Rolf Sandin

Reduction in the incidence of awareness using BIS monitoring

Background:  Explicit recall (ER) is evident in approximately 0.2% of patients given general anaesthesia including muscle relaxants. This prospective study was performed to evaluate if cerebral monitoring using BIS to guide the conduction of anaesthesia could reduce this incidence significantly.

Mortality Within 2 Years After Surgery in Relation to Low Intraoperative Bispectral Index Values and Preexisting Malignant Disease

BACKGROUND: A correlation between deep anesthesia (defined as time with Bispectral Index (BIS) <45; TBIS <45) and death within 1 yr after surgery has previously been reported. In order to confirm or refute these findings, we evaluated TBIS <45 as an independent risk factor for death within 1 and 2 yr after surgery and also the impact of malignancy, the predominant cause of death in the previous report. METHODS: Mortality within 2 yr after surgery, causes of death and the occurrence of malignant disease at the time of surgery were identified in a cohort of 4087 BIS-monitored patients. Statistically significant univariate predictors of mortality were identified. In order to allow for comparison with previous data, the following multivariate analysis was first done without, and thereafter with, preexisting malignancy status, the predominant cause of death. RESULTS: One-hundred-seventy-four (4.3%) patients died within 1 yr and another 92 during the second year (totaling 6.5% in 2 yr). TBIS <45 was a significant predictor of 1- and 2-yr mortality when preexisting malignant disease was not among the co-variates (hazard ratio [HR] 1.13 [1.01–1.27] and 1.18 [1.08–1.29], respectively). Further exploration confined the significant relation between postoperative mortality and TBIS <45 to patients with preexisting malignant diagnoses associated with extensive surgery and less favorable prognosis. The most powerful predictors of 2-yr mortality in the model, including preexisting malignancy, were ASA physical score class IV (HR 19.3 [7.31–51.1]), age >80 yr (HR 2.93 [1.79–4.79]), and preexisting malignancy associated with less favorable prognosis (HR 9.30 [6.60–13.1]).When the initial multivariate regression was repeated using preexisting malignancy status among the co-variates in the model, the previously significant relation between 1, and 2-yr mortality and TBIS <45 did not reach statistical significance. CONCLUSION: Using a similar set of co-variates as in previous work, we confirmed the statistical relation between 1-yr mortality and TBIS <45, and we extended this observation to 2-yr mortality. However, this relation is sensitive to the selection of co-variates in the statistical model, and a randomized study is required to demonstrate that there really is a causal impact from and TBIS <45 on postoperative mortality and, if it does, the effect is probably very weak in comparison with co-morbidity as assessed by ASA physical score, the preexisting malignancy status at surgery and age.

Victims of awareness

Background: Intraoperative awareness with explicit recall may be followed by long‐lasting mental symptoms. However, the average risk for developing mental sequelae after awareness, and the average severity and the duration of symptoms has not previously been illustrated in a consecutive series of awareness cases.

Late Psychological Symptoms after Awareness among Consecutively Included Surgical Patients

Background:Awareness during general anesthesia can cause late psychological symptoms. Selection bias may have affected the results in previous retrospective studies. The authors used prospective consecutive collection to recruit patients with previous awareness. Methods:In a cohort of 2,681 consecutive patients scheduled to undergo general anesthesia, 98 considered themselves to have been aware during previous surgery. Six patients died before inclusion, and another 13 were excluded (4 cases of stoke or dementia, 7 declined to participate, and 2 could not be located). Seventy-nine patients were interviewed by telephone, and medical records were checked in uncertain cases. The interview followed a structured protocol, including seven late symptoms (anxiety, chronic fear, nightmares, flashbacks, indifference, loneliness, and lack of confidence in future life). Three persons independently assessed the interviews for classification, to determine whether awareness had occurred. Results:Four cases were performed using regional anesthesia, and another 29 were not considered as awareness by the assessors. Therefore, the final analyses included 46 patients. Twenty (43%) had experienced pain, and 30 (65%) described acute emotional reactions during the awareness episode. Fifteen (33%) patients had experienced late psychological symptoms afterward. In 6 of those cases, the symptoms lasted for more than 2 months, and 1 patient had a diagnosis of post–traumatic stress disorder. Acute emotional reactions were significantly related to late psychological symptoms (P < 0.05). Conclusion:The method for recruiting awareness cases in studies on late psychological symptoms may affect the result. The authors found fewer and milder problems, despite a similar degree of initial problems as in previous studies.

Spectral entropy monitoring is associated with reduced propofol use and faster emergence in propofol-nitrous oxide-alfentanil anesthesia.

Background:This multicenter study evaluated the effect of a new depth of anesthesia–monitoring device based on time-frequency–balanced spectral entropy of electroencephalogram monitoring (GE Healthcare Finland, Helsinki, Finland) on consumption of anesthetic drugs and recovery times after anesthesia. Methods:The study was a prospective, randomized, single-blind study performed in six hospitals in Finland, Sweden, and Norway. After institutional review board approval and written informed consent from each patient, the patients were randomly allocated to anesthesia with entropy values either shown (entropy group) or not shown (control group). Anesthesia was maintained with propofol, nitrous oxide, and alfentanil. In the entropy group, propofol was given to keep the state entropy value between 45 and 65, and alfentanil was given to keep the state entropy–response entropy difference below 10 units and heart rate and blood pressure within ±20% of the baseline values. The control group patients were anesthetized to keep heart rate and blood pressure within ±20% of the baseline values. Statistical methods included Mann–Whitney U test and unpaired t tests. Results:A total of 368 patients were studied. In the entropy group, entropy values were higher during the whole operation and especially during the last 15 min (P < 0.001). Consequently, propofol consumption was smaller in the entropy group during the whole anesthesia period (P < 0.001) and especially during the last 15 min (P < 0.001). This shortened the time delay in the early recovery parameters in the entropy group. Conclusion:Entropy monitoring assisted titration of propofol, especially during the last part of the procedures, as indicated by higher entropy values, decreased consumption of propofol, and shorter recovery times in the entropy group.

Pharyngeal function and airway protection during subhypnotic concentrations of propofol, isoflurane, and sevoflurane: volunteers examined by pharyngeal videoradiography and simultaneous manometry

Background Anesthetic agents alter pharyngeal function with risk of impaired airway protection and aspiration. This study was performed to evaluate pharyngeal function during subhypnotic concentrations of propofol, isoflurane, and sevoflurane and to compare the drugs for possible differences in this respect. Methods Forty-five healthy volunteers were randomized to receive propofol, isoflurane, or sevoflurane. During series of liquid contrast bolus swallowing, fluoroscopy and simultaneous solid state videomanometry was used to study the incidence of pharyngeal dysfunction, the initiation of swallowing, and the bolus transit time. Pressure changes were recorded at the back of the tongue, the pharyngeal constrictor muscles, and the upper esophageal sphincter. After control recordings, the anesthetic was delivered, and measurements were made at 0.50 and 0.25 predicted blood propotol concentration (Cp50asleep) for propofol and 0.50 and 0.25 minimum alveolar concentration (MAC)awake for the inhalational agents. Final recordings were made 20 min after the end of anesthetic delivery. Results All anesthetics caused an increased incidence of pharyngeal dysfunction with laryngeal bolus penetration. Propofol increased the incidence from 8 to 58%, isoflurane from 4 to 36%, and sevoflurane from 6 to 35%. Propofol in 0.50 and 0.25 Cp50asleep had the most extensive effect on the pharyngeal contraction patterns (P < 0.05). The upper esophageal sphincter resting tone was markedly reduced from 83 ± 36 to 39 ± 19 mmHg by propofol (P < 0.001), which differed from isoflurane (P = 0.03). Sevoflurane also reduced the upper esophageal sphincter resting tone from 65 ± 16 to 45 ± 18 mmHg at 0.50 MACawake (P = 0.008). All agents caused a reduced upper esophageal sphincter peak contraction amplitude (P < 0.05), and the reduction was greatest in the propofol group (P = 0.002). Conclusion Subhypnotic concentrations of propofol, isoflurane, and sevoflurane cause an increased incidence of pharyngeal dysfunction with penetration of bolus to the larynx. The effect on the pharyngeal contraction pattern was most pronounced in the propofol group, with markedly reduced contraction forces.

Association of Anesthesia and Surgery During Childhood With Long-term Academic Performance

Importance The results of preclinical studies suggest that anesthetic drugs administered to neonatal animals cause widespread neuronal apoptosis and later neurocognitive impairment. Adequately powered studies in the pediatric surgical population are scarce, and it is unclear whether such preclinical findings are relevant for the pediatric setting. Objective To examine the association of anesthesia and surgery before age 4 years with long-term academic and cognitive performance indexed by school grades at age 16 years and IQ test scores at military conscription. Design, Setting, and Participants This investigation was a cohort study among all children born in Sweden between January 1973 and December 1993. The dates of analysis were April 2013 to October 2015. Among all 2 174 073 Swedish children born between 1973 and 1993, we identified a primary study cohort of 33 514 children with 1 anesthesia and surgery exposure before age 4 years and no subsequent hospitalization and 159 619 matched unexposed control children. In addition, 3640 children with multiple surgical procedures before age 4 years were studied. Exposure Having at least 1 surgical procedure in the Swedish Patient Register before age 4 years. Main Outcomes and Measures The mean school grades at age 16 years and IQ test scores at military conscription at age 18 years. The mean difference between the exposed cohort and unexposed cohort was estimated in a model that included sex, month of birth during the same year, gestational age at delivery, Apgar score at 5 minutes, maternal and paternal educational levels, annual taxable household income, cohabiting parents, and number of siblings. Results Among 33 514 exposed children (22 484 male and 11 030 female) and 159 619 unexposed children (105 812 male and 53 807 female) in the primary study cohort, 1 exposure before age 4 years was associated with a mean difference of 0.41% (95% CI, 0.12%-0.70%) lower school grades and 0.97% (95% CI, 0.15%-1.78%) lower IQ test scores. The magnitude of the difference was the same after multiple exposures. There was no difference in school grades with 1 exposure before ages 6 months, 7 to 12 months, 13 to 24 months, or 25 to 36 months. The overall difference was markedly less than the differences associated with sex, maternal educational level, or month of birth during the same year. Conclusions and Relevance Exposure to anesthesia and surgery before age 4 years has a small association with later academic performance or cognitive performance in adolescence on a population level. While more vulnerable subgroups of children may exist, the low overall difference in academic performance after childhood exposure to surgery is reassuring. These findings should be interpreted in light of potential adverse effects of postponing surgery.

The effect of neuromuscular block and noxious stimulation on hypnosis monitoring during sevoflurane anesthesia.

BACKGROUND:There are conflicting results on the influence of neuromuscular block (NMB) on the bispectral index (BIS). We investigated the influence of two degrees of NMB on BIS, Alaris auditory-evoked potential index (AAI), and the electromyogram (EMG) obtained with needle electrodes from the frontal and temporal muscles, immediately adjacent to the BIS-sensor. METHODS:Twenty patients were anesthetized with sevoflurane, titrated for 30 min to an end-tidal concentration of 1.2% (baseline). Rocuronium was infused to 50% (partial) and 95% (profound) depression of the first twitch in a train-of-four response, the order being randomly chosen. Noxious tetanic electrical stimulation was applied at four occasions: 1) at baseline (control measurement), 2 and 3) at each degree of NMB, and 4) after neostigmine reversal. BIS, AAI, and EMG were obtained 2 min before and 2 min after each noxious stimulation. RESULTS:Median BIS and AAI at baseline were 44 (39–50) and 15 (14–16), respectively. The two degrees of NMB did not affect BIS, AAI, and EMG before noxious stimulation. In contrast, profound NMB altered the BIS and AAI responses to noxious stimulation when compared with partial NMB, (BIS P = 0.01, AAI P < 0.01), after neostigmine reversal (BIS P < 0.01, AAI P = 0.01) and compared with baseline (BIS P = 0.08, AAI P = 0.02). No significant increase in EMG was found. CONCLUSION:BIS and AAI responses to noxious tetanic electrical stimulation are affected by the degree of NMB during sevoflurane anesthesia whereas NMB does not affect BIS or AAI in the absence of noxious stimulation.

A comparison of Bispectral index and rapidly extracted auditory evoked potentials index responses to noxious stimulation during sevoflurane anesthesia

In 21 patients given sevoflurane anesthesia, we simultaneously compared the abilities of Bispectral Index (BIS) and rapidly extracted auditory evoked potentials index (AAI) to display the effect of an increasing cerebral concentration of sevoflurane, with and without noxious stimulation. In addition to BIS/AAI, hemodynamic variables were monitored. After titrating sevoflurane to BIS = 50–55 during 15 min, the end-tidal concentration of sevoflurane (1.46% ± 0.20%) was doubled followed by a noxious stimulus, laryngoscopy, applied at random time points within the following 15 min. After the end-tidal concentration of sevoflurane was doubled, a substantial reduction in BIS was observed, whereas only a slight reduction in AAI was seen (P < 0.0001). BIS/AAI responses to laryngoscopy were not attenuated with increasing wash-in of sevoflurane. After noxious stimulation, AAI exceeded the highest recommended value, 25, in 3 cases, whereas BIS did not exceed the recommended threshold, 60, in any of the patients. Response times for BIS and AAI were 44.5 ± 26 and 47 ± 31 s, respectively. These results suggest that, at a hypnotic level associated with surgical sevoflurane anesthesia, BIS better displays drug-related alterations in the level of hypnosis than AAI or hemodynamic variables but there is no difference between BIS and AAI in the time to response to a noxious stimulus.

Malignant disease within 5 years after surgery in relation to duration of sevoflurane anesthesia and time with bispectral index under 45.

BACKGROUND:Surgery, general anesthesia, and related events have been implicated to promote cancer proliferation. We investigated the incidence of cancer within 5 years after surgery in relation to duration of anesthesia (TANESTH) and also by time with bispectral index (BIS) under 45 (TBIS<45) serving as a proxy for more profound anesthesia exposure. METHODS:New malignant diagnoses after surgery under sevoflurane anesthesia were obtained in a prospective cohort of 2972 BIS-monitored patients without any clinically diagnosed malignant disease at the time of index surgery. The risk of cancer during follow-up in relation to TANESTH and TBIS<45 was assessed by Cox regression. The cancer incidence in this surgical population was compared with the incidence in a standardized general population by calculation of standard incidence ratio. RESULTS:One hundred twenty-nine patients (4.3%) were assigned 136 new malignant diagnoses within 5 years after surgery. No relation between TANESTH or TBIS<45 and new malignant disease was found, nor were any significant relations obtained when other thresholds for BIS (i.e., <30, <40, and <50, respectively) were used in the calculations. The standard incidence ratio for new malignant disease was 1.37 (confidence interval, 1.15–1.62). CONCLUSION:Neither duration of anesthesia nor increased cumulative time with profound sevoflurane anesthesia was associated with an increased risk for new malignant disease within 5 years after surgery in previously cancer-free patients.