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In this Pro-Con article, we debate the merits of using quantitative neuromuscular blockade monitoring. Consensus guidelines recommend their use to guide the administration of nondepolarizing neuromuscular blockade and reversal agents. A major impediment to this guideline is that until recently, reliable quantitative neuromuscular blockade monitors have not been widely available. Without them, anesthesia providers have been trained with and are adept at using a variety of qualitative neuromuscular blockade monitors otherwise known as peripheral nerve stimulators. Although perhaps less accurate, anesthesia providers find them reliable and easy to use. They have a long track record of using them with the perception that their use leads to effective neuromuscular blockade reversal and minimizes clinically significant adverse events from residual neuromuscular blockade. In the recent past, 2 disruptive developments have called upon anesthesia care providers to reconsider their practice in neuromuscular blockade administration, reversal, and monitoring. These include: (1) commercialization of more reliable quantitative neuromuscular monitors and (2) widespread use of sugammadex, a versatile reversal agent of neuromuscular blockade. Sugammadex appears to be so effective at rapidly and effectively reversing even the deepest of neuromuscular blockades, and it has left anesthesia providers wondering whether quantitative monitoring is indeed necessary or whether conventional, familiar, and less expensive qualitative monitoring will suffice? This Pro-Con debate will contrast anesthesia provider perceptions with evidence surrounding the use of quantitative neuromuscular blockade monitors to explore whether quantitative neuromuscular monitoring (NMM) is just another technology solution looking for a problem or a significant advance in NMM that will improve patient safety and outcomes., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2022 International Anesthesia Research Society.)

Opioids may influence inflammation. We compared genes associated with pain and inflammation in patients who consumed opioids (3-120 mg of oral morphine equivalents per day) with those who did not for differential expression. White blood cells were assayed in 20 patients presenting for total lower extremity joint replacement. We focused on messenger ribonucleic acid expression of complement proteins. We report that the expression of a complement inhibitor, complement 4 binding protein A, was reduced, and the expression of a complement activator, complement factor D, was increased in opioid-consuming patients. We conclude that opioid consumption may influence expression of complement activators and inhibitors., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 International Anesthesia Research Society.)

Background: Opioid-induced respiratory depression (OIRD) is traditionally recognized by assessment of respiratory rate, arterial oxygen saturation, end-tidal CO2, and mental status. Although an irregular or ataxic breathing pattern is widely recognized as a manifestation of opioid effects, there is no standardized method for assessing ataxic breathing severity. The purpose of this study was to explore using a machine-learning algorithm for quantifying the severity of opioid-induced ataxic breathing. We hypothesized that domain experts would have high interrater agreement with each other and that a machine-learning algorithm would have high interrater agreement with the domain experts for ataxic breathing severity assessment., Methods: We administered target-controlled infusions of propofol and remifentanil to 26 healthy volunteers to simulate light sleep and OIRD. Respiration data were collected from respiratory inductance plethysmography (RIP) bands and an intranasal pressure transducer. Three domain experts quantified the severity of ataxic breathing in accordance with a visual scoring template. The Krippendorff alpha, which reports the extent of interrater agreement among N raters, was used to assess agreement among the 3 domain experts. A multiclass support vector machine (SVM) was trained on a subset of the domain expert-labeled data and then used to quantify ataxic breathing severity on the remaining data. The Vanbelle kappa was used to assess the interrater agreement of the machine-learning algorithm with the grouped domain experts. The Vanbelle kappa expands on the Krippendorff alpha by isolating a single rater-in this case, the machine-learning algorithm-and comparing it to a group of raters. Acceptance criteria for both statistical measures were set at >0.8. The SVM was trained and tested using 2 sensor inputs for the breath marks: RIP and intranasal pressure., Results: Krippendorff alpha was 0.93 (95% confidence interval [CI], 0.91-0.95) for the 3 domain experts. Vanbelle kappa was 0.98 (95% CI, 0.96-0.99) for the RIP SVM and 0.96 (0.92-0.98) for the intranasal pressure SVM compared to the domain experts., Conclusions: We concluded it may be feasible for a machine-learning algorithm to quantify ataxic breathing severity in a manner consistent with a panel of domain experts. This methodology may be helpful in conjunction with traditional measures to identify patients experiencing OIRD.

The need to reduce the dose of intravenous anesthetic in the setting of hemorrhagic shock is a well-established clinical dogma. Considered collectively,; the body of information concerning the behavior of intravenous anesthetics during hemorrhagic shock, drawn from animal and human data, confirms that clinical dogma and informs the rational selection and administration of intravenous anesthetics in the setting of hemorrhagic shock. The physiologic changes during hemorrhagic shock can alter pharmacokinetics and pharmacodynamics of intravenous anesthetics. Decreased size of the central compartment and central clearance caused by shock physiology lead to an altered dose-concentration relationship. For most agents and adjuncts, shock leads to substantially higher concentrations and increased effect. The notable exception is etomidate, which has relatively unchanged pharmacokinetics during shock. Increased concentrations lead to increased primary effect as well as increased side effects, notably cardiovascular effects. Pharmacokinetic changes are essentially reversed for all agents by fluid resuscitation. Propofol is unique among agents in that, in addition to the pharmacokinetic changes, it exhibits increased potency during shock. The pharmacodynamic changes of propofol persist despite fluid resuscitation. The persistence of these pharmacodynamic changes during shock is unlikely to be due to increased endogenous opiates, but is most likely due to increased fraction of unbound propofol. The stage of shock also appears to influence the pharmacologic changes. The changes are more rapid and pronounced as shock physiology progresses to the uncompensated stage. Although scant, human data corroborate the findings of animal studies. Both the animal and human data inform the rational selection and administration of intravenous anesthetics in the setting of hemorrhagic shock. The well-entrenched clinical dogma that etomidate is a preferred induction agent in patients experiencing hemorrhagic shock is firmly supported by the evidence. Propofol is a poor choice for induction or maintenance of anesthesia in severely bleeding patients, even with resuscitation; this can include emergent trauma cases or scheduled cases that routinely have mild or moderate blood loss.

Gene variants may contribute to individual differences in the experience of pain and the efficacy and reward of treatments. We explored gene variation in opioid-naïve and opioid-consuming patients undergoing elective lower extremity total joint replacement. We focused on 3 gene pathways including prostaglandin, gamma-aminobutyric acid (GABA)-ergic reward, and hepatic metabolism pathways. We report that for genes with possible or probable deleterious impact in these 3 pathways, opioid consumers had more gene variants than opioid-naïve patients (median 3 vs 1, P = .0092). We conclude that chronic opiate users may have genetic susceptibility to altered responses in reward/dependency and pain/inflammation pathways.

Background: Numerous technologies are used to monitor respiratory rates in nonintubated patients. No technology has emerged as the standard. The primary aim of this study was to assess the limits of agreement between a reference sensor signal (respiratory inductance plethysmography bands) and 7 alternative sensor signals (nasal capnometer, nasal pressure transducer, oronasal thermistor, abdominal accelerometer, transpulmonary electrical impedance, peritracheal microphone, and photoplethysmography) for measuring low respiratory rates in sedated, nonintubated, supine volunteers. A unified approach based on a single breath detection algorithm was applied to each sensor to facilitate comparison. We hypothesized that all of the sensor signals would allow detection of low (<10 breaths per minute) respiratory rates to within ±2 breaths per minute of the reference sensor signal., Methods: Volunteers received remifentanil and propofol infusions at selected target concentration pairs to induce depression of ventilation. Signals from each sensor were analyzed by an identical threshold-based detection algorithm to compute the breathing rate. Bland-Altman limits of agreement and error rate analyses were used to characterize the performance of each sensor compared to the reference sensor., Results: The analysis of the accelerometer and capnometer signals, using Bland-Altman and error rate analyses, showed the highest breath rate agreement (1.96 × standard deviation) of the 7 sensors with -2.1 to 2.2 and -2.5 to 2.7 breaths per minute, respectively. All other signals exhibited wider limits of agreement, with impedance being the widest at -7.8 to 7.4 breaths per minute. For the abdomen accelerometer, 95% of Bland-Altman data points were within ±2 breaths per minute. For the capnometer, 96% of data points were within ±2 breaths per minute. Nasal pressure, thermistor, and microphone all had >80% of data points within ±2 breaths per minute. Impedance and photoplethysmograph signals had 58% and 64%, respectively., Conclusions: A unified approach can be applied to a variety of sensor signals to estimate respiratory rates in spontaneously breathing, nonintubated, sedated volunteers. However, detecting clinically relevant low respiratory rates (<6 breaths per minute) is a technical challenge. By our analysis, no single sensor was able to detect slow respiratory rates with adequate precision (<±2 breaths per minute of the reference signal). Of the sensors evaluated, capnometers and abdominal accelerometers may be the most reliable sensors for identifying hypopnea and central apnea.

Background: In patients who receive a nondepolarizing neuromuscular blocking drug (NMBD) during anesthesia, undetected postoperative residual neuromuscular block is a common occurrence that carries a risk of potentially serious adverse events, particularly postoperative pulmonary complications. There is abundant evidence that residual block can be prevented when real-time (quantitative) neuromuscular monitoring with measurement of the train-of-four ratio is used to guide NMBD administration and reversal. Nevertheless, a significant percentage of anesthesiologists fail to use quantitative devices or even conventional peripheral nerve stimulators routinely. Our hypothesis was that a contributing factor to the nonutilization of neuromuscular monitoring was anesthesiologists' overconfidence in their knowledge and ability to manage the use of NMBDs without such guidance., Methods: We conducted an Internet-based multilingual survey among anesthesiologists worldwide. We asked respondents to answer 9 true/false questions related to the use of neuromuscular blocking drugs. Participants were also asked to rate their confidence in the accuracy of each of their answers on a scale of 50% (pure guess) to 100% (certain of answer)., Results: Two thousand five hundred sixty persons accessed the website; of these, 1629 anesthesiologists from 80 countries completed the 9-question survey. The respondents correctly answered only 57% of the questions. In contrast, the mean confidence exhibited by the respondents was 84%, which was significantly greater than their accuracy. Of the 1629 respondents, 1496 (92%) were overconfident., Conclusions: The anesthesiologists surveyed expressed overconfidence in their knowledge and ability to manage the use of NMBDs. This overconfidence may be partially responsible for the failure to adopt routine perioperative neuromuscular monitoring. When clinicians are highly confident in their knowledge about a procedure, they are less likely to modify their clinical practice or seek further guidance on its use.

A panel of clinician scientists with expertise in neuromuscular blockade (NMB) monitoring was convened with a charge to prepare a consensus statement on indications for and proper use of such monitors. The aims of this article are to: (a) provide the rationale and scientific basis for the use of quantitative NMB monitoring; (b) offer a set of recommendations for quantitative NMB monitoring standards; (c) specify educational goals; and (d) propose training recommendations to ensure proper neuromuscular monitoring and management. The panel believes that whenever a neuromuscular blocker is administered, neuromuscular function must be monitored by observing the evoked muscular response to peripheral nerve stimulation. Ideally, this should be done at the hand muscles (not the facial muscles) with a quantitative (objective) monitor. Objective monitoring (documentation of train-of-four ratio ≥0.90) is the only method of assuring that satisfactory recovery of neuromuscular function has taken place. The panel also recommends that subjective evaluation of the responses to train-of-four stimulation (when using a peripheral nerve stimulator) or clinical tests of recovery from NMB (such as the 5-second head lift) should be abandoned in favor of objective monitoring. During an interim period for establishing these recommendations, if only a peripheral nerve stimulator is available, its use should be mandatory in any patient receiving a neuromuscular blocking drug. The panel acknowledges that publishing this statement per se will not result in its spontaneous acceptance, adherence to its recommendations, or change in routine practice. Implementation of objective monitoring will likely require professional societies and anesthesia department leadership to champion its use to change anesthesia practitioner behavior.

Background: An unanticipated difficult airway during induction of anesthesia can be a vexing problem. In the setting of can't intubate, can't ventilate (CICV), rapid recovery of spontaneous ventilation is a reasonable goal. The urgency of restoring ventilation is a function of how quickly a patient's hemoglobin oxygen saturation decreases versus how much time is required for the effects of induction drugs to dissipate, namely the duration of unresponsiveness, ventilatory depression, and neuromuscular blockade. It has been suggested that prompt reversal of rocuronium-induced neuromuscular blockade with sugammadex will allow respiratory activity to recover before significant arterial desaturation. Using pharmacologic simulation, we compared the duration of unresponsiveness, ventilatory depression, and neuromuscular blockade in normal, obese, and morbidly obese body sizes in this life-threatening CICV scenario. We hypothesized that although neuromuscular function could be rapidly restored with sugammadex, significant arterial desaturation will occur before the recovery from unresponsiveness and/or central ventilatory depression in obese and morbidly obese body sizes., Methods: We used published models to simulate the duration of unresponsiveness and ventilatory depression using a common induction technique with predicted rates of oxygen desaturation in various size patients and explored to what degree rapid reversal of rocuronium-induced neuromuscular blockade with sugammadex might improve the return of spontaneous ventilation in CICV situations., Results: Our simulations showed that the duration of neuromuscular blockade was longer with 1.0 mg/kg succinylcholine than with 1.2 mg/kg rocuronium followed 3 minutes later by 16 mg/kg sugammadex (10.0 vs 4.5 minutes). Once rocuronium neuromuscular blockade was completely reversed with sugammadex, the duration of hemoglobin oxygen saturation >90%, loss of responsiveness, and intolerable ventilatory depression (a respiratory rate of ≤4 breaths/min) were dependent on the body habitus and duration of oxygen administration. There is a high probability of intolerable ventilatory depression that extends well beyond the time when oxygen saturation decreases <90%, especially in obese and morbidly obese patients. If ventilatory rescue is inadequate, oxygen desaturation will persist in the latter groups, despite full reversal of neuromuscular blockade. Depending on body habitus, the duration of intolerable ventilatory depression after sugammadex reversal may be as long as 15 minutes in 5% of individuals., Conclusions: The clinical management of CICV should focus primarily on restoration of airway patency, oxygenation, and ventilation consistent with the American Society of Anesthesiologist's practice guidelines for management of the difficult airway. Pharmacologic intervention cannot be relied upon to rescue patients in a CICV crisis.

Background: With the use of previously published data, new sevoflurane-remifentanil interaction models of various degrees of sedation were created and adapted to desflurane-fentanyl by using minimal alveolar concentration and opioid equivalencies. These models were used to predict return of responsiveness in patients undergoing scoliosis surgery during a wake-up test. Our hypothesis was that one of the interaction models would accurately predict return of responsiveness during a wake-up test., Methods: Three new sevoflurane-remifentanil interaction models were constructed from previous observations in volunteers by using the Observer's Assessment of Alertness/Sedation (OAA/S) scores. These models included predictions of OAA/S<2 (unresponsive), OAA/S< 3, and OAA/S<4 (sedation). Twenty-three patients scheduled for scoliosis surgery received a fentanyl-desflurane anesthetic. With the use of published pharmacokinetic models, predictions of fentanyl and desflurane effect-site concentrations were recorded throughout surgery and converted to equivalent remifentanil and sevoflurane effect-site concentrations. Data were recorded every 10 seconds from the time when desflurane was turned off until 10 minutes after the patients responded by moving their hands and toes. Model predictions were compared with observations with graphical and temporal analyses., Results: The average difference between the time when a patient first responded and the time when the model predicted that there was a 50% probability that the patient would respond were -2.6 ± 3.6 minutes (mean ± SD) for the OAA/S<2 model, 2.8 ± 5.6 minutes for the OAA/S<3 model and 52.6 ± 32.3 minutes for the OAA/S<4 model., Conclusions: The results confirmed our study hypothesis; a sevoflurane-remifentanil interaction model built from observations in volunteers and adapted to desflurane and fentanyl accurately predicted patient response during a wake-up test. These results were similar to our previous study comparing model predictions and patient observations after a sevoflurane-remifentanil/fentanyl anesthetic. The OAA/S <2 model most accurately predicted the time patients would respond by moving their fingers and toes. This model may help anesthesiologists better predict return of responsiveness during a wake-up test in patients undergoing spine surgery.

Background: Drug administration errors are frequent and are often associated with the misuse of IV infusion pumps. One source of these errors may be the infusion pump's user interface., Methods: We used failure modes-and-effects analyses to identify programming errors and to guide the design of a new syringe pump user interface. We designed the new user interface to clearly show the pump's operating state simultaneously in more than 1 monitoring location. We evaluated anesthesia residents in laboratory and simulated environments on programming accuracy and error detection between the new user interface and the user interface of a commercially available infusion pump., Results: With the new user interface, we observed the number of programming errors reduced by 81%, the number of keystrokes per task reduced from 9.2 ± 5.0 to 7.5 ± 5.5 (mean ± SD), the time required per task reduced from 18.1 ± 14.1 seconds to 10.9 ± 9.5 seconds and significantly less perceived workload. Residents detected 38 of 70 (54%) of the events with the new user interface and 37 of 70 (53%) with the existing user interface, despite no experience with the new user interface and extensive experience with the existing interface., Conclusions: The number of programming errors and workload were reduced partly because it took less time and fewer keystrokes to program the pump when using the new user interface. Despite minimal training, residents quickly identified preexisting infusion pump problems with the new user interface. Intuitive and easy-to-program infusion pump interfaces may reduce drug administration errors and infusion pump-related adverse events.

Background: Remifentanil and propofol are increasingly used for short-duration procedures in spontaneously breathing patients. In this setting, it is preferable to block the response to moderate stimuli while avoiding loss of responsiveness (LOR) and intolerable ventilatory depression (IVD). In this study, we explored selected effects of combinations of remifentanil-propofol effect-site concentrations (Ces) that lead to a loss of response to esophageal instrumentation (EI), LOR, and/or onset of IVD. A secondary aim was to use these observations to create response surface models for each effect measure. We hypothesized that (1) in a large percentage of volunteers, selected remifentanil and propofol Ces would allow EI but avoid LOR and IVD, and (2) the drug interaction for these effects would be synergistic., Methods: Twenty-four volunteers received escalating target-controlled remifentanil and propofol infusions over ranges of 0 to 6.4 ng · mL(-1) and 0 to 4.3 μg · mL(-1), respectively. At each set of target concentrations, responses to insertion of a blunt end bougie into the midesophagus (40 cm), level of responsiveness, and respiratory rate were recorded. From these data, response surface models of loss of response to EI and IVD were built and characterized as synergistic, additive, or antagonistic. A previously published model of LOR was used., Results: Of the possible 384 assessments, volunteers were unresponsive to EI at 105 predicted remifentanil-propofol Ces; in 30 of these, volunteers had no IVD; in 30, volunteers had no LOR; and in 9, volunteers had no IVD or LOR. Many other assessments over the same concentration ranges, however, did have LOR and/or IVD. The combinations that allowed EI and avoided IVD and/or LOR primarily clustered around remifentanil-propofol Ces ranging from 0.8 to 1.6 ng · mL(-1) and 1.5 to 2.7 μg · mL(-1), respectively, and to a lesser extent approximately 3.0 to 4.0 ng · mL(-1) and 0.0 to 1.1 μg · mL(-1), respectively. Models of loss of response to EI and IVD both demonstrated a synergistic interaction between remifentanil and propofol., Conclusion: Selected remifentanil-propofol concentration pairs, especially higher propofol-lower remifentanil concentration pairs, can block the response to EI while avoiding IVD in spontaneously breathing volunteers. It is, however, difficult to block the response to EI and avoid both LOR and IVD. It may be necessary to accept some discomfort and blunt rather than block the response to EI to consistently avoid LOR and IVD.

Introduction: Sevoflurane-remifentanil interaction models that predict responsiveness and response to painful stimuli have been evaluated in patients undergoing elective surgery. Preliminary evaluations of model predictions were found to be consistent with observations in patients anesthetized with sevoflurane, remifentanil, and fentanyl. This study explored the feasibility of adapting the predictions of sevoflurane-remifentanil interaction models to an isoflurane-fentanyl anesthetic. We hypothesized that model predictions adapted for isoflurane and fentanyl are consistent with observed patient responses and are similar to the predictions observed in our previous work with sevoflurane-remifentanil/fentanyl anesthetics., Methods: Twenty-five patients scheduled for elective surgery received a fentanyl-isoflurane anesthetic. Model predictions of unresponsiveness were recorded at emergence, and predictions of a response to noxious stimulus were recorded when patients first required analgesics in the recovery room. Model predictions were compared with observations with graphical and temporal analyses. Results were also compared with our previous predictions after the administration of a sevoflurane-remifentanil/fentanyl anesthetic., Results: Although patients were anesthetized, model predictions indicated a high likelihood that patients would be unresponsive (> or = 99%). After the termination of the anesthetic, model predictions of responsiveness well described the actual fraction of patients observed to be responsive during emergence. Half of the patients woke within 2 min of the 50% model-predicted probability of unresponsiveness; 70% woke within 4 min. Similarly, predictions of a response to a noxious stimulus were consistent with the number of patients who required fentanyl in the recovery room. Model predictions after the administration of an isoflurane-fentanyl anesthetic were similar to model predictions after a sevoflurane-remifentanil/fentanyl anesthetic., Discussion: The results confirmed our study hypothesis; model predictions for unresponsiveness and no response to painful stimuli, adapted to isoflurane-fentanyl were consistent with observations. These results were similar to our previous study comparing model predictions and patient observations after a sevoflurane-remifentanil/fentanyl anesthetic.

Introduction: We previously reported models that characterized the synergistic interaction between remifentanil and sevoflurane in blunting responses to verbal and painful stimuli. This preliminary study evaluated the ability of these models to predict a return of responsiveness during emergence from anesthesia and a response to tibial pressure when patients required analgesics in the recovery room. We hypothesized that model predictions would be consistent with observed responses. We also hypothesized that under non-steady-state conditions, accounting for the lag time between sevoflurane effect-site concentration (Ce) and end-tidal (ET) concentration would improve predictions., Methods: Twenty patients received a sevoflurane, remifentanil, and fentanyl anesthetic. Two model predictions of responsiveness were recorded at emergence: an ET-based and a Ce-based prediction. Similarly, 2 predictions of a response to noxious stimuli were recorded when patients first required analgesics in the recovery room. Model predictions were compared with observations with graphical and temporal analyses., Results: While patients were anesthetized, model predictions indicated a high likelihood that patients would be unresponsive (> or = 99%). However, after termination of the anesthetic, models exhibited a wide range of predictions at emergence (1%-97%). Although wide, the Ce-based predictions of responsiveness were better distributed over a percentage ranking of observations than the ET-based predictions. For the ET-based model, 45% of the patients awoke within 2 min of the 50% model predicted probability of unresponsiveness and 65% awoke within 4 min. For the Ce-based model, 45% of the patients awoke within 1 min of the 50% model predicted probability of unresponsiveness and 85% awoke within 3.2 min. Predictions of a response to a painful stimulus in the recovery room were similar for the Ce- and ET-based models., Discussion: Results confirmed, in part, our study hypothesis; accounting for the lag time between Ce and ET sevoflurane concentrations improved model predictions of responsiveness but had no effect on predicting a response to a noxious stimulus in the recovery room. These models may be useful in predicting events of clinical interest but large-scale evaluations with numerous patients are needed to better characterize model performance.

Introduction: In this study, we explored how a set of remifentanil-propofol response surface interaction models developed from data collected in volunteers would predict responses to events in patients undergoing elective surgery. Our hypotheses were that these models would predict a patient population's loss and return of responsiveness and the presence or absence of a response to laryngoscopy and the response to pain after surgery., Methods: Twenty-one patients were enrolled. Anesthesia consisted of remifentanil and propofol infusions and fentanyl boluses. Loss and return of responsiveness, responses to laryngoscopy, and responses to postoperative pain were assessed in each patient. Model predictions were compared with observed responses., Results: The loss of responsiveness model predicted that patients would become unresponsive 2.4 +/- 2.6 min earlier than observed. At the time of laryngoscopy, the laryngoscopy model predicted an 89% probability of no response to laryngoscopy and 81% did not respond. During emergence, the loss of responsiveness model predicted return of responsiveness 0.6 +/- 5.1 min before responsiveness was observed. The mean probability of no response to pressure algometry was 23% +/- 35% when patients required fentanyl for pain control., Discussion: This preliminary assessment of a series of remifentanil-propofol interaction models demonstrated that these models predicted responses to selected pertinent events during elective surgery. However, significant model error was evident during rapid changes in predicted effect-site propofol-remifentanil concentration pairs.

Introduction: A graphic presentation of complex information can facilitate early detection and management of adverse events. Prior work found that graphical presentation of selected cardiovascular variables led to earlier detection of a simulated ischemic event. Based on these findings, a second evaluation explored the utility of a graphical cardiovascular display (GCD) in a variety of simulated adverse cardiopulmonary events for two different display configurations. In this evaluation, we revised the GCD to present hemodynamic variables with or without a pulmonary artery catheter. Our hypotheses were that the revised GCD would improve detection of adverse cardiopulmonary events and add no additional perceived workload., Methods: Sixteen anesthesiologists and anesthesia residents were enrolled in a simulation-based evaluation of the GCD. Participants were randomly split into two groups balanced for expertise and asked to manage six simulated adverse cardiopulmonary events. The GCD was present in half of the simulations, balanced across scenarios and groups. Participants' verbalizations and actions during each scenario were recorded and transcribed. Transcripts of treatment interventions were subsequently rated by two blinded expert anesthesiologists. Perceived workload, time to detection, and proper treatment of the adverse event were compared between groups., Results: Experts ranked anesthesiologists using the GCD as being more effective overall and individually in three of six scenarios. Use of the GCD was demonstrated to influence the time to detection and the time to treatment of some critical events. There were no workload differences between display groups., Discussion: Treatment intervention by participants using the GCD was rated superior by two blinded experts. The presence of the GCD resulted in a modest improvement in the time to detect myocardial ischemia and increased pulmonary capillary wedge pressure. The GCD may be a useful adjunct to monitor patients during adverse cardiopulmonary events.

Unlabelled: When opioids are used for postoperative pain control, it is useful to define the dose-response relationship for analgesia and respiratory depression. We studied 20 chronically opioid-consuming patients having elective multilevel spine fusion. Preoperatively, each patient received a fentanyl infusion of 2 microg x kg(-1) x min(-1) until the respiratory rate was <5 breaths/min. Pharmacokinetic simulations were used to estimate the effect site concentration at the time of respiratory depression and to predict the patient-controlled analgesia settings that would provide an effect-site fentanyl concentration that was 30% of the concentration associated with respiratory depression. Postoperatively, patient-controlled analgesia settings were adjusted to achieve 2-3 demand doses per hour. At steady-state patient-controlled analgesia settings, arterial blood gases and plasma fentanyl levels were measured. Sixteen patients required no adjustment or one patient-controlled analgesia adjustment. The median arterial Pco(2) level was 41 mm Hg and the interquartile range was 39-46 mm Hg. Plasma fentanyl levels demonstrated a significant correlation to the estimated effect-site concentration associated with respiratory depression determined during the preoperative fentanyl challenge. A preoperative fentanyl challenge used with pharmacokinetic simulations may be a useful tool to individualize the administration of analgesics to chronically opioid-consuming patients., Implications: In chronically opioid-consuming patients, doses causing respiratory depression and analgesia may differ from those in opioid-naive individuals. A preoperative infusion of fentanyl, used in conjunction with pharmacokinetic simulation, may be a valuable tool for identifying clinical end-points, such as respiratory depression and analgesia, and individualizing postoperative treatment of pain in patients who chronically consume opioids.

Unlabelled: We studied the influence of hemorrhagic shock on the pharmacology of etomidate in swine. Sixteen swine were randomly assigned to control and shock groups. The shock group was bled to a mean arterial blood pressure of 50 mm Hg and held there until 30 mL/kg blood was removed. Etomidate 300 micro g x kg(-1) x min(-1) was infused for 10 min to both groups. Fifteen arterial samples were collected until 180 min after the infusion began to determine drug concentration. Pharmacokinetic variables for each group were estimated by using a three-compartment model. The bispectral index scale was used as a measure of drug effect. The pharmacodynamics were characterized by using a sigmoid inhibitory maximal effect model. The raw data revealed a 25% increase in the plasma etomidate concentration at the end of the 10-min infusion which resolved after termination of the infusion in the shock group. The pharmacokinetic analysis revealed subtle changes in the variable estimates between groups. The etomidate infusion produced a similar Bispectral Index Scale change in both groups. These results demonstrated that, unlike the influence of hemorrhagic shock on other sedative hypnotics and opioids, moderate hemorrhagic shock produced minimal changes in the pharmacokinetics and no change in the pharmacodynamics of etomidate., Implications: Hemorrhagic shock produced minimal changes in the pharmacokinetics and no change in the pharmacodynamics of etomidate in swine. These results suggest that, unlike other sedative hypnotics and opioids, minimal adjustment in the dose of etomidate is required to achieve the same drug effect during hemorrhagic shock.

Implications: The pharmacokinetic characteristics of midazolam and remifentanil administered by bolus injection may make them advantageous for providing brief, intense analgesia without prolonged respiratory depression. This application is particularly useful for awake, direct laryngoscopy.