Temperature-resilient solid-state organic artificial synapses for neuromorphic computing.

Devices with tunable resistance are highly sought after for neuromorphic computing. Conventional resistive memories, however, suffer from nonlinear and asymmetric resistance tuning and excessive write noise, degrading artificial neural network (ANN) accelerator performance. Emerging electrochemical random-access memories (ECRAMs) display write linearity, which enables substantially faster ANN training by array programing in parallel. However, state-of-the-art ECRAMs have not yet demonstrated stable and efficient operation at temperatures required for packaged electronic devices (~90°C). Here, we show that (semi)conducting polymers combined with ion gel electrolyte films enable solid-state ECRAMs with stable and nearly temperature-independent operation up to 90°C. These ECRAMs show linear resistance tuning over a >2× dynamic range, 20-nanosecond switching, submicrosecond write-read cycling, low noise, and low-voltage (±1 volt) and low-energy (~80 femtojoules per write) operation combined with excellent endurance (>109 write-read operations at 90°C). Demonstration of these high-performance ECRAMs is a fundamental step toward their implementation in hardware ANNs.

Succinylcholine-induced hyperkalemia in a patient with mucositis secondary to chemotherapy.

OBJECTIVE: To report a case of fatal hyperkalemia owing to succinylcholine administration in a patient with mucositis secondary to chemotherapy. DESIGN: Case report. SETTING: Adult intensive care unit (ICU) at Dartmouth-Hitchcock Medical Center. PATIENTS: One patient with mucositis secondary to chemotherapy. MEASUREMENTS AND MAIN RESULTS: A 37-yr-old female with recently diagnosed acute myelogenous leukemia was admitted to the ICU with mental status changes and progressive dyspnea requiring intubation and mechanical ventilation. Before ICU admission, the patient had suffered from painful mucositis causing severe dysphagia and bleeding, which was thought to be the result of chemotherapy. By the 10th ICU day, the patient's respiratory and mental status improved and the patient was successfully extubated. However, 8 hrs after extubation, she gradually developed severe respiratory distress, requiring reintubation and mechanical ventilation. The patient was given 14 mg of etomidate and 100 mg of succinylcholine intravenously. Immediately after the intubation, she suffered cardiac arrest. Her serum potassium level was 13.1 mEq/L and HCO3- was 16 mEq/L. The resuscitation attempt was unsuccessful, and the patient was pronounced dead. CONCLUSION: Oral mucositis is a frequent and potentially severe complication of cancer chemotherapy. We believe that mucositis was a contributing factor to this case of fatal hyperkalemia after administration of succinylcholine, with a mechanism similar to that reported with thermal injury. Only nondepolarizing muscle relaxants should be used in patients who are at risk for mucositis. Mucositis should be added to the list of conditions in which succinylcholine is contraindicated.

A comparison of mivacurium dosage requirements during isoflurane and desflurane anesthesia.

STUDY OBJECTIVE: To evaluate the dose requirement and recovery characteristics of mivacurium infusions during anesthesia with equipotent concentrations of either desflurane or isoflurane. DESIGN: Randomized, open-study comparing the effects of desflurane and isoflurane on mivacurium-induced neuromuscular blockade. SETTING: Operating suite of a university-affiliated medical center. PATIENTS: 41 ASA status I, II, and III adult patients, requiring more than 45 minutes of neuromuscular blockade for surgery. INTERVENTIONS: Following a standardized induction sequence and established steady desflurane-nitrous oxide (DES group) or isoflurane-nitrous oxide (ISO group) anesthesia at 1 minimum alveolar concentration (MAC), an intubating dose of 0.2 mg/kg of mivacurium chloride was administered. Ventilation was maintained with a face mask until the first twitch (T1) of the evoked train-of-four (TOF) reached 10% or less of control when tracheal intubation was performed. T1 was allowed to return to 10% of its control value. An infusion of mivacurium at the initial rate of 5 micrograms/kg/min was then started and adjusted to maintain T1 at 10% +/- 2% of control. Within 20 minutes of completion of surgery, the mivacurium infusion was stopped, and the time for the evoked electromyograph (EMG) to return to 25% and 75% of the original baseline was noted. MEASUREMENTS AND MAIN RESULTS: Neuromuscular function was monitored continuously by an evoked EMG. The average infusion rate was 5.7 +/- 2.4 micrograms/kg/min (mean +/- SD) for DES group (n = 20) and 6.6 +/- 2.7 micrograms/kg/min for ISO group (n = 21) (p = NS). There was no change in the infusion rate of mivacurium over time for both groups. However, there was an inverse relationship in both groups between the time to recovery following a bolus dose and the subsequent mean infusion rate of mivacurium (correlation coefficient = -5.0; p < 0.005). The spontaneous recovery index (T25-75) for the two groups was identical, 11.5 +/- 4.9 min (mean +/- SD) for DES group and 11.5 +/- 7.9 min for ISO group (p = NS). CONCLUSION: There were no differences in the dose requirement and recovery indices of mivacurium during either desflurane or isoflurane-based anesthesia. Patients who took longer to recover from the bolus dose in both groups showed a subsequent reduction in dose requirements of mivacurium.

Preliminary pharmacokinetics and pharmacodynamics of an ultra-short-acting opioid: remifentanil (GI87084B).

Remifentanil is a newly synthesized 4-anilido-piperidine with an ester side chain susceptible to esterase metabolism. We evaluated the safety, analgesic efficacy, and pharmacokinetics of remifentanil in 48 male volunteers. Volunteers were randomized to receive increasing doses of remifentanil, alfentanil, or placebo. Analgesic efficacy was evaluated by increasing tolerance to a spring-loaded rod measured at the tibia and sternum at multiple time points. Respiratory depression was measured by changes in arterial blood gas tensions and peripheral hemoglobin oxygen saturation. Hemodynamics were continuously monitored by means of an intra-arterial catheter. Both remifentanil and alfentanil produced a dose-dependent increase in analgesia and respiratory depression. Remifentanil was 20 to 30 times more potent (milligram to milligram) than alfentanil when assessed by either analgesic efficacy or respiratory measures. The pharmacokinetics of remifentanil were best described by a biexponential decay curve. Remifentanil had a small volume of distribution of 0.39 (SD, +/- 0.25) L/kg (alfentanil, 0.52 +/- 2 L/kg), with a rapid distribution phase of 0.94 (SD, +/- 0.57) min and an extremely short elimination half-life of 9.5 (SD, +/- 4) min compared with an elimination half-life of alfentanil of 58 (SD, +/- 7.6) min. The t1/2 ke0 (half-time for equilibration between plasma and the effect compartment) of remifentanil for analgesia was calculated as 1.3 min. Thus, remifentanil appears to have a pharmacologic profile similar to other potent mu agonists, but with exceptionally short-lasting pharmacokinetics, which is likely to make it a very useful opioid for clinical practice.

Accuracy of drug infusion pumps under computer control.

Prototype systems implementing algorithms for automated drug infusions are typically constructed by coupling a microcomputer to a drug infusion pump through a serial communications interface. Infusion rates demanded of the infusion pump in many computed-controlled drug delivery applications are made to change at intervals much shorter than those encountered under routine clinical use. Because the ability of infusion pumps to maintain accurate flow rates during high frequency rate changes has not been documented, the purpose of this study was to validate the volumetric accuracy of three commercially available infusion pumps operating in a demanding computer-controlled application. In independent 2-h evaluations, the infusion rate demanded of each pump changed as often as every 5, 10, or 15 s using an algorithm for computer-controlled pharmacokinetic model-driven intravenous infusion. Accuracy of the infusion devices was determined gravimetrically. At all measurement times, each of the infusion pumps was accurate to within approximately +/- 5% of the expected volumetric output under each of the infusion rate intervals tested. Flow rate accuracy of +/- 5% is equal to the nominal expected accuracy of these infusion pumps in conventional clinical use.

Validation of 133Xe clearance as a cerebral blood flow measurement technique during cardiopulmonary bypass.

133Xe clearance to measure cerebral blood flow (CBF) was examined in 10 dogs during cardiopulmonary bypass. As a reference method, a continuous Kety-Schmidt technique (CBFKS) with 133Xe as indicator was used. Extracranial tissue was removed to directly place the 133Xe detectors on the skull, and the head was covered with a 3 mm lead shield to minimize contamination of the 133Xe clearance curve with extracranial radiation. 133Xe detectors for the Kety-Schmidt technique were embedded in a shielded brass block to minimize interference with radiation from the animal's body. 133Xe clearance data were analyzed using stochastic (CBF10, CBF15, and CBFINF) and initial slope methods (CBFIS), and the results were compared with CBFKS using linear regression. CBF15 and CBFINF yielded similar CBF values as CBFKS (CBFKS = 0.97.CBF15-2.08, r = 0.92, p less than 0.01; CBFKS = 1.13.CBFINF-1.21, r = 0.92, p less than 0.01). CBF10 slightly overestimated CBFKS but still showed a close correlation to CBFKS (CBFKS = 0.89.CBF10-2.58, r = 0.92, p less than 0.01) and CBFIS considerably overestimated CBFKS (CBFKS = 0.60.CBFIS-1.27, r = 0.87, p less than 0.01). With extracranial contamination of the 133Xe clearance curve minimized, all 133Xe clearance techniques used to measure CBF were consistently related to CBFKS in a constant, significant manner. 133Xe clearance therefore is a valid method to assess CBF during cardiopulmonary bypass.

Cerebral blood flow response to changes in arterial carbon dioxide tension during hypothermic cardiopulmonary bypass in children.

We examined the relationship of changes in partial pressure of carbon dioxide on cerebral blood flow responsiveness in 20 pediatric patients undergoing hypothermic cardiopulmonary bypass. Cerebral blood flow was measured during steady-state hypothermic cardiopulmonary bypass with the use of xenon 133 clearance methodology at two different arterial carbon dioxide tensions. During these measurements there was no significant change in mean arterial pressure, nasopharyngeal temperature, pump flow rate, or hematocrit value. Cerebral blood flow was found to be significantly greater at higher arterial carbon dioxide tensions (p less than 0.01), so that for every millimeter of mercury rise in arterial carbon dioxide tension there was a 1.2 ml.100 gm-1.min-1 increase in cerebral blood flow. Two factors, deep hypothermia (18 degrees to 22 degrees C) and reduced age (less than 1 year), diminished the effect carbon dioxide had on cerebral blood flow responsiveness but did not eliminate it. We conclude that cerebral blood flow remains responsive to changes in arterial carbon dioxide tension during hypothermic cardiopulmonary bypass in infants and children; that is, increasing arterial carbon dioxide tension will independently increase cerebral blood flow.

Clinical responses to ORG 9426 during isoflurane anesthesia.

To determine average dose requirements and pharmacodynamic characteristics before general clinical use, the dose-response curve, onset time, and recovery time for the neuromuscular relaxant ORG 9426 were determined in 72 adult patients given doses of 120, 160, 200, or 240 micrograms/kg after establishment of a steady-state expired isoflurane concentration of approximately 1%. Neuromuscular blockade was continuously recorded using the ulnar evoked electromyogram. Using the log probit method, ED95 was 268 micrograms/kg, ED90 was 251 micrograms/kg, and ED50 was 144 micrograms/kg. The time until 80% blockade was 1.9 min at 240 micrograms/kg, and the average time to peak effect was 4.6 min, which did not vary with dose. The clinical duration (injection until T1 returned to 25%) was 20.5 min, and the recovery index (T1 increased from 25% to 75% of control) was 15.4 min, after a total dose of 300 micrograms/kg. The duration of 75-micrograms/kg and 100-micrograms/kg repeat (maintenance) dose was 14.6 and 17.8 min, respectively, and no cumulative effect was apparent after as many as five maintenance doses. No cardiovascular side effects were seen at doses used in the study. We conclude that ORG 9426 is a nondepolarizing muscle relaxant with a rapid onset and short duration of action that deserves further clinical evaluation.

The relative accuracies of two automated noninvasive arterial pressure measurement devices.

We compared the accuracies of two types of noninvasive blood pressure devices. Thirty-two patients requiring an intraarterial catheter for anesthetic management underwent simultaneous monitoring with Dinamap 1846SX and Ohmeda Finapres 3700 devices. For the first 10 minutes of recording, new Dinamap determinations were performed every 60 seconds; subsequent recordings were made at 3-minute intervals. Data were obtained at the time of new Dinamap readings, and twice between new readings to approximate the real-time performance of the two monitors. We defined superior accuracy as a statistically significant difference in mean absolute error greater than 5 mm Hg. With these criteria, pooled data from all patients revealed no difference in performance, even in real time. Pooled data can be misleading since there was a significant amount of variation in accuracy for both monitors. Therefore, we used nonparametric analysis to determine how many individual patients were monitored better by either device. When we compared only data from new Dinamap readings, the Finapres monitor showed superior performance for systolic readings in 13 patients, versus 6 patients for the Dinamap (P less than 0.05, chi-square test). Similar analysis for diastolic and mean pressure performance did not reach statistical significance. However, in real time, the Finapres unit monitored more patients more accurately for systolic (14 Finapres versus 3 Dinamap), diastolic (11 Finapres versus 3 Dinamap), and mean (10 Finapres versus 3 Dinamap) pressure determinations. The magnitude of these differences were, however, less dramatic than expected. This was probably due to stabilization of arterial pressure during the anesthetic, which minimized the error due to intermittent sampling. We conclude that continuous Finapres readings and new Dinamap determinations are equally accurate for diastolic and mean arterial pressures. The accuracy of Finapres appears to be slightly superior for systolic pressure. The intermittent sampling of oscillometric devices compromises their performance relative to the Finapres in many, but not all, cases.

Pharmacokinetic model-driven infusion of fentanyl: assessment of accuracy.

Computer-assisted continuous infusion (CACI) is a pharmacokinetic model-driven infusion device that enables physicians to administer intravenous (iv) drugs in a quantitative fashion, specifying a theoretical blood or plasma concentration. This study evaluated the accuracy of CACI administration of fentanyl using a newly developed CACI device programmed with a well-known set of pharmacokinetic parameters for fentanyl. Patients received diazepam 1 or 2 h before surgery. Anesthesia was induced by a combination of 70% N2O and fentanyl administered by CACI to a predicted concentration of 15-25 ng.ml-1. After neuromuscular blockade and tracheal intubation, the desired plasma fentanyl concentration (setpoint) entered into CACI was 3-6 ng.ml-1, and then the setpoint fentanyl concentration was titrated according to strict criteria of adequate or inadequate anesthesia. Plasma samples for subsequent assay of fentanyl concentration then were taken: at predefined stimuli, when inadequate anesthesia occurred, or 5 min before an anticipated decrease in the fentanyl setpoint. The predictive accuracy of CACI was assessed by calculating for each patient the tenth, 50th, and 90th percentile of the performance error and absolute performance error from each measured and predicted plasma sample pair. Cumulative probability functions for each of these were then plotted. Precision was defined as the dispersion of the tenth to 90th percentile of the median percent performance error for the population and was found to be -31-26%. The median population performance error was -4%, and the median population absolute performance error was 21%.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetic patients have abnormal cerebral autoregulation during cardiopulmonary bypass.

We tested the hypothesis that insulin-dependent diabetic patients with coronary artery bypass graft surgery experience altered coupling of cerebral blood flow and oxygen consumption. In a study of 23 patients (11 diabetics and 12 age-matched controls), cerebral blood flow was measured using 133Xe clearance during nonpulsatile, alpha-stat blood gas managed cardiopulmonary bypass at the conditions of hypothermia and normothermia. In diabetic patients, the cerebral blood flow at 26.6 +/- 2.42 degrees C was 25.3 +/- 14.34 ml/100 g/min and at 36.9 +/- 0.58 degrees C it was 27.3 +/- 7.40 ml/100 g/min (p = NS). The control patients increased cerebral blood flow from 20.7 +/- 6.78 ml/100 g/min at 28.4 +/- 2.81 degrees C to 37.6 +/- 8.81 ml/100 g/min at 36.5 +/- 0.45 degrees C (p less than or equal to 0.005). The oxygen consumption was calculated from jugular bulb effluent and increased from hypothermic values of 0.52 +/- 0.20 ml/100 g/min in diabetics to 1.26 +/- 0.28 ml/100 g/min (p = 0.001) at normothermia and rose from 0.60 +/- 0.27 to 1.49 +/- 0.35 ml/100 g/min (p = 0.0005) in the controls. Thus, despite temperature-mediated changes in oxygen consumption, diabetic patients did not increase cerebral blood flow as metabolism increased. Arteriovenous oxygen saturation gradients and oxygen extraction across the brain were calculated from arterial and jugular bulb blood samples. The increase in arteriovenous oxygen difference between temperature conditions in diabetic patients and controls was significantly different (p = 0.01). These data reveal that diabetic patients lose cerebral autoregulation during cardiopulmonary bypass and compensate for an imbalance in adequate oxygen delivery by increasing oxygen extraction.

The accuracy of rapid oscillometric blood pressure determination.

The Dinamap 1846SX (DIN) offers a "stat mode" (SM) for rapid repetitive blood pressure determinations, but its accuracy has not been reported. Thirty patients who required an intra-arterial catheter (IAC) for management of anesthesia underwent induction with concomitant noninvasive blood pressure measurement provided by a DIN set in SM. Computerized automated data acquisition recorded digital outputs from both monitors at the time of new SM readings. Systolic pressure mean absolute error (MAE) was 13.3 +/- 5.7 mmHg (mean +/- SEM) and the mean error (bias) was -8.7 +/- 9.8 mmHg. Mean pressure MAE was 6.8 +/- 3.4 mmHg and bias was -0.5 +/- 6.3 mmHg. Diastolic pressure MAE was 7.0 +/- 3.3 mmHg and bias was -0.3 +/- 6.5 mmHg. There was a tendency for systolic pressure readings to underestimate IAC pressures at higher pressures. These findings echo results reported previously for DIN operating in its normal mode. Rapid arterial pressure determination by SM does not appear to compromise accuracy.

Continuous infusion of alfentanil for maintenance of anesthesia: comparison with halothane anesthesia.

This study compares anesthetic maintenance, hemodynamic stability, and speed of recovery obtained with inhalational halothane versus intravenous alfentanil anesthesia administered continuously. In two groups of patients, anesthesia was induced with sodium thiopental, maintained with 70% nitrous oxide in 30% oxygen, and either halothane (n = 10) or a continuous infusion of alfentanil (n = 10). The administration of the allocated anesthetic was adjusted according to strict predefined criteria of inadequate anesthesia. After endotracheal intubation, hemodynamics (heart rate, systolic and diastolic pressure) changed less in the alfentanil group (P less than .01). Overall hemodynamic stability was the same in both groups. In neither group was there recall of intraoperative events. Recovery was assessed by the time from cessation of nitrous oxide administration to return of spontaneous ventilation, response to simple command, extubation, orientation, and discharge from the recovery area. The time taken to respond to simple command was significantly shorter in the alfentanil group (P less than .05), but other indices of recovery were similar.

A comparison of vecuronium by continuous infusion with either isoflurane or fentanyl-nitrous oxide anesthesia.

The average infusion rate and efficacy of vecuronium bromide continuous infusions for surgical relaxation in human subjects was evaluated. Nineteen adult patients requiring more than 120 min of neuromuscular blockade for surgery were randomized to receive either fentanyl-nitrous oxide (Group 1) or isoflurane-fentanyl-nitrous oxide (Group 2). Neuromuscular function was monitored using train-of-four evoked electromyography (EMG). Following an intubating dose of 0.08 mg/kg of vecuronium bromide, the first twitch was allowed to return to 10% of its control value. An infusion of vecuronium at an initial rate of 60.0 micrograms/kg/h was then started and adjusted to maintain the first twitch at 10% of control. The average infusion rate (total infusion dose divided by the duration of the infusion) was 57.2 +/- 14 micrograms/kg/h in Group 1 (n = 10) and 42.4 +/- 12 micrograms/kg/h (n = 9) in Group 2, approximately 25% less (p = 0.02). There was a significant decrease in the infusion rate with time in Group 1 (p = 0.02), but this decrease was not observed in Group 2.