Eric Jacobsohn

Anesthesia awareness and the bispectral index.

BACKGROUND Awareness during anesthesia is a serious complication with potential long-term psychological consequences. Use of the bispectral index (BIS), developed from a processed electroencephalogram, has been reported to decrease the incidence of anesthesia awareness when the BIS value is maintained below 60. In this trial, we sought to determine whether a BIS-based protocol is better than a protocol based on a measurement of end-tidal anesthetic gas (ETAG) for decreasing anesthesia awareness in patients at high risk for this complication. METHODS We randomly assigned 2000 patients to BIS-guided anesthesia (target BIS range, 40 to 60) or ETAG-guided anesthesia (target ETAG range, 0.7 to 1.3 minimum alveolar concentration [MAC]). Postoperatively, patients were assessed for anesthesia awareness at three intervals (0 to 24 hours, 24 to 72 hours, and 30 days after extubation). RESULTS We assessed 967 and 974 patients from the BIS and ETAG groups, respectively. Two cases of definite anesthesia awareness occurred in each group (absolute difference, 0%; 95% confidence interval [CI], -0.56 to 0.57%). The BIS value was greater than 60 in one case of definite anesthesia awareness, and the ETAG concentrations were less than 0.7 MAC in three cases. For all patients, the mean (+/-SD) time-averaged ETAG concentration was 0.81+/-0.25 MAC in the BIS group and 0.82+/-0.23 MAC in the ETAG group (P=0.10; 95% CI for the difference between the BIS and ETAG groups, -0.04 to 0.01 MAC). CONCLUSIONS We did not reproduce the results of previous studies that reported a lower incidence of anesthesia awareness with BIS monitoring, and the use of the BIS protocol was not associated with reduced administration of volatile anesthetic gases. Anesthesia awareness occurred even when BIS values and ETAG concentrations were within the target ranges. Our findings do not support routine BIS monitoring as part of standard practice. (ClinicalTrials.gov number, NCT00281489 [ClinicalTrials.gov].).

Prevention of Intraoperative Awareness in a High-Risk Surgical Population

BACKGROUND Unintended intraoperative awareness, which occurs when general anesthesia is not achieved or maintained, affects up to 1% of patients at high risk for this complication. We tested the hypothesis that a protocol incorporating the electroencephalogram-derived bispectral index (BIS) is superior to a protocol incorporating standard monitoring of end-tidal anesthetic-agent concentration (ETAC) for the prevention of awareness. METHODS We conducted a prospective, randomized, evaluator-blinded trial at three medical centers. We randomly assigned 6041 patients at high risk for awareness to BIS-guided anesthesia (with an audible alert if the BIS value was <40 or >60, on a scale of 0 to 100, with 0 indicating the suppression of detectable brain electrical activity and 100 indicating the awake state) or ETAC-guided anesthesia (with an audible alert if the ETAC was <0.7 or >1.3 minimum alveolar concentration). In addition to audible alerts, the protocols included structured education and checklists. Superiority of the BIS protocol was assessed with the use of a one-sided Fishers exact test. RESULTS A total of 7 of 2861 patients (0.24%) in the BIS group, as compared with 2 of 2852 (0.07%) in the ETAC group, who were interviewed postoperatively had definite intraoperative awareness (a difference of 0.17 percentage points; 95% confidence interval [CI], -0.03 to 0.38; P=0.98). Thus, the superiority of the BIS protocol was not demonstrated. A total of 19 cases of definite or possible intraoperative awareness (0.66%) occurred in the BIS group, as compared with 8 (0.28%) in the ETAC group (a difference of 0.38 percentage points; 95% CI, 0.03 to 0.74; P=0.99), with the superiority of the BIS protocol again not demonstrated. There was no difference between the groups with respect to the amount of anesthesia administered or the rate of major postoperative adverse outcomes. CONCLUSIONS The superiority of the BIS protocol was not established; contrary to expectations, fewer patients in the ETAC group than in the BIS group experienced awareness. (Funded by the Foundation for Anesthesia Education and Research and others; BAG-RECALL ClinicalTrials.gov number, NCT00682825.).

Prevalence of undiagnosed obstructive sleep apnea among adult surgical patients in an academic medical center.

BACKGROUND Obstructive sleep apnea (OSA) affects approximately 20% of US adults, of whom about 90% are undiagnosed. While OSA may increase risk of perioperative complications, its prevalence among surgical patients is unknown. We tested the feasibility of screening surgical patients for OSA and determined the prevalence of undiagnosed OSA. METHODS In a prospective, observational study adult surgical patients were screened for OSA in an academic hospital. Patients without an OSA diagnosis who screened high-risk were offered a home sleep study to determine if they had OSA. The results were compared with polysomnography (PSG) when available. Charts of high-risk patients were examined for postoperative complications. High-risk patients received targeted interventions as part of a hospital safety initiative. RESULTS There were 2877 patients screened; 661 (23.7%) screened high-risk for OSA, of whom 534 (81%) did not have diagnosed OSA. The portable sleep study detected OSA in 170/207 (82%) high-risk patients without diagnosed OSA. Twenty-six PSGs confirmed OSA in 19 of these patients. Postoperatively there were no respiratory arrests, two unanticipated ICU admissions, and five documented respiratory complications. CONCLUSION Undiagnosed OSA is prevalent in adult surgical patients. Implementing universal screening is feasible and can identify undiagnosed OSA in many surgical patients. Further investigation is needed into perioperative complications and their prevention for patients with undiagnosed OSA.

Ischaemic preconditioning: mechanisms and potential clinical applications

PurposeBrief ischaemic episodes, followed by periods of reperfusion, increase the resistance to further ischaemic damage. This response is called “ischaemic preconditioning.” By reviewing the molecular basis and fundamental principals of ischaemic preconditioning, this paper will enable the anaesthetic and critical care practitioner to understand this developing therapeutic modality.SourceArticles were obtained from a Medline review (1960–1997; search terms: ischaemia, reperfusion injury, preconditioning, ischaemic preconditioning, cardiac protection). Other sources include review articles, textbooks, hand-searches (Index Medicus), and personal files.Principle findingIschaemic preconditioning is a powerful protective mechanism against ischaemic injury that has been shown to occur in a variety of organ systems, including the heart, brain, spinal cord, retina, liver; lung and skeletal muscle. Ischaemic preconditioning has both immediate and delayed protective effects, the importance of which varies between species and organ systems. While the exact mechanisms of both protective components are yet to be clearly defined, ischaemic preconditioning is a multifactorial process requiring the interaction of numerous signals, second messengers and effector mechanisms. Stimuli other than ischaemia, such as hypoxic perfusion, tachycardia and pharmacological agents, including isoflurane, have preconditioning-like effects. Currently ischaemic preconditioning is used during minimally invasive cardiac surgery without cardiopulmonary bypass to protect the myocardium against ischaemic injury during the anastomosis.ConclusionIschaemic preconditioning is a powerful protective mechanism against ischaemic injury in many organ systems. Future clinical applications will depend on the clarification of the underlying biochemical mechanisms, the development of pharmacological methods to induce preconditioning, and controlled trials in humans showing improved outcomes.RésuméObjectifDe brefs épisodes d’ischémie, suivis de périodes de reperfusion, accroissent la résistance à un dommage ischémique ultérieur. C’est ce qu’on appelle le «préconditionnement ischémique». En faisant un retour sur la base moléculaire et les principes fondamentaux du préconditionnement ischémique, le présent article fera mieux comprendre à l’anesthésiste et au praticien des soins intensifs les modalités de cette thérapeutique en évolution.Sources documentairesDes articles ont été obtenus à partir d’une recherche Medline (1960–1997; recherche de termes: ischémie, lésion de reperfusion, préconditionnement, préconditionnement ischémique, protection cardiaque). Les autres sources comprennent des articles de revues, des monographies, des recherches manuelles (Index Medicus) et une documentation personnelle.Données principalesLe préconditionnement ischémique est un mécanisme protecteur puissant contre la lésion ischémique qui se produit, selon l’expérience, dans divers systèmes organiques, incluant le coeur; le cerveau, la moelle épinière, la rétine, le foie, les poumons et les muscles squelettiques. Le préconditionnement présente deux effets protecteurs, l’un immédiat et l’autre différé, dont l’importance varie entre les espèces et les systèmes organiques. Quoique les mécanismes exacts des deux composantes protectrices n’aient pas encore été clairement définis, on sait que le préconditionnement ischémique est un processus multifactoriel nécessitant l’interaction de nombreux signaux, de seconds messagers et de mécanismes effecteurs. Des stimuli différents de l’ischémie, comme la perfusion hypoxique, la tachycardie et des agents pharmacologiques, comprenant l’isoflurane, ont des effets similaires au préconditionnement. Le préconditionnement ischémique est actuellement utilisé pendant la chirurgie cardiaque mini-effractive, sans circulation extracorporelle pour protéger le myocarde contre une lésion ischémique lors de l’anastomose.ConclusionLe préconditionnement ischémique est un mécanisme protecteur puissant contre les lésions ischémiques dans de nombreux systèmes organiques. Les applications cliniques éventuelles vont dépendre de la clarification des mécanismes biochimiques sous-jacents, de l’évolution des méthodes pharmacologiques d’induction du préconditionnement et des essais contrôlés chez les humains démontrant de meilleurs résultats.

Relationship between Bispectral Index Values and Volatile Anesthetic Concentrations during the Maintenance Phase of Anesthesia in the B-Unaware Trial

BACKGROUND Hypnotic depth during anesthesia affects electroencephalography waveforms and electroencephalogram-derived indices, such as the bispectral index (BIS). Titrating anesthetic administration against the BIS assumes reliable relationships between BIS values, electroencephalogram waveforms, and effect site concentration, beyond loss of responsiveness. Associations among BIS, end-tidal anesthetic concentrations (ETAC), and patient characteristics were examined during anesthetic maintenance, using B-Unaware trial data. METHODS Pharmacokinetically stable ETAC epochs during intraoperative anesthetic maintenance were analyzed. A generalized estimating equation determined independent relationships among BIS, ETAC (in age-adjusted minimum alveolar concentration equivalents), patient characteristics, and 1-yr mortality. Further individual and population characteristics were explored graphically. RESULTS A total of 3,347,523 data points from 1,100 patients were analyzed over an ETAC range from 0.42 to 1.51 age-adjusted minimum alveolar concentration. A generalized estimating equation yielded a best predictive equation: BIS = 62.9-1.6 (if age younger than 60 yr) -1.6 (if female) -2.5 (if American Society of Anesthesiologists physical status more than 3) -2.6 (if deceased at 1 yr) -2.5 (if N2O was not used) -1.4 (if midazolam dose more than 2 mg) -1.3 (if opioid dose more than 50 morphine equivalents) -15.4 × age-adjusted minimum alveolar concentration. Although a population relationship between ETAC and BIS was apparent, interindividual variability in the strength and reliability of this relationship was large. Decreases in BIS with increasing ETAC were not reliably observed. Individual-patient linear regression yielded a median slope of -8 BIS/1 age-adjusted minimum alveolar concentration (interquartile range -30, 0) and a median correlation coefficient of -0.16 (interquartile range -0.031, -0.50). CONCLUSIONS Independent of pharmacokinetic confounding, BIS frequently correlates poorly with ETAC, is often insensitive to clinically significant changes in ETAC, and is vulnerable to interindividual variability. BIS is therefore incapable of finely guiding volatile anesthetic titration during anesthetic maintenance.

A Randomized Study in Diabetic Patients Undergoing Cardiac Surgery Comparing Computer-Guided Glucose Management With a Standard Sliding Scale Protocol

OBJECTIVE The aim of this study was to compare a standard insulin protocol with a computer-guided glucose management system to determine which method achieves tighter glucose control. DESIGN A prospective, randomized trial. SETTING A cardiothoracic intensive care unit (ICU) in a large academic medical center. PARTICIPANTS Forty patients with diabetes mellitus who were scheduled for cardiac surgery. INTERVENTIONS After induction of anesthesia and for the first 9 hours in the ICU, each subject received a standardized infusion of a 10% glucose solution at a rate of 1.0 mL/kg/h (ideal body weight). The subjects were then randomized to have their glucose controlled by either a paper-based insulin protocol or by a computer-guided glucose management system (CG). The desired range for blood glucose was set between 90 and 150 mg/dL. MEASUREMENTS AND MAIN RESULTS There were no differences between groups in baseline characteristics. Patients in the CG group spent more time in the desired range during both the intraoperative phase (49% v 27%, p = 0.001) and the ICU phase (84% v 60%, p < 0.0001). There were no statistical differences between groups in the number of hypoglycemia episodes. CONCLUSIONS The computer-guided glucose management system achieved tighter blood glucose control than a standard paper-based protocol in diabetic patients undergoing cardiac surgery. However, the low proportion of blood glucose recordings within the desired range in both groups during the intraoperative period reflects the challenges associated with achieving normoglycemia during cardiac surgery.

Intrapatient reproducibility of the BISxp monitor

Background:The Bispectral Index (BIS) reportedly reflects anesthetic depth. It is recommended that anesthetic agents should be titrated to maintain the BIS between 40 and 60 arbitrary BIS units during anesthesia. For anesthesia providers to follow this recommendation, the monitor should be predictably affected by different anesthetic agents and have good interpatient and intrapatient reproducibility. The authors hypothesized that when two BISxp® devices (Aspect Medical Systems, Newton, MA) are placed concurrently on the same patient, their readings are concordant throughout the anesthetic period. Methods:Simultaneous BIS recordings from two BISxp® monitors were obtained during anesthesia at 5-s intervals from 12 participants. Results:In total 22,860 concurrent paired BIS readings were obtained. For 10.7% of the time, there were sustained periods of 30 s or greater where the readings suggested a different depth of anesthesia. For 6% of the time, there were sustained periods of 30 s or greater where the readings differed by 10 or more arbitrary BIS units. The regression coefficient (R2) for the two devices was 0.65 (range, 0.35–0.92). There was zero bias between the devices, and the 95% limits of agreement ranged between −18 and +17. Conclusion:A conflicting anesthetic management was suggested by the simultaneous BIS readings 10.7% of the time. These results suggest that BISxp® does not always provide a reproducible single number. Anesthesia providers should not rely exclusively on the BIS reading when assessing depth of anesthesia.

Parasternal block and local anesthetic infiltration with levobupivacaine after cardiac surgery with desflurane: the effect on postoperative pain, pulmonary function, and tracheal extubation times.

Early tracheal extubation has become common after cardiac surgery. Anesthetic techniques designed to achieve this goal can make immediate postoperative analgesia challenging. We conducted this randomized, placebo-controlled, double-blind study to investigate the effect of a parasternal block on postoperative analgesia, respiratory function, and extubation times. We enrolled 20 patients having cardiac surgery via median sternotomy; 17 patients completed the study. A de-sflurane-based, small-dose opioid anesthetic was used. Before sternal wire placement, the surgeons performed the parasternal block and local anesthetic infiltration of sternotomy and tube sites with either 54 mL of saline placebo or 54 mL of 0.25% levobupivacaine with 1:400,000 epinephrine. Effects on pain and respiratory function were studied over 24 h. Patients in the levobupivacaine group used significantly less morphine in the first 4 h after surgery (20.8 ± 6.2 mg versus 33.2 ± 10.9 mg in the placebo group; P = 0.013); they also had better oxygenation at the time of extubation. Four of nine in the placebo group needed rescue pain medication, versus none of eight in the levobupivacaine group (P = 0.08). Peak serum levobupivacaine concentrations were below potentially toxic levels in all patients (0.64 ± 0.43 &mgr;g/mL; range, 0.24–1.64 &mgr;g/mL). Parasternal block and local anesthetic infiltration of the sternotomy wound and mediastinal tube sites with levobupivacaine can be a useful analgesic adjunct for patients who are expected to undergo early tracheal extubation after cardiac surgery.

High spinal anesthesia for cardiac surgery: Effects on β-adrenergic receptor function, stress response, and hemodynamics

Background This double-blind, randomized, controlled trial examined the effect of high-dose intrathecal bupivacaine in combination with general anesthesia on atrial &bgr;-adrenergic receptor function, the stress response, and hemodynamics during coronary artery bypass graft surgery. Methods Thirty-eight patients were randomized to either control (n = 19) or intrathecal bupivacaine (ITB) groups (n = 19). Patients in the ITB group received 37.5 mg intrathecal hyperbaric bupivacaine before induction of general anesthesia. Control patients received an injection of local anesthetic into the skin and subcutaneous tissues (sham spinal). Comparisons were made between groups with respect to atrial receptor desensitization and down-regulation, in addition to circulating catecholamines and hemodynamics. Results In patients with cardiopulmonary bypass (CPB) times in excess of 1 h, the ITB group had significantly less atrial &bgr;-receptor dysfunction, as measured by maximal isproteronol, 50% maximal isoproterenol, sodium fluoride-stimulated activity, and zinterol stimulation assays of adenylyl cyclase activity (P ≤ 0.02) and &bgr;-adrenergic receptor density (P = 0.02). Serum epinephrine, norepinephrine, and cortisol concentrations were significantly lower in the ITB group, independent of CPB times (P < 0.0001, P < 0.001, and P < 0.05, respectively). ITB patients had a higher cardiac index and a lower pulmonary vascular resistance index in the post-CPB time period (P < 0.01 and P < 0.05, respectively). In the pre-CPB period, mean arterial pressure and systemic vascular resistance index were significantly lower in the ITB group. Conclusions High-dose intrathecal bupivacaine, when combined with general anesthesia, resulted in less &bgr;-receptor dysfunction and a lower stress response during coronary artery bypass graft surgery.

Concurrence of Intraoperative Hypotension, Low Minimum Alveolar Concentration, and Low Bispectral Index Is Associated with Postoperative Death

Background:An intraoperative concurrence of mean arterial pressure less than 75 mmHg, minimum alveolar concentration less than 0.8, and bispectral index less than 45 has been termed a “triple low” state. An association between triple low and postoperative mortality has been reported but was not replicated in a subsequent study. The authors pooled existing data from clinical trials to further evaluate the purported association in an observational study. Methods:This retrospective observational study included 13,198 patients from three clinical trials: B-Unaware, BAG-RECALL, and Michigan Awareness Control Study. Patients with greater than 15 not necessarily consecutive minutes of triple low were propensity matched to controls with similar characteristics and comorbidities. A multivariable Cox proportional hazards model was used to evaluate the association between triple low duration and postoperative mortality. Results:Thirty-day mortality was 0.8% overall, 1.9% in the triple low cohort, and 0.4% in the nontriple low cohort (odds ratio, 5.16; 95% CI, 4.21 to 6.34). After matching and adjusting for comorbidities, cumulative duration of triple low was significantly associated with an increased risk of mortality at 30 days (hazard ratio, 1.09; 95% CI, 1.07 to 1.11, per 15 min) and 90 days (hazard ratio, 1.09; 95% CI, 1.08 to 1.11, per 15 min). Conclusion:There is a weak independent association between the triple low state and postoperative mortality, and the propensity-matched analysis does not suggest that this is an epiphenomenon.