P. Amorim

The importance of sodium for anoxic transmission damage in rat hippocampal slices: mechanisms of protection by lidocaine.

1. The effect of sodium influx on anoxic damage was investigated in rat hippocampal slices. Previous experiments demonstrated that a concentration of tetrodotoxin which blocks neuronal transmission protects against anoxic damage. In this study we examined low concentrations of lidocaine (lignocaine; which do not block neuronal transmission), for their effect on recovery of the evoked population spike recorded from the CA1 pyramidal cell layer. 2. Recovery of the population spike, measured 60 min after a 5 min anoxic period, was 4 +/‐ 2% of its preanoxic, predrug level. Lidocaine concentrations of 10, 50, and 100 microM significantly improved recovery to 56 +/‐ 12, 80 +/‐ 7 and 70 +/‐ 14%, respectively. 3. Lidocaine (10 microM) did not alter the size of the evoked response before anoxia and had no significant effect on potassium levels or calcium influx during anoxia. It did, however, reduce cellular sodium levels (146 +/‐ 7 vs. 202 +/‐ 12 nmol mg‐1) and preserve ATP levels (2.17 +/‐ 0.07 vs. 1.78 +/‐ 0.07 nmol mg‐1) during anoxia. All values were measured at the end of 5 min of anoxia except those for Ca2+ influx which were measured during 10 min of anoxia. 4. High concentrations of lidocaine (100 microM) did not improve recovery significantly over that observed with 10 microM. They also had no significantly greater effects on sodium levels than 10 microM lidocaine (137 +/‐ 12 vs. 146 +/‐ 7 nmol mg‐1); however, 100 microM lidocaine significantly improved potassium (202 +/‐ 18 vs. 145 +/‐ 6 nmol mg‐1) and ATP (2.57 +/‐ 0.06 vs. 2.17 +/‐ 0.07 nmol mg‐1) levels, while reducing calcium influx (7.76 +/‐ 0.12 vs. 9.24 +/‐ 0.39 nmol mg‐1 (10 min)‐1) when compared with 10 microM lidocaine. 5. We conclude that sodium influx and ATP depletion are of major importance in anoxic damage since 10 microM lidocaine reduced these changes during anoxia and improved recovery of the population spike. In addition, our results indicate that the properties of the sodium channel are altered during anoxia, since sodium influx is blocked by a concentration of lidocaine that does not affect the population spike in the preanoxic period.

Propofol reduces neuronal transmission damage and attenuates the changes in calcium, potassium, and sodium during hyperthermic anoxia in the rat hippocampal slice

Background Propofol reduces cerebral blood flow, cerebral metabolic rate for oxygen, and intracranial pressure and is being increasingly used in neuroanesthesia. In vivo studies have yielded conflicting results on its ability to protect against ischemic brain damage. In the current study, an in vitro model was used to examine the mechanism of propofols action on anoxic neuronal transmission damage.

Effect of small changes in temperature on CA1 pyramidal cells from rat hippocampal slices during hypoxia: implications about the mechanism of hypothermic protection against neuronal damage

Small reductions in temperature have been shown to improve neurologic recovery after ischemia. We have examined the effect of temperature on biochemical and physiological changes during hypoxia using rat hippocampal slices as a model system. The postsynaptic population spike recorded from the CA1 pyramidal cell region of slices subjected to 7 min of hypoxia with hypothermia (34 degrees C) recovered to 73% of its prehypoxic level; slices subjected to the same period of hypoxia at 37 degrees C did not recover. After 7 min of hypoxia ATP fell to 48% of its prehypoxic concentration at 34 degrees C and 30% at 37 degrees C. Potassium fell to 86% during 7 min of hypoxia with hypothermia, this compares to a fall to 58% at 37 degrees C. The increase in sodium after 7 min of hypoxia was also attenuated by hypothermia (133% vs. 163% of its prehypoxic concentration). When the hypoxic period was shortened to 3 min (37 degrees C) the population spike recovered to 94%. If the temperature was increased to 40 degrees C there was only 7% recovery of the population spike after 3 min of hypoxia. With hyperthermia (40 degrees C), ATP fell to 33% after 3 min of hypoxia, this compares to 81% at normothermia. Potassium fell to 76% after 3 min of hypoxia with hyperthermia, this compares to 91% at 37 degrees C. Sodium concentrations increased with hyperthermia before hypoxia, at 3 min of hypoxia there was no significant difference between the hyperthermic and normothermic tissue; there was a large increase in sodium with hyperthermia after 5 min of hypoxia (209% vs. 146%). We conclude that the improved recovery after hypothermic hypoxia is at least in part due to the attenuated changes in ATP, potassium and sodium during hypoxia and that the worsened recovery with hyperthermia is due to an exacerbation of the change in ATP, potassium and sodium concentrations during hypoxia.

The effect of a remifentanil bolus on the bispectral index of the EEG (BIS) in anaesthetized patients independently from intubation and surgical stimuli.

Background and objective: Remifentanil boluses are used in different clinical situations and the effects on bispectral index monitoring are unclear. We analysed the effect of a remifentanil bolus on the bispectral index of the electroencephalogram (bispectral index) under total intravenous anaesthesia with propofol and remifentanil. Methods: ASA I–III patients were included in this study. All patients received a 2 μg k g−1 remifentanil bolus in a period free from stimuli. Bispectral index and haemodynamic data were collected from an A‐2000XP bispectral index monitor (every second) and an AS/3 Datex monitor (every 5 s). Bispectral index data were analysed using the area under the curve. Mean arterial pressure and heart rate were averaged at each 30‐s period and analysed using analysis of variance. Results: A total of 240 bispectral index values were obtained per patient. The area under the curve between 90 and 120 s after the bolus was significantly lower than the basal area under the curve (average of all areas before the bolus, P < 0.05). Mean arterial pressure and heart rate were significantly reduced from 96.4 ± 19.9 mmHg at the time of the bolus to 74.2 ± 16.6 mmHg 120 s after, and from 70 ± 16.4 bpm at the time of the bolus to 61 ± 13.6 bpm after (P < 0.001), respectively. Conclusions: There was a significant reduction in the areas under the curve between 90–120 s following the bolus. Heart rate and blood pressure also showed significant reductions. Thus, remifentanil bolus given under total intravenous anaesthesia with propofol and remifentanil decreases bispectral index, an effect independent of intubation and surgical stimuli.

The effect of isoflurane on biochemical changes during and electrophysiological recovery after anoxia in rat hippocampal slices.

It is unclear whether isoflurane protects against neuronal damage. This study examines the extent and mechanism by which isoflurane might affect anoxic neuronal damage. The size of the evoked postsynaptic population spike recorded from the CA 1 pyramidal cell layer of the rat hippocampal slice 60 min after anoxia was compared with its preanoxic, preisoflurane level. Intracellular adenosine triphosphate (ATP), sodium, and potassium levels were measured in the dentate and CA 1 regions at the end of the anoxic period in similarly treated slices. Isoflurane increased the latency and reduced the amplitude of the evoked response before anoxia. Isoflurane (2%) did not significantly improve recovery of the evoked response after 5 min of anoxia (untreated slices = 6 +/- 2% (mean +/- SEM), isoflurane = 17 +/- 7%); 1.5% isoflurane also did not significantly improve recovery after 4 min of anoxia (untreated = 30 +/- 8% vs. 1.5% isoflurane = 47 +/- 12%). Isoflurane did not significantly attenuate the decrease in ATP levels in either the dentate or CA 1 regions of the hippocampal slice during 4 or 7 min of anoxia; however, there was a significant improvement in ATP levels after 10 min of anoxia in both regions of isoflurane-treated preparations (1.0 +/- 0.1 vs. 1.4 +/- 0.1, CA 1; 1.3 +/- 0.1 vs. 2.0 +/- 0.2 nM/mg dry weight, dentate). Sodium concentrations increased and potassium concentrations decreased during anoxia. Isoflurane did not significantly attenuate the changes in these ions during anoxia. In conclusion, isoflurane does not significantly improve recovery of CA 1 pyramidal cells during anoxia nor does it attenuate the anoxic changes in ATP, sodium, and potassium after 4 or 7 min of anoxia. With a more prolonged period of anoxia (10 min) isoflurane reduces the decrease in ATP levels.

Nitrous oxide impairs electrophysiologic recovery after severe hypoxia in rat hippocampal slices

Background Research has suggested that nitrous oxide may be harmful to ischemic neurons; however, the evidence for this is equivocal. The authors used rat hippocampal slices to examine the effects of nitrous oxide on neuronal hypoxic damage. Methods The evoked population spike (PS) was recorded from hippocampal CA1 pyramidal cells before, during, and after hypoxia. Control groups received nitrogen concentrations equal to nitrous oxide throughout the experiments. Biochemical measurements were made from dissected CA1 regions under experimental conditions that matched the electro-physiology studies. Results Recovery of the PS after hypoxia was 18 +/- 7% in slices treated with 50% nitrous oxide before and during 3.5 min of hypoxia; this compares with 41 +/- 9% (P < 0.05) in nitrogen-treated slices. Slices treated with nitrous oxide (95%) only during hypoxia (6 min) also demonstrated significantly less recovery of the PS than did slices treated with nitrogen. There was no significant difference in recovery if nitrous oxide was discontinued after the hypoxic period. Adenosine triphosphate concentrations after 3.5 min of hypoxia in slices treated with nitrous oxide decreased to the same extent as in nitrogen-treated slices (47% vs. 50%). Calcium influx increased during 10 min of hypoxia in untreated slices, but nitrous oxide did not significantly increase calcium influx during hypoxia. The sodium concentrations increased and potassium concentrations decreased during hypoxia; nitrous oxide did not significantly alter these changes. Conclusions Nitrous oxide impaired electrophysiologic recovery of hippocampal slices after severe hypoxia. Nitrous oxide did not cause significant changes in the biochemical parameters examined.

Clinical variables related to propofol effect-site concentrations at recovery of consciousness after neurosurgical procedures.

Target controlled infusion (TCI) systems and computer data acquisition software are increasingly used in anesthesia. It was hypothesized that the use of such systems might allow retrieval of information useful to anticipate the effect-site concentrations of propofol at which patients would recover from anesthesia. The goal of the study was to identify variables related to propofol effect-site concentrations at recovery of consciousness (ROC). Sixteen patients with a Glasgow of 15, ASA 1 or 2, subjected to neurosurgical procedures, received TIVA with TCI propofol and remifentanil. Data were collected every 5 seconds from Datex AS3 and Aspect A200XP (BIS). Effect-site TCI was used for propofol (initial effect target 5.0 μg/ml) and for remifentanil (initial plasma target 2.5 ng/ml). All clinical events were noted. Variables possibly related to propofol effect-site concentration at ROC were selected. Data are expressed as mean ± SD. Effect-site propofol concentration at ROC was 1.3 ± 0.5 μg/ml. A positive correlation was found between propofol effect-site concentration at ROC and: age (49.3 ± 17 years) (P = 0.003); mean remifentanil dose during surgery (0.11 ± 0.05 μg/kg/min) (P = 0.003); mean propofol dose during surgery (0.12 ± 0.03 mg/kg/min) (P = 0.046); and remifentanil effect-site concentration at ROC (2.85 ± 2.06 ng/ml) (P = 0.002). Propofol effect-site concentrations were not correlated with: weight, height, LBM, duration of anesthesia, minimum BIS at induction (30.4 ± 6.8), time till minimum BIS (4.7 ± 2.2 min), mean and median BIS during surgery (38.2 ± 4.5 and 37.8 ± 5.3). BIS-related variables were not useful as ROC predictors. Only drug variables and age correlated with propofol effect-site concentrations at ROC.

Anoxia reduces depolarization induced calcium uptake in the rat hippocampal slice

Veratridine-induced depolarization caused a large increase in Ca uptake in the rat hippocampal slice (30.2 vs. 9.0 nM/mg dry weight). This uptake was reduced to 18.4 nM/mg when veratridine was combined with anoxia. When compared with veratridine exposure alone, the combination of anoxia and veratridine increased intracellular Na (460 vs. 380 microM/g), decreased intracellular K (30 vs. 40 microM/g) and decreased ATP levels (0.1 vs. 0.8 nM/mg). The changes in Na, K, and ATP should enhance net Ca uptake, yet Ca uptake was reduced. This suggests an effect of anoxia to block Ca channels. In summary anoxia attenuates depolarization-induced Ca uptake. This may represent a mechanism by which neurons are partially protected against anoxic damage which could be more severe if depolarization-induced Ca uptake was not limited.

Synchronization Software for Automation in Anesthesia

This work presents the development of a software for data acquisition and control (ASYS) on a clinical setup. Similar to the industrial Supervisory Control And Data Acquisition (SCADA) the software assembles a target controlled infusion (TCI) monitoring and supervisory control data in real time from devices in a surgical room. The software is not a full controller since the TCI systems comprehend permanent interaction from the anesthesiologist. Based on pharmacokinetic models, the effect-site and plasma concentrations can be related with the drug dose infused and vice versa. The software determines the infusion rates of the drug which are given as commands to the infusion pumps. This software provides the anesthesiologist with a trustworthy tool for managing a safe and balanced anesthesia. Since it also incorporates the acquisition and display of patients brain signals.

Neostigmine vs. sugammadex: observational cohort study comparing the quality of recovery using the Postoperative Quality Recovery Scale

Quality of postoperative recovery is an important outcome after surgery. An observational cohort study was designed to assess the quality of postoperative recovery using the Portuguese version of the Postoperative Quality Recovery Scale (PQRS) in patients treated with neostigmine vs. sugammadex as neuromuscular blocking reversal agents.