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The article focuses on the advancement of pharmacologic computer simulation which greatly improved the application of pharmacokinetics and pharmacodynamic models. It discusses the parameters involved in the development of pharmacokinetic and pharmacodynamic models. It also presents the clinical implications of the combined application of the pharmacokinetics and pharmacodynamic models to predict the drug concentrations and its drug effect with the use of computer simulation.

Oxygen inhalation is recommended for the initial care of trauma victims. The improved survival seen in early hemorrhage is normally associated with an increase in blood pressure. Although clinical use of oxygen can occur late after hemorrhage, the effects of late administration have not been specifically examined. Anesthetized rats were studied using an isobaric hemorrhage model with target pressures of either 70 or 40 mmHg. At various times after hemorrhage, the feedback control of the blood pressure was stopped and the inspired gas was changed from room air to 100% oxygen. The results show that shortly after hemorrhage to 70 mmHg, oxygen inhalation results in an increase in mean arterial blood pressure of 60 ± 3 mmHg, which is associated with a large increase in total peripheral resistance from 0.89 ± 0.05 to 1.25 ± 0.1 peripheral resistance units. The blood pressure response is essentially unchanged with time, and it is not altered by a 10-min exposure to NG-nitro-L-arginine methyl ester. At a target pressure of 40 mmHg, the initial blood pressure response to oxygen is the same, but it gradually decreases as the animal develops a lactic acidosis. We conclude that the therapeutic value of oxygen needs to be separately evaluated for late hemorrhage. [ABSTRACT FROM AUTHOR]

The evidence supporting the intraoperative use of processed electroencephalography (pEEG) monitoring to guide anesthetic delivery is growing rapidly. This article reviews the key features of electroencephalography (EEG) waveforms and their clinical implications in select patient populations and anesthetic techniques. The first patient topic reviewed is the vulnerable brain. This term has emerged as a description of patients who may exhibit increased sensitivity to anesthetics and/or may develop adverse neurocognitive effects following anesthesia. pEEG monitoring of patients who are known to have or are suspected of having vulnerable brains, with focused attention on the suppression ratio, alpha band power, and pEEG indices, may prove useful. Second, pEEG monitoring along with vigilant attention to anesthetic delivery may minimize the risk of intraoperative awareness when administering a total intravenous anesthesia in combination with a neuromuscular blockade. Third, we suggest that processed EEG monitoring may play a role in anesthetic and resuscitative management when adverse changes in blood pressure occur. Fourth, pEEG monitoring can be used to better identify anesthesia requirements and guide anesthetic titration in patients with known or suspected substance use. [ABSTRACT FROM AUTHOR]

Background: There is insufficient prospective evidence regarding the relationship between surgical experience and prolonged opioid use and pain. The authors investigated the association of patient characteristics, surgical procedure, and perioperative anesthetic course with postoperative opioid consumption and pain 3 months postsurgery. The authors hypothesized that patient characteristics and intraoperative factors predict opioid consumption and pain 3 months postsurgery. Methods: Eleven U.S. and one European institution enrolled patients scheduled for spine, open thoracic, knee, hip, or abdominal surgery, or mastectomy, in this multicenter, prospective observational study. Preoperative and postoperative data were collected using patient surveys and electronic medical records. Intraoperative data were collected from the Multicenter Perioperative Outcomes Group database. The association between postoperative opioid consumption and surgical site pain at 3 months, elicited from a telephone survey conducted at 3 months postoperatively, and demographics, psychosocial scores, pain scores, pain management, and case characteristics, was analyzed. Results: Between September and October 2017, 3,505 surgical procedures met inclusion criteria. A total of 1,093 cases were included; 413 patients were lost to follow-up, leaving 680 (64%) for outcome analysis. Preoperatively, 135 (20%) patients were taking opioids. Three months postsurgery, 96 (14%) patients were taking opioids, including 23 patients (4%) who had not taken opioids preoperatively. A total of 177 patients (27%) reported surgical site pain, including 45 (13%) patients who had not reported pain preoperatively. The adjusted odds ratio for 3-month opioid use was 18.6 (credible interval, 10.3 to 34.5) for patients who had taken opioids preoperatively. The adjusted odds ratio for 3-month surgical site pain was 2.58 (1.45 to 4.4), 4.1 (1.73 to 8.9), and 2.75 (1.39 to 5.0) for patients who had site pain preoperatively, knee replacement, or spine surgery, respectively. Conclusions: Preoperative opioid use was the strongest predictor of opioid use 3 months postsurgery. None of the other variables showed clinically significant association with opioid use at 3 months after surgery. In these prospectively collected cohort data, preoperative opioid use was identified as the strongest risk factor for opioid use at 3 months postoperatively. No correlation was found between persistent opioid use at 3 months and surgical site pain at 3 months. No association was identified between preoperative anxiety, preoperative depression, or surgery type and opioid use at 3 months in multivariable models, although credible intervals were large for some variables. [ABSTRACT FROM AUTHOR]

BACKGROUND: Undetected apnea can lead to severe hypoxia, bradycardia, and cardiac arrest. Tracheal sounds entropy has been proved to be a robust method for estimating respiratory flow, thus maybe a more reliable way to detect obstructive and central apnea during sedation. METHODS: A secondary analysis of a previous pharmacodynamics study was conducted. Twenty volunteers received propofol and remifentinal until they became unresponsive to the insertion of a bougie into the esophagus. Respiratory flow rate and tracheal sounds were recorded using a pneumotachometer and a microphone. The logarithm of the tracheal sound Shannon entropy (Log-E) was calculated to estimate flow rate. An adaptive Log-E threshold was used to distinguish between the presence of normal breath and apnea. Apnea detected from tracheal sounds was compared to the apnea detected from respiratory flow rate. RESULTS: The volunteers stopped breathing for 15 s or longer (apnea) 322 times during the 12.9-h study. Apnea was correctly detected 310 times from both the tracheal sounds and the respiratory flow. Periods of apnea were not detected by the tracheal sounds 12 times. The absence of tracheal sounds was falsely detected as apnea 89 times. Normal breathing was detected correctly 1,196 times. The acoustic method detected obstructive and central apnea in sedated volunteers with 95% sensitivity and 92% specificity. CONCLUSIONS: We found that the entropy of the acoustic signal from a microphone placed over the trachea may reliably provide an early warning of the onset of obstructive and central apnea in volunteers under sedation. [ABSTRACT FROM AUTHOR]

Background: Opioids are commonly used in conjunction with sedative drugs to provide anesthesia. Previous studies have shown that opioids reduce the clinical requirements of sedatives needed to provide adequate anesthesia. Processed electroencephalographic parameters, such as the Bispectral Index (BIS; Aspect Medical Systems, Newton, MA) and Auditory Evoked Potential Index (AAI; Alaris Medical Systems, San Diego, CA), can be used intraoperatively to assess the depth of sedation. The aim of this study was to characterize how the addition of opioids sufficient to change the clinical level of sedation influenced the BIS and AAI.Methods: Twenty-four adult volunteers received a target-controlled infusion of remifentanil (0-15 ng/ml) and inhaled sevoflurane (0-6 vol%) at various target concentration pairs. After reaching pseudo-steady state drug levels, the modified Observer's Assessment of Alertness/Sedation score, BIS, and AAI were measured at each target concentration pair. Response surface pharmacodynamic interaction models were built using the pooled data for each pharmacodynamic endpoint.Results: Response surface models adequately characterized all pharmacodynamic endpoints. Despite the fact that sevoflurane-remifentanil interactions were strongly synergistic for clinical sedation, BIS and AAI were minimally affected by the addition of remifentanil to sevoflurane anesthetics.Conclusion: Although clinical sedation increases significantly even with the addition of a small to moderate dose of remifentanil to a sevoflurane anesthetic, the BIS and AAI are insensitive to this change in clinical state. Therefore, during "opioid-heavy" sevoflurane-remifentanil anesthetics, targeting a BIS less than 60 or an AAI less than 30 may result in an unnecessarily deep anesthetic state. [ABSTRACT FROM AUTHOR]

A patient who manifested signs of serotonin syndrome during an intravenous anesthetic with remifentanil and propofol is presented. The patient displayed lower extremity clonus, nystagmus, and diaphoresis. At the time of surgery, the patient was being treated with fluoxetine (a selective serotonin reuptake inhibitor). A presumptive diagnosis of serotonin syndrome was made intraoperatively and all opioids were discontinued. His symptoms resolved in the Postanesthesia Care Unit without incident. [ABSTRACT FROM AUTHOR]