Anthony G. Messina

Background General anaesthesia is usually associated with unconsciousness. 'Awareness' is when patients have postoperative recall of events or experiences during surgery. 'Wakefulness' is when patients become conscious during surgery, but have no postoperative recollection of the period of consciousness. Objectives To evaluate the efficacy of two types of anaesthetic interventions in reducing clinically significant awareness: ‐ anaesthetic drug regimens; and ‐ intraoperative anaesthetic depth monitors. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, ISSUE 4 2016); PubMed from 1950 to April 2016; MEDLINE from 1950 to April 2016; and Embase from 1980 to April 2016. We contacted experts to identify additional studies. We performed a handsearch of the citations in the review. We did not search trial registries. Selection criteria We included randomized controlled trials (RCTs) of either anaesthetic regimens or anaesthetic depth monitors. We excluded volunteer studies, studies of patients prior to skin incision, intensive care unit studies, and studies that only randomized different word presentations for memory tests (not anaesthetic interventions). Anaesthetic drug regimens included studies of induction or maintenance, or both. Anaesthetic depth monitors included the Bispectral Index monitor, M‐Entropy, Narcotrend monitor, cerebral function monitor, cerebral state monitor, patient state index, and lower oesophageal contractility monitor. The use of anaesthetic depth monitors allows the titration of anaesthetic drugs to maintain unconsciousness. Data collection and analysis At least two authors independently scanned abstracts, extracted data from the studies, and evaluated studies for risk of bias. We made attempts to contact all authors for additional clarification. We performed meta‐analysis statistics in packages of the R language. Main results We included 160 studies with 54,109 enrolled participants; 53,713 participants started the studies and 50,034 completed the studies or data analysis (or both). We could not use 115 RCTs in meta‐analytic comparisons because they had zero awareness events. We did not merge 27 of the remaining 45 studies because they had excessive clinical and methodological heterogeneity. We pooled the remaining 18 eligible RCTs in meta‐analysis. There are 10 studies awaiting classification which we will process when we update the review. The meta‐analyses included 18 trials with 36,034 participants. In the analysis of anaesthetic depth monitoring (either Bispectral Index or M‐entropy) versus standard clinical and electronic monitoring, there were nine trials with 34,744 participants. The overall event rate was 0.5%. The effect favoured neither anaesthetic depth monitoring nor standard clinical and electronic monitoring, with little precision in the odds ratio (OR) estimate (OR 0.98, 95% confidence interval (CI) 0.59 to 1.62). In a five‐study subset of Bispectral Index monitoring versus standard clinical and electronic monitoring, with 34,181 participants, 503 participants gave awareness reports to a blinded, expert panel who adjudicated or judged the outcome for each patient after reviewing the questionnaires: no awareness, possible awareness, or definite awareness. Experts judged 351 patient awareness reports to have no awareness, 87 to have possible awareness, and 65 to have definite awareness. The effect size favoured neither Bispectral Index monitoring nor standard clinical and electronic monitoring, with little precision in the OR estimate for the combination of definite and possible awareness (OR 0.96, 95% CI 0.35 to 2.65). The effect size favoured Bispectral Index monitoring for definite awareness, but with little precision in the OR estimate (OR 0.60, 95% CI 0.13 to 2.75). We performed three smaller meta‐analyses of anaesthetic drugs. There were nine studies with 1290 participants. Wakefulness was reduced by ketamine and etomidate compared to thiopental. Wakefulness was more frequent than awareness. Benzodiazepines reduces awareness compared to thiopental, ketamine, and placebo., Also, higher doses of inhaled anaesthetics versus lower doses reduced the risk of awareness. We graded the quality of the evidence as low or very low in the 'Summary of findings' tables for the five comparisons. Most of the secondary outcomes in this review were not reported in the included RCTs. Authors' conclusions Anaesthetic depth monitors may have similar effects to standard clinical and electrical monitoring on the risk of awareness during surgery. In older studies comparing anaesthetics in a smaller portion of the patient sample, wakefulness occurred more frequently than awareness. Use of etomidate and ketamine lowered the risk of wakefulness compared to thiopental. Benzodiazepines compared to thiopental and ketamine, or higher doses of inhaled anaesthetics versus lower doses, reduced the risk of awareness.

Forty patients undergoing coronary artery bypass grafting were studied, of whom 24 had depressed global left ventricular (LV) function at preoperative catheterization, to evaluate the effects of midazolam on LV pump performance and contractility.Transesophageal echocardiography and simultaneous hemodynamic measurements were used to assess LV preload, afterload, and systolic performance during inhalation of 100% O₂ and after 0.1 mg/kg of midazolam. Systolic function indices were expressed as a percent of the predicted value for observed end-systolic stress to estimate LV contractility. In the entire study population, midazolam did not affect cardiac index. Heart rate and mean arterial pressure were reduced (63 +/- 13 to 59 +/- 12 bm; P < 0.0006 and 89 +/- 15 to 76 +/- 16 mm Hg; P < 0.0001) as were pulmonary capillary wedge pressure, central venous pressure, and systemic and pulmonary vascular resistance. Afterload, as measured by end-systolic stress, was reduced (55 +/- 33 to 48 +/- 26 kdyne/cm (²); P = 0.007) with no change in fractional shortening or percent area change. As a result, systolic function decreased in relation to observed end-systolic stress, providing evidence of reduced LV contractility. Thus, midazolam administration (0.1 mg/kg) caused no change in cardiac pump performance but decreased LV contractility in the entire population. Myocardial contractility was lower at baseline and after the administration of midazolam in the depressed ejection fraction group, but the decrease in contractility was not exaggerated in the depressed ejection fraction group. Thus, mild adverse myocardial effects of midazolam appear to be offset by induced reduction of afterload, and are not more severe in high-risk patients with depressed preoperative left ventricular ejection fraction. (Anesth Analg 1995;81:793-9)

Simultaneous hemodynamic measurements were used to assess LV preload, afterload, and systolic performance during inhalation of 100% oxygen (O2) and 60% N2O:40% O2. Systolic function indices were expressed as a percent of the predicted value for observed end-systolic stress to provide estimates of LV contractility. In the entire study population, N2O reduced pump performance (cardiac index 2.4 ± 0.8 to 2.2 ± 0.6 L·min−1·m−2; P < 0.02). Heart rate and mean arterial pressure were reduced (67 ± 13 to 64 ± 13, P < 0.01, and 87 ± 9 to 80 ± 15, P < 0.005) as were left and right ventricular stroke work index. Preload, as measured by end-diastolic stress, was unchanged but afterload, as measured by end-systolic stress, tended to decrease (88 ± 31 to 78 ± 28, P = 0.053). In the 13 patients with normal preoperative LV function, mean arterial pressure and LV stroke work index decreased significantly (91 ± 8 to 84 ± 14, P < 0.04, and 40 ± 13 to 34 ± 10, P < 0.04, respectively) and end-systolic stress tended to decrease (P = 0.054). In the depressed LV function group, central venous pressure increased and cardiac index and right ventricular stroke work index decreased (9 ± 3 to 10 ± 4, P < 0.02; 2.2 ± 0.6 to 2.0 ± 0.5, P < 0.01; and 4.3 ± 2.6 to 3.1 ± 1.9, P < 0.02, respectively). Despite decreases in end-systolic stress in both groups, during N2O inhalation differences between the normal and depressed LV function groups became evident with respect to fractional shortening and percent of area change (27 ± 8 vs 18 ± 6%; P < 0.002, and 46 ± 12 vs 33 ± 9%, P < 0.002, respectively) that were not detected during O2 inhalation. In parallel, significant differences in fractional shortening and percent of area change as a percent of that predicted from end-systolic stress during O2 inhalation increased between groups after N2O inhalation (82% vs 62% and 85% vs 66%, both P < 0.005). Thus, inhalation of 60% N2O:40% O2 caused a small but statistically significant reduction in cardiac pump performance, and exacerbated depressed myocardial contractility in patients with depressed preoperative LV function. Although no adverse clinical consequences were observed, assessment of whether newer anesthetic regimens better preserve function of the diseased left ventricle is warranted. Address correspondence and reprint requests to Anthony G. Messina, MD, Department of Anesthesiology, Lenox Hill Hospital, 100 East 77th Street, New York City, NY 10021. The authors would like to acknowledge Dr. John Savarese for his critical reading of this paper, Alan Van Poznak, MD, and Joseph F. Artusio, Jr., MD, for their encouragement and support, and Drs. Marjorie Topkins, Karl Krieger, and O. Wayne Isom for generously allowing us to enter their patients into our study. This paper is dedicated to my late father, Dr. John Messina, whose dedication to his patients served as a role model for me. Accepted for publication June 18, 1993. © 1993 International Anesthesia Research Society...

Iac repolarization in the absence of ischemic left ventricular regional wall motion abnormalities. We evaluated the association between ECG changes and left ventricular regional wall motion abnormalities detected by the echocardiograms performed before and after ECT in 11 patients. Immediately after ECT, three patients' ECGs revealed 1-mm downsloping or horizontal ST segment depression, one had a nonspecific ECG change (peaked T waves), and the ECG remained normal in seven. All patients had normal baseline echocardiograms. After ECT, at a time when the product of arterial blood pressure and heart rate was 100% above baseline values, five patients developed new left ventricular regional wall motion abnormalities that were confined to hypokinesia; no patient developed myocardial infarction or angina after ECT. Three patients with regional wall motion abnormalities developed ECG ST segment depression after ECT (sensitivity 60%), one had a nonspecific ECG change (peaked T waves), and the ECG of one patient remained normal. In conclusion, ECT may induce ECG changes with simultaneous regional wall motion abnormalities at a time when arterial blood pressure and heart rate are markedly elevated, findings that are highly suggestive of “demand” myocardial ischemia. In this small series, ECG or echocardiographic abnormalities did not predict clinical cardiac morbidity. Address correspondence to Dr. Messina, Department of Anesthesiology, Lenox Hill Hospital, 100 East 77th Street, New York, NY 10021. Accepted for publication May 18, 1992. © 1992 International Anesthesia Research Society...