesia, whether nitrous oxide was used, and case duration.” Transfused blood volume remained in our final model for mortality and was reported in table 3.Postoperative troponin values are available only for a small fraction of nonrandom patients and thus could not be included. But even if they were available, troponin elevations are consequences of damage already done. And besides, postoperative laboratory values cannot be the basis for intraoperative management enhancements that might improve outcome—which is our real interest.We agree that only a clinical trial can determine whether intraoperative intervention to prevent or ameliorate triple low events actually improves outcomes. One (NCT00998894) is already in progress.Lotz and Kehl assert that we did not include cause of death, transfusion requirement, or American Society of Anesthesiologists physical status score in our analysis. As mentioned above, we did include transfusion requirement and American Society of Anesthesiologists physical status in the pool of candidate risk factors; details that were specified in the Methods section of our article. Physical status was retained in both the length-of-stay and mortality models as reported in tables 2 and 3. Lotz and Kehl also assert that we neglected case duration and complexity. As specified above, duration was directly included in our statistical model; and complexity is subsumed into the Risk Stratification Indexes. Cause of death is of interest, but date of death was obtained from the Social Security Death Index, which does not include mortality cause.Lotz and Kehl warn “not to injudiciously confound low BIS values as a pure reflection of anesthetic depth in the critically ill.” We fully agree and our article identified that there are “three potential causes of low BIS: (1) Low BIS is the normal response to generous doses of volatile anesthetics; (2) An alternative cause of low BIS is anesthetic sensitivity. This group is identified by the combination of low BIS and low MAC fraction. This is an atypical response because low MAC fraction should be associated with high BIS. That BIS was in fact low in some patients with low MAC fractions suggests an abnormal sensitivity to volatile anesthesia, potentially because of underlying illness; and (3) a third potential cause of low BIS is inadequate brain perfusion, resulting in ischemic suppression of brain metabolism. Brain hypoperfusion may especially occur in a fraction of patients who demonstrate low BIS combined with low mean arterial pressure.” This last group is potentially the most interesting because brain hypoperfusion should be preventable with adequate hemodynamic control.*Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio. ds@or.org