bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Spinal Morphine after Long-term Potentiation of Wide Dynamic Range Neurones in the Rat
Authors: Rygh Lars Jørgen , Green Mark , Athauda Nuwan , Tjølsen Arne , Dickenson Anthony H.
Published: November 2003

Background

Studies have shown that long-term increase in the excitability of single wide dynamic range neurones in the spinal dorsal horn of rats may be induced after tetanic stimulation to the sciatic nerve. This sensory event is possibly an in vivo counterpart of long-term potentiation, described in the brain. This study investigated whether this phenomenon occurs in the halothane-anesthetized rat and whether the antinociceptive effects of spinally administered morphine are altered when tested on the enhanced activity.

Methods

Single unit extracellular recordings were made in three different groups of halothane-anesthetized rats (n = 6 in each group). In group 1, the evoked neuronal responses of wide dynamic range neurones by a single electrical stimulus to the peripheral nerve were recorded every 4 min, for 1 h before (baseline) and for 3 h after brief high-frequency conditioning stimulation of the sciatic nerve. In group 2, morphine was applied onto the spinal cord after long-term potentiation had been established. Increasing concentrations of morphine were added until the C fiber-evoked responses were abolished; this was followed by naloxone reversal. In group 3, the same protocol as in group 2 was used except a waiting period substituted for the electrical conditioning.

Results

The C fiber-evoked responses were significantly increased (P < 0.001) after conditioning compared with baseline and those in control animals. Further, significantly higher concentrations of morphine (P = 0.008) were needed to abolish the C fiber-evoked responses in tetanized animals than in control animals. Naloxone reversed the effects of morphine to the predrug potentiated baseline in group 2, showing that opioids do not block the maintenance of spinal long-term potentiation.

Conclusions

Long-term potentiation of C fiber-evoked responses also can be induced in halothane-anesthetized rats, and morphine seems to have less potency during such conditions. These data suggest that long-term potentiation-like mechanisms may underlie some forms of hyperalgesia associated with a reduced effect of morphine.
Sevoflurane Does Not Inhibit Human Platelet Aggregation Induced by Thrombin
Authors: Nozuchi Shinji , Mizobe Toshiki , Aoki Hiroshi , Hiramatsu Noriko , Kageyama Kyoko , Amaya Fumimasa , Uemura Koichi , Fujimiya Tatsuya
Published: November 2003

Background

Sevoflurane reportedly inhibits adenosine diphosphate-induced platelet aggregation by suppressing thromboxane A2 formation. The increase in intracellular calcium concentration that fosters platelet aggregation, however, is also induced by other cell signaling pathways, such as activation of the production of inositol 1,4,5-triphosphate by thrombin. The current study aimed to clarify the net influence of sevoflurane on thrombin-induced platelet aggregation.

Methods

Washed platelets were stimulated by thrombin after incubation with 0.5, 1.0, or 1.5 mM sevoflurane, halothane, or isoflurane. Aggregation curves were measured by an aggregometer. Intracellular calcium concentration was measured fluorometrically using fura-2. Calcium mobilization via plasma membrane calcium channels and the dense tubular system was assessed differentially. Intracellular inositol 1,4,5-triphosphate was measured by radioimmunoassay.

Results

Halothane significantly suppressed aggregation ratios at 5 min compared with those in controls (89 +/- 7%) to 71 +/- 10% (1.0 mM) and 60 +/- 11% (1.5 mM) and the increase in intracellular calcium concentration (controls, 821 +/- 95 nM vs. 440 +/- 124 nM [1.0 mM] or 410 +/- 74 nM [1.5 mM]). Halothane also significantly inhibited release of calcium from the dense tubular system (controls, 220 +/- 48 nM vs. 142 +/- 31 nM [1.0 mM]). Neither sevoflurane nor isoflurane produced a net change in aggregation ratios, intracellular calcium concentration, or calcium mobilization. Halothane (1 mM) significantly suppressed inositol 1,4,5-triphosphate concentrations, whereas neither 1 mM isoflurane nor 1 mM sevoflurane had any effect.

Conclusions

Although sevoflurane has been reported to inhibit human platelet aggregation induced by weak agonists such as adenosine diphosphate, it does not inhibit human platelet aggregation induced by strong agonists such as thrombin.
Approaches to the Prevention of Perioperative Myocardial Ischemia
Authors: Warltier David C. , Pagel Paul S. , Kersten Judy R.
Published: November 2003

Goals for the perioperative management of patients with coronary artery disease include: * Prevent increases in sympathetic nervous system activity: reduce anxiety preoperatively; prevent stress response and release of catecholamines by appropriate use of opioids or volatile anesthetics and beta-adrenoceptor antagonists; beta-blocker therapy should be initiated before and continued during and after the surgical procedure. * Decrease heart rate: reduction in heart rate increases oxygen supply to ischemic myocardium and reduces oxygen demand; the use of beta-blockers is the most effective means to reduce or attenuate deleterious increases in heart rate. * Preserve coronary perfusion pressure: decreases in diastolic arterial pressure in the presence of severe coronary artery stenoses will lead to decreases in blood flow; preservation of perfusion pressure by administration of fluid or phenylephrine or a reduction in anesthetic concentration may be critical. * Decrease myocardial contractility: reduces myocardial oxygen demand and can be accomplished with beta-adrenoceptor antagonists or volatile anesthetics. * Precondition myocardium against stunning and infarction: in the future, this may accomplished by stimulating the adenosine triphosphate- dependent potassium channel with agents such as volatile anesthetics and opioid delta1-receptor agonists.
Hypoxic Brain Tissue following Subarachnoid Hemorrhage
Authors: Hoffman William E. , Wheeler Peggy , Edelman Guy , Charbel Fady T. , Torres Norman J. , Ausman James I.
Published: November 2003

Background

Subarachnoid hemorrhage can lead to cerebral ischemia and irreversible brain injury. The purpose of this study was to determine whether subarachnoid hemorrhage produces changes in brain tissue oxygen pressure, carbon dioxide pressure, or pH during surgery for cerebral aneurysm clipping.

Methods

After institutional review board approval and patient consent, 30 patients undergoing craniotomy for cerebral aneurysm clipping were studied, 15 without and 15 with subarachnoid hemorrhage. Patients with subarachnoid hemorrhage were prospectively separated into groups with modest (Fisher grade 1 or 2; n = 8) and severe bleeds (Fisher grade 3; n = 7). After a craniotomy, a probe was inserted into cortex tissue supplied by the artery associated with the aneurysm. Baseline measures were made in the presence of a 4% end-tidal desflurane level. The end-tidal desflurane level was increased to 9% before clipping of the aneurysm, and a second tissue measurement was made.

Results

The median time of surgery after subarachnoid hemorrhage was 2 days, ranging from 1 to 13 days. During baseline anesthesia, brain tissue oxygen pressure was 17+/-9 mm Hg (mean +/- SD) in control patients, 13+/-9 mm Hg in those with Fisher grade 1 or 2 hemorrhage, and 7+/-6 mm Hg in those with Fisher grade 3 hemorrhage (P<0.05 compared with control). Brain tissue pH was 7.10+/-0.10 in control patients, 7.14+/-0.13 in those with Fisher grade 1 or 2 hemorrhage, and 6.95+/-0.18 in those with with Fisher grade 3 hemorrhage (P<0.05). At a 9% end-tidal desflurane level, brain tissue oxygen pressure increased to 19+/-9 mm Hg and brain tissue pH increased to 7.11+/-0.11 in patients with Fisher grade 3 hemorrhage (P<0.05 for both increases).

Conclusion

These results show that subarachnoid hemorrhage can significantly decrease brain tissue oxygen pressure and pH related to the severity of the bleed. Increasing the desflurane concentration to 9% increased brain tissue oxygen pressure in all patients and brain tissue pH in patients with subarachnoid hemorrhage with baseline acidosis.
Long-lasting Hyperalgesia Induced by Fentanyl in Rats
Authors: Célèrier Evelyne , Rivat Cyril , Jun Yan , Laulin Jean-Paul , Larcher Agnès , Reynier Patrick , Simonnet Guy
Published: November 2003

Background

It has been reported that mu-opioid receptor activation leads to a sustained increase in glutamate synaptic effectiveness at the N-methyl-D-aspartate (NMDA) receptor level, a system associated with central hypersensitivity to pain. One hypothesis is that postoperative pain may result partly from the activation of NMDA pain facilitatory processes induced by opiate treatment per se. The authors tested here the effectiveness of the opiate analgesic fentanyl for eliciting a delayed enhancement in pain sensitivity.

Methods

The consequences of four bolus injections (every 15 min) of fentanyl (20-100 microg/kg per injection, subcutaneously) on immediate (for several hours) and long-term (for several days) sensitivity to nociceptive stimuli in the rat (paw-pressure vocalization test) were evaluated. The effects of the combination of the NMDA-receptor antagonist ketamine (10 mg/kg, subcutaneously) with fentanyl also were assessed.

Results

Fentanyl administration exhibited a biphasic time-dependent effect: first, an early response (for 2-5 h) associated with a marked increase in nociceptive threshold (analgesia), and second, a later response associated with sustained lowering of the nociceptive threshold (5 days for the longest effect) below the basal value (30% of decrease for the maximal effect) indicative of hyperalgesia. The higher the fentanyl dose used, the more pronounced was the fentanyl-induced hyperalgesia. Ketamine pretreatment, which had no analgesic effect on its own, enhanced the earlier response (analgesia) and prevented the development of long-lasting hyperalgesia.

Conclusions

Fentanyl activates NMDA pain facilitatory processes, which oppose analgesia and lead to long-lasting enhancement in pain sensitivity.
Intrathecally Administered cGMP-dependent Protein Kinase Iα Inhibitor Significantly Reduced the Threshold for Isoflurane Anesthesia
Authors: Tao Yuan-Xiang , Hassan Aalya , Johns Roger A.
Published: November 2003

Background

Inhalational anesthetics have been shown to inhibit the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. Previous studies indicated that inhibition of the NO-cGMP pathway decreased the level of consciousness and augmented anesthesia, analgesia, or sedation. The current study investigated the possible involvement of cGMP-dependent protein kinases (PKGs) as major effectors for the NO-cGMP pathway in the anesthetic state.

Methods

After initial baseline determination of the minimum alveolar concentration (MAC), a selective cGMP-dependent protein kinase Ialpha inhibitor, Rp-8-p-CPT-cGMPS, or an NO donor, (NOC-12), were injected intrathecally. Ten minutes later, MAC measurement was repeated. The rats also were evaluated for the presence of locomotor dysfunction by intrathecal administration of Rp-8-p-CPT-cGMPS and NOC-12 in conscious rats.

Results

Rp-8-p-CPT-cGMPS at 25, 50, 100, and 200 microg/10 microl produced a significant decrease from isoflurane control MAC of -4+/-3.1%, 16+/-4.5%, 30+/-5.0%, and 21+/-2.2%, respectively, which was not accompanied by significant changes in either blood pressure or heart rate. In contrast, NOC-12 at 100 microg/10 microl caused an increase from isoflurane control MAC of 23+/-5.8%, which was accompanied by significant decrease in blood pressure but not in heart rate. Rp-8-p-CPT-cGMPS (100 microg/10 microl) produced a significant reversal of isoflurane MAC increase induced by NOC-12 (100 microg/10 microl), which was accompanied by significant reversal of the reduction of blood pressure induced by NOC-12. Locomotor activity was not changed.

Conclusions

The results indicate that cGMP-dependent protein kinase Ialpha inhibitor not only markedly reduces MAC for isoflurane, but also completely blocks the NO-induced increase in isoflurane MAC, which suggests that cGMP-dependent protein kinase Ialpha may mediate the action for the NO-cGMP pathway in anesthetic mechanisms at the spinal cord level.
Propofol-induced Modifications of Cardiomyocyte Calcium Transient and Sarcoplasmic Reticulum Function in Rats
Authors: Guenoun Thierry , Montagne Olivier , Laplace Monique , Crozatier Bertrand
Published: November 2003

Background

Propofol is considered to be an anesthetic agent with few or no negative inotropic effects. This study evaluated a possible direct depressant effect of propofol on sarcoplasmic reticulum Ca2+ accumulation and cardiomyocytes.

Methods

The effects of propofol on intracellular Ca2+ transients were evaluated in isolated rat cardiomyocytes using a microfluorometric technique with Indo-1. Sarcoplasmic reticulum function was also assessed by measuring the oxalate-stimulated Ca2+ uptake from homogenates of rat ventricles.

Results

The Ca2+ uptake capacity of the sarcoplasmic reticulum was decreased by propofol (10(-4) M). Large concentrations of propofol decreased the rate of decrease of the intracellular Ca2+ transient, which resulted in an increase of diastolic Ca2+ when the diastolic interval was decreased. The increased diastolic Ca2+ also resulted in a decrease in Ca2+ transient. This effect appeared for lower doses (10(-5) M) after a short diastolic pause rather than after a long (2- to 3-min) rest (appearing at 10(-4) M).

Conclusions

For doses more than 10(-5) M, propofol induces a Ca2+ uptake capacity impairment of the sarcoplasmic reticulum. This is probably responsible for a slowing of the decrease of the Ca2+ transient, which in turn increases the diastolic Ca2+ for high heart rate. These diastolic modifications may participate in the slight negative inotropic effect of the drug.
Primate Pleuroesophageal Tissue Barrier Frequency Response and Esophageal Pressure Waveform Bandwidth in Health and Acute Lung Injury
Authors: Hartford Craig G. , van Schalkwyk Johan M. , Rogers Geoffrey G. , Turner Martin J.
Published: November 2003

Background

Dynamic intraesophageal pressure (Pes) is used to estimate intrapleural pressure (Ppl) to calculate lung compliance and resistance. This study investigated the nonhuman primate Ppl-Pes tissue barrier frequency response and the dynamic response requirements of Pes manometers.

Methods

In healthy monkeys and monkeys with acute lung injury undergoing ventilation, simultaneous Ppl and Pes were measured directly to determine the Ppl-Pes tissue barrier amplitude frequency response, using the swept-sine wave technique. The bandwidths of physiologic Pes waveforms acquired during conventional mechanical ventilation were calculated using digital low-pass signal filtering.

Results

The Ppl-Pes tissue barrier is amplitude-uniform within the bandwidth of conventional Pes waveforms in healthy and acute lung injury lungs, and does not significantly attenuate Ppl-Pes signal transmission between 1 and 40 Hz. At Pes frequencies higher than conventional clinical regions of interest the Ppl-Pes barrier resonates significantly, is pressure amplitude dependent at low-pressure offsets, and is significantly altered by acute lung injury. Allowing for 5% or less Pes waveform error, the maximum Pes bandwidths during conventional ventilation were 1.9 Hz and 3.4 Hz for physiologic and extreme-case waveforms in healthy lungs and 4.6 Hz and 8.5 Hz during acute lung injury.

Conclusions

In monkeys, the Ppl-Pes tissue barrier has a frequency response suitable for Ppl estimation during low-frequency mechanical ventilation, and Pes manometers should have a minimum uniform frequency response up to 8.5 Hz. However, the Ppl-Pes tissue barrier adversely affects the accurate estimation of dynamic Ppl at high frequencies, with varied airway pressure amplitudes and offsets, such as the Ppl encountered during high-frequency oscillatory ventilation.
Comparison of Blood-conservation Strategies in Cardiac Surgery Patients at High Risk for Bleeding
Authors: Nuttall Gregory A. , Oliver William C. , Ereth Mark H. , Santrach Paula J. , Bryant Sandra C. , Orszulak Thomas A. , Schaff Hartzell V.
Published: November 2003

Background

Aprotinin and tranexamic acid are routinely used to reduce bleeding in cardiac surgery. There is a large difference in agent price and perhaps in efficacy.

Methods

In a prospective, randomized, partially blinded study, 168 cardiac surgery patients at high risk for bleeding received either a full-dose aprotinin infusion, tranexamic acid (10-mg/kg load, 1-mg x kg(-1) x h(-1) infusion), tranexamic acid with pre-cardiopulmonary bypass autologous whole-blood collection (12.5% blood volume) and reinfusion after cardiopulmonary bypass (combined therapy), or saline infusion (placebo group).

Results

There were complete data in 160 patients. The aprotinin (n = 40) and combined therapy (n = 32) groups (data are median [range]) had similar reductions in blood loss in the first 4 h in the intensive care unit (225 [40-761] and 163 [25-760] ml, respectively; P = 0.014), erythrocyte transfusion requirements in the first 24 h in the intensive care unit (0 [0-3] and 0 [0-3] U, respectively; P = 0.004), and durations of time from end of cardiopulmonary bypass to discharge from the operating room (92 [57-215] and 94 [37, 186] min, respectively; P = 0.01) compared with the placebo group (n = 43). Ten patients in the combined therapy group (30.3%) required transfusion of the autologous blood during cardiopulmonary bypass for anemia.

Conclusions

The combination therapy of tranexamic acid and intraoperative autologous blood collection provided similar reduction in blood loss and transfusion requirements as aprotinin. Cost analyses revealed that combined therapy and tranexamic acid therapy were the least costly therapies.
Approximate Entropy as an Electroencephalographic Measure of Anesthetic Drug Effect during Desflurane Anesthesia
Authors: Bruhn Jörgen , Röpcke Heiko , Hoeft Andreas
Published: November 2003

Background

The authors hypothesized that the electroencephalogram (EEG) during higher anesthetic concentrations would show more "order" and less "randomness" than at lower anesthetic concentrations. "Approximate entropy" is a new statistical parameter derived from the Kolmogorov-Sinai entropy formula which quantifies the amount of regularity in data. The approximate entropy quantifies the predictability of subsequent amplitude values of the EEG based on the knowledge of the previous amplitude values. The authors investigated the dose-response relation of the EEG approximate entropy during desflurane anesthesia in comparison with spectral edge frequency 95, median frequency, and bispectral index.

Methods

Twelve female patients were studied during gynecologic laparotomies. Between opening and closure of the peritoneum, end-tidal desflurane concentrations were varied between 0.5 and 1.6 minimum alveolar concentration (MAC). The EEG approximate entropy, median EEG frequency, spectral edge frequency 95, and bispectral index were determined and the performance of each to predict the desflurane effect compartment concentration, obtained by simultaneous pharmacokinetic-pharmacodynamic modeling, was compared.

Results

Electroencephalogram approximate entropy decreased continuously over the observed concentration range of desflurane. The performance of the approximate entropy (prediction probability PK = 0.86 +/- 0.06) as an indicator for desflurane concentrations is similar to spectral edge frequency 95 (PK = 0.86 +/- 0.06) and bispectral index (PK = 0.82 +/- 0.06) and is statistically significantly better than median frequency (PK = 0.78 +/- 0.06).

Conclusions

The amount of regularity in the EEG increases with increasing desflurane concentrations. The approximate entropy could be a useful EEG measure of anesthetic drug effect.
Population Pharmacokinetics of Propofol
Authors: Schüttler Jürgen , Ihmsen Harald
Published: November 2003

Background

Target-controlled infusion is an increasingly common type of administration for propofol. This method requires accurate knowledge of pharmacokinetics, including the effects of age and weight. The authors performed a multicenter population analysis to quantitate the effects of covariates.

Methods

The authors analyzed 4,112 samples of 270 individuals (150 men, 120 women, aged 2-88 yr, weighing 12-100 kg). Population pharmacokinetic modeling was performed using NONMEM (NONMEM Project Group, University of California, San Francisco, CA). Inter- and intraindividual variability was estimated for clearances and volumes. The effects of age, weight, type of administration and sampling site were investigated.

Results

The pharmacokinetics of propofol were best described by a three-compartment model. Weight was found to be a significant covariate for elimination clearance, the two intercompartmental clearances, and the volumes of the central compartment, the shallow peripheral compartment, and the deep peripheral compartment; power functions with exponents smaller than 1 yielded the best results. The estimates of these parameters for a 70-kg adult were 1.44 l/min, 2.25 l/min, 0.92 l/min, 9.3 l, 44.2 l, and 266 l, respectively. For patients older than 60 yr the elimination clearance decreased linearly. The volume of the central compartment decreased with age. For children, all parameters were increased when normalized to body weight. Venous data showed a decreased elimination clearance; bolus data were characterized by increases in the volumes of the central and shallow peripheral compartments and in the rapid distribution clearance (Cl2) and a decrease in the slow distribution clearance (Cl3).

Conclusions

Pharmacokinetics of propofol can be well described by a three-compartment model. Inclusion of age and weight as covariates significantly improved the model. Adjusting pharmacokinetics to the individual patient should improve the precision of target-controlled infusion and may help to broaden the field of application for target-controlled infusion systems.
Additive Inhibition of Nicotinic Acetylcholine Receptors by Corticosteroids and the Neuromuscular Blocking Drug Vecuronium
Authors: Kindler Christoph H. , Verotta Davide , Gray Andrew T. , Gropper Michael A. , Yost C. Spencer
Published: November 2003

Background

Neuromuscular disorders associated with muscular weakness and prolonged paralysis are common in critically ill patients. Acute myopathy has been described in patients receiving a combination therapy of corticosteroids and nondepolarizing neuromuscular blocking drugs for treatment of acute bronchospasm. The cause of this myopathy is not fully established and may involve drug interactions that perturb neuromuscular transmission. To investigate the interaction of corticosteroids with neuromuscular blocking drugs, the authors determined the effects of methylprednisolone and hydrocortisone alone and in combination with vecuronium on fetal (gamma-subunit containing) and adult (epsilon-subunit containing) subtypes of the muscle-type nicotinic acetylcholine receptor.

Methods

Functional channels were expressed in Xenopus laevis oocytes and activated with 1 microM acetylcholine. The resulting currents were recorded using a whole cell two-electrode voltage clamp technique.

Results

Both forms of the muscle-type acetylcholine receptor were potently inhibited by methylprednisolone and hydrocortisone, with concentrations producing 50% inhibition in the range of 400-600 microM and 1-2 mM, respectively. The corticosteroids produced noncompetitive antagonism of the muscle-type nicotinic acetylcholine receptor at clinical concentrations. Both receptor forms were also inhibited, even more potently, by vecuronium, with a concentration producing 50% inhibition in the range of 1-2 nM. Combined application of vecuronium and methylprednisolone showed additive effects on both receptor forms, which were best described by a two-site model, with each site independent.

Conclusions

The enhanced neuromuscular blockade produced when corticosteroids are combined with vecuronium may augment pharmacologic denervation and contribute to the pathophysiology of prolonged weakness observed in some critically ill patients.
The Dose–Response of Intrathecal Sufentanil Added to Bupivacaine for Labor Analgesia
Authors: Wong Cynthia A. , Scavone Barbara M. , Loffredi Mariann , Wang Warren Y. , Peaceman Alan M. , Ganchiff Jeanne N.
Published: November 2003

Background

Regional analgesia for labor often is initiated with an intrathecal injection of a local anesthetic and opioid. The purpose of this prospective, randomized, blinded study was to determine the optimal dose of intrathecal sufentanil when combined with 2.5 mg bupivacaine for labor analgesia.

Methods

One hundred seventy parous parturients with cervical dilation between 3-5 cm were randomized to receive intrathecal 0 (control), 2.5, 5.0, 7.5, or 10.0 microg sufentanil combined with 2.5 mg bupivacaine, followed by a lidocaine epidural test dose, for initiation of analgesia (34 patients in each group). Visual analog scores and the presence of nausea, vomiting, and pruritus were determined every 15 min until the patient requested additional analgesia. Fetal heart rate tracings were compared between groups.

Results

Groups were similar for age, height, weight, oxytocin dose, duration of labor, and baseline visual analog scores. Duration of action was significantly shorter for control patients (39 +/- 25 min [mean +/- SD]) compared with those administered sufentanil, all doses (93 +/- 32, 93 +/- 47, 94 +/- 33, 97 +/- 39 min), but was not different among groups administered 2.5, 5.0, 7.5, or 10.0 microg sufentanil. More patients who received 10 microg sufentanil reported nausea and vomiting than did control patients. The severity of pruritus increased with administration of 7.5 and 10.0 microg sufentanil. There was no difference in fetal heart rate changes among groups.

Conclusions

Intrathecal bupivacaine (2.5 mg) without sufentanil did not provide satisfactory analgesia for parous patients. However, bupivacaine combined with 2.5 microg sufentanil provided analgesia comparable to higher doses, with a lower incidence of nausea and vomiting and less severe pruritus.
Pharmacokinetics of Human Cerebral Opioid Extraction
Authors: Metz Christoph , Göbel Lothar , Gruber Michael , Hoerauf Klaus H. , Taeger Kai
Published: November 2003

Background

The pharmacodynamic differences in time to onset and dissipation of effect of sufentanil, fentanyl, and alfentanil probably result from different rates of blood-brain equilibration. The authors investigated this hypothesis in humans.

Methods

After simultaneous central venous bolus application of sufentanil (10 microg), fentanyl (100 microg), and alfentanil (1,000 microg), arterial and jugular bulb blood samples were drawn simultaneously at 20, 30, 45, 60, 75, 90, 105, 120, 140, 160, 180, 210, 240, 300, 360, and 420 s from 19 patients during the postacute stage of head injury with normal intracranial pressure, cerebral perfusion pressure, and cerebral oxygen metabolism during normocapnia.

Results

Peak brain concentration, indicated by equilibrium between arterial and jugular bulb opioid concentrations, was achieved for alfentanil at 45 s, for sufentanil at 5 min, and for fentanyl at 6 min. The corresponding median time intervals (fifth and ninety-fifth percentiles) to reach 50% of peak brain concentration were 15 (14-18), 25 (18-38) and 35 (25-45) s, respectively. Uptake was highest 20 s after bolus and decreased continuously for fentanyl and sufentanil, whereas alfentanil uptake was biphasic. The ratio of the relative amounts of sufentanil, fentanyl, and alfentanil retained in the brain at peak brain concentration was 1x:x6x:x90.

Conclusions

The differences in the time lag between changes in serum concentrations and drug effect after bolus application of nearly equipotent doses of sufentanil, fentanyl, and alfentanil originate from the different times required to reach blood-brain equilibration, mainly depending on different levels and different time profiles of arterial blood concentrations caused by the different tissue distribution volumes.
The Influence of Drug-induced Low Plasma Cholinesterase Activity on the Pharmacokinetics and Pharmacodynamics of Mivacurium
Authors: Østergaard Doris , Rasmussen Søren N. , Viby-Mogensen Jørgen , Pedersen Niels A. , Boysen Rikke
Published: November 2003

Background

The short duration of action of mivacurium results from its rapid hydrolysis by plasma cholinesterase. Bambuterol, an oral bronchodilator, has an inhibiting effect on plasma cholinesterase. The purpose of this study was to evaluate the effect of bambuterol-induced low plasma cholinesterase activity on the pharmacokinetics and pharmacodynamics of mivacurium.

Methods

Fourteen patients received 20 mg bambuterol and 14 patients received placebo orally 2 h before induction of anesthesia. During anesthesia the neuromuscular block was monitored at the thumb using train-of-four nerve stimulation every 12 s and mechanomyography. The times to different levels of neuromuscular recovery after 0.2 mg/kg mivacurium were measured. The concentrations in venous blood of the three isomers and the metabolites of mivacurium were measured using high-performance liquid chromatography.

Results

Plasma cholinesterase activity was inhibited a median of 90% (range, 67-97%) after bambuterol. The time to first response to train-of-four nerve stimulation was 15 min (range, 9-21 min) and 59 min (range, 32-179 min) in patients receiving placebo and bambuterol, respectively. The estimated clearances of the isomers were significantly lower and the elimination half-lives of all three isomers significantly prolonged in patients receiving bambuterol. No difference was seen in elimination half-lives of the metabolites. The elimination rate constant from the effect compartment and the potency of mivacurium was not affected by bambuterol.

Conclusion

A 90% inhibition of plasma cholinesterase activity significantly reduced clearance of the isomers of mivacurium. Correspondingly, the duration of action of 0.2 mg/kg mivacurium was prolonged three- to fourfold, compared with patients not administered bambuterol.
Ropivacaine, 0.1%, Plus Sufentanil, 0.5 μg/ml, versus Bupivacaine, 0.1%, Plus Sufentanil, 0.5 μg/ml, Using Patient-controlled Epidural Analgesia for Labor
Authors: Fischer Catherine , Blanié Pierre , Jaouën Envel , Vayssière Christophe , Kaloul Ismaël , Coltat Jean-Claude
Published: November 2003

Background

This study compared the administration of 0.1% ropivacaine and 0.5 microg/ml sufentanil with that of 0.1% bupivacaine and 0.5 microg/ml sufentanil via patient-controlled epidural analgesia route during labor.

Methods

Two hundred healthy pregnant women at term with a single fetus with a vertex fetal presentation were randomized in a double-blind fashion to receive either 0.1% ropivacaine and 0.5 microg/ml sufentanil or 0.1% bupivacaine and 0.5 microg/ml sufentanil using a patient-controlled epidural analgesia pump (5-ml bolus dose, 10-min locked-out period, no basal infusion). Pain score on a visual analog scale, Bromage score (0-3), level of sensory block, patient-controlled epidural analgesia ratio, drug use, supplemental boluses, and side effects were recorded at 30 min and then hourly. Mode of delivery, duration of first and second stages of labor, umbilical cord pH, Apgar scores of the newborn, and a measure of maternal satisfaction were recorded after delivery.

Results

No differences were seen between the two groups for pain scores on a visual analog scale during labor, volume of anesthetic solution used, mode of delivery, or side effects. Motor block during the first stage of labor was significantly less in the ropivacaine group than in the bupivacaine group (no motor block in 97.8 of patients vs. 88.3%, respectively; P < 0.01). Duration of the second stage of labor was shorter in the ropivacaine group (1.3 +/- 1.0 vs. 1.5 +/- 1.2 h [mean +/- SD]; P < 0.05). Maternal satisfaction was greater in the bupivacaine group (91 +/- 13 mm for contraction, 89 +/- 19 mm for delivery on a visual scale: 0 = not satisfied at all, 100 = fully satisfied) than in the ropivacaine group (84 +/- 21 and 80 +/- 25 mm; P < 0.0001). Patients in the ropivacaine group requested more supplemental boluses to achieve analgesia during the second stage of labor than those in the bupivacaine group (29.7 vs. 19.8%, respectively, requested one or more supplemental boluses; P < 0.05).

Conclusions

Delivered as patient-controlled epidural analgesia, 0.1% ropivacaine and 0.5 microg/ml sufentanil produce less motor block but are clinically less potent than 0.1% bupivacaine and 0.5 microg/ml sufentanil.
Multiport Epidural Catheters
Authors: Leighton Barbara L. , Topkis William G. , Gross Jeffrey B. , Arkoosh Valerie A. , Lee Sung-Hee R. , Huffnagle H. Jane , Huffnagle Suzanne L.
Published: November 2003

Background

Multiport epidural catheters are popular; however, the reliability of the air test has not been evaluated with this catheter design. The authors determined the effectiveness of aspirating for blood and the air test in detecting intravascular multiorifice epidural catheters.

Methods

Three hundred women in labor underwent placement of a blunt-tip, three-hole, 20-gauge, lumbar epidural catheter. If there were no signs of spinal anesthesia, 3 ml lidocaine or bupivacaine was injected and the patient was observed for signs of spinal anesthesia. If there were no signs of spinal anesthesia, the authors injected 1 ml air through the epidural catheter while listening to the maternal precordium using a Doppler fetal heart rate monitor. Catheters through which blood was aspirated were air-tested and replaced. Patients with air-test-positive, blood-aspiration-negative catheters received 100 mg lidocaine through the catheter and were questioned about toxicity symptoms. The authors injected bupivacaine-fentanyl through aspiration-negative,air-test-negative catheters and recorded the sensory analgesic level 20 min later.

Results

The authors aspirated cerebrospinal fluid through one catheter and documented intravascular placement in 11 catheters. Results of the air test and blood aspiration were positive for eight catheters. Blood could not be aspirated from one air-test-positive catheter; perioral numbness developed in the patient after lidocaine injection. Blood was freely aspirated from two air-test-negative catheters. In the remaining 288 catheters, bupivacaine-fentanyl injection produced epidural analgesia in 279 patients and no effect in 9 patients.

Conclusions

The authors obtained false-negative results with both catheter aspiration and the air test. Fractionating the local anesthetic dose is important when using multiorifice epidural catheters.
Pressure Support Ventilation versus Continuous Positive Airway Pressure with the Laryngeal Mask Airway
Authors: Brimacombe Joseph , Keller Christian , Hörmann Christoph
Published: November 2003

Background

The authors tested the hypothesis that pressure support ventilation (PSV) provides more effective gas exchange than does unassisted ventilation with continuous positive airway pressure (CPAP) in anesthetized adult patients treated using the laryngeal mask airway.

Methods

Forty patients were randomized to two equal-sized crossover groups, and data were collected before surgery. In group 1, patients underwent CPAP, PSV, and CPAP in sequence. In group 2, patients underwent PSV, CPAP, and PSV in sequence. PSV comprised positive end expiratory pressure set at 5 cm H2O and inspiratory pressure support set at 5 cm H2O above positive end expiratory pressure. CPAP was set at 5 cm H2O. Each ventilatory mode was maintained for 10 min. The following data were recorded every minute for the last 5 min of each ventilatory mode and the average reading taken: end tidal carbon dioxide, oxygen saturation, expired tidal volume, leak fraction, respiratory rate, noninvasive mean arterial pressure, and heart rate.

Results

In both groups, PSV showed lower end tidal carbon dioxide (P < 0.001), higher oxygen saturation, (P < 0.001), and higher expired tidal volume (P < 0.001) compared with CPAP. In both groups, PSV had similar leak fraction, respiratory rate, mean arterial pressure, and heart rate compared with CPAP. In group 1, measurements for CPAP were similar before and after PSV. In group 2, measurements for PSV were similar before and after CPAP.

Conclusion

The authors concluded that PSV provides more effective gas exchange than does unassisted ventilation with CPAP during LMA anesthesia while preserving leak fraction and hemodynamic homeostasis.
The Fiberscopic Findings of the Epidural Space in Pregnant Women
Authors: Igarashi Takashi , Hirabayashi Yoshihiro , Shimizu Reiju , Saitoh Kazuhiko , Fukuda Hirokazu , Suzuki Hideo
Published: November 2003

Background

The spread of epidural analgesia is facilitated by pregnancy. Changes in the epidural structure during pregnancy may affect the spread of analgesia in pregnant women. To investigate the changes in the epidural space produced by pregnancy, the authors performed epiduroscopy in pregnant women.

Methods

Using a flexible fiberscope, the authors evaluated the epidural space in 73 women undergoing lumbar epidural anesthesia. Patients were classified into three groups: a nonpregnant group (n = 21), a first trimester pregnant group (8-13 weeks, n = 23), and a third-trimester pregnant group (27-39 weeks, n = 29). A 17-gauge Tuohy needle was inserted using the paramedian technique and the loss-of-resistance method with 5 ml air. The epiduroscope was introduced into the lumbar epidural space via the Tuohy needle and was advanced approximately 10 cm in a cephalad direction from the needle tip within the epidural space. The differences in the epidural space among the three groups then was evaluated.

Results

The epiduroscopy showed that the epidural pneumatic space, after injection of a given amount of air, was narrower and the density of the vascular network greater in the third-trimester group than in the other two groups. The amount of engorged blood vessels was greater in the third and first trimester groups than in the nonpregnant group. The amount of bleeding at the needle tip and the amount of fatty and fibrous connective tissue did not differ among the three groups.

Conclusions

Epidural blood vessels become engorged in the first trimester; the density of the vascular networks increase in the third trimester. These changes in the epidural space during pregnancy may affect the spread of epidural analgesia in pregnant women.
Port-access Minimally Invasive Cardiac Surgery Increases Surgical Complexity, Increases Operating Room Time, and Facilitates Early Postoperative Hospital Discharge
Authors: Chaney Mark A. , Durazo-Arvizu Ramón A. , Fluder Elaine M. , Sawicki Kristina J. , Nikolov Mihail P. , Blakeman Bradford P. , Bakhos Mamdouh
Published: November 2003

Background

Proposed advantages of port-access cardiac surgery have yet to be substantiated. The authors retrospectively compared patients undergoing port-access cardiac surgery with a matched group undergoing conventional cardiac surgery.

Methods

Forty-six patients who underwent port-access cardiac surgery were matched with 46 who underwent conventional cardiac surgery. Absolute criteria for matching included morning-of-surgery admission, procedure undergone, and care being delivered by one of two surgeons. If possible, matching included care delivered by one of two anesthesiologists. Patients were matched as closely as possible for preoperative demographic and clinical characteristics.

Results

All 46 pairs of patients were matched for procedure and admitted the morning of surgery. All 92 operations were performed by one of two surgeons, and 89% were performed by one of two anesthesiologists. Preoperative demographic and clinical characteristics were equivalent between groups. Compared with conventional cardiac surgery, port-access cardiac surgery increased surgical complexity (it almost tripled cardiopulmonary bypass time during coronary artery bypass grafting and increased it almost 40% during mitral valve procedures) and increased total operating room time (P < 0.0001). Port-access cardiac surgery had no beneficial effect on earlier postoperative extubation, decreased incidence of atrial fibrillation, or intensive care unit time, yet it decreased postoperative duration of stay (P = 0.029, all patients), a benefit observed primarily in patients undergoing coronary artery bypass grafting (P = 0.002).

Conclusions

This retrospective analysis revealed that port-access cardiac surgery increases surgical complexity, increases operating room time, has no effect on earlier postoperative extubation or decreased incidence of atrial fibrillation or intensive care unit time, and may facilitate postoperative hospital discharge (primarily in patients undergoing coronary artery bypass grafting). Properly designed prospective investigation is necessary to ascertain whether port-access cardiac surgery truly offers any benefits over conventional cardiac surgery.
Pain Relief in Complex Regional Pain Syndrome due to Spinal Cord Stimulation Does Not Depend on Vasodilation
Authors: Kemler Marius A. , Barendse Gerard A. M. , van Kleef Maarten , Egbrink Mirjam G. A. oude
Published: November 2003

Background

Spinal cord stimulation (SCS) is known to relieve pain in patients with complex regional pain syndrome (CRPS) and, in general, to cause vasodilation. The vasodilatory effect of SCS is hypothesized to be secondary to inhibition of sympathetically mediated vasoconstriction, or through antidromic impulses resulting in release of vasoactive substances. The aim of the present study was to assess whether pain relief in CRPS after SCS is, in fact, dependent on vasodilation. In addition, we tried to determine which of the potential mechanisms may cause the vasodilatory effect that is generally found after SCS.

Methods

Twenty-four of 36 patients with unilateral CRPS responded to the test of SCS. Twenty-two of these 24 responders (hand, n = 14; foot, n = 8) who had undergone previous sympathectomy were enrolled for the study. In addition, 20 control subjects (10 controls for each extremity) were studied. By means of laser Doppler flowmetry, the skin microcirculation of the patients was measured bilaterally while the SCS system was switched off and while it was activated. Control subjects (n = 20) were tested once only. The ratio of the rest flow at heart level and the dependent position was defined as the vasoconstriction index.

Results

Both in affected hands and feet, patients were found to have lower vasoconstriction indices (P < 0.01) as compared with controls, indicating a decreased sympathetic tone. Applying SCS did not result in any microcirculatory change as compared with baseline or the contralateral clinically unaffected side.

Conclusions

The current study failed to show that SCS influences skin microcirculation in patients with CRPS and a low sympathetic tone. Therefore, we may conclude that pain relief in CRPS due to SCS is possible without vasodilation. Because sympathetic activity was greatly decreased in our patients, these results support the hypothesis that the vasodilation that is normally found with SCS is due to an inhibitory effect on sympathetically maintained vasoconstriction.
Differential Block of Fast and Slow Inactivating Tetrodotoxin-sensitive Sodium Channels by Droperidol in Spinal Dorsal Horn Neurons
Authors: Olschewski Andrea , Bräu Michael E. , Hempelmann Gunter , Vogel Werner , Safronov Boris V.
Published: November 2003

Background

Dorsal horn neurons of the spinal cord participate in neuronal pain transmission. During spinal and epidural anesthesia, dorsal horn neurons are exposed to local anesthetics and opioids. Droperidol is usually given with opioids to avoid nausea and vomiting. A recently developed method of "entire soma isolation" has made it possible to study directly the action of droperidol on different components of Na+ current in dorsal horn neurons.

Methods

Using a combination of the whole-cell patch-clamp recording from spinal cord slices and the entire soma isolation method, we studied the direct action of droperidol on two types of Na+ currents in dorsal horn neurons of young rats.

Results

The tetrodotoxin-sensitive Na+ current in isolated somata consisted of a fast inactivating (tauF, 0.5-2 ms; 80-90% of the total amplitude) and a slow inactivating (tauS, 6-20 ms; 10-20% of the total amplitude) component. Droperidol, at concentrations relevant for spinal and epidural anesthesia, selectively and reversibly suppressed the fast component with a half-maximum inhibiting concentration (IC50) of 8.3 microm. The slow inactivating component was much less sensitive to droperidol; the estimated IC50 value was 809 microm.

Conclusions

Droperidol selectively blocks fast Na+ channels, the fast and slow components of the Na+ current in dorsal horn neurons are carried through pharmacologically distinct types of Na+ channels, and the effects of droperidol differ from those of local anesthetics and tetrodotoxin, which equipotently suppress both components. Droperidol may be suggested as a pharmacologic tool for separation of different types of inactivating tetrodotoxin-sensitive Na+ channel.
Morphine Inhibits NF-κB Nuclear Binding in Human Neutrophils and Monocytes by a Nitric Oxide–dependent Mechanism
Authors: Welters Ingeborg D. , Menzebach Axel , Goumon Yannick , Cadet Patrick , Menges Thilo , Hughes Thomas K. , Hempelmann Gunter , Stefano George B.
Published: November 2003

Background

The transcription factor NF-kappaB plays a pivotal role in gene expression of inflammatory mediators such as cytokines or adhesion molecules. NF-kappaB-mediated transcriptional activation of these genes is inhibited by nitric oxide (NO) in a variety of cells, including monocytes. Morphine mediates NO release in a naloxone antagonizable manner in monocytes and neutrophils.

Methods

The influence of morphine on NF-kappaB activation was investigated in a whole-blood flow cytometric assay. A specific antibody against the p65 subunit of NF-kappaB was used and detected by fluoresceine-isothiocyanate-labeled anti-immunoglobulin G. Nuclei were stained with propidium iodide. Leukocyte subpopulations were evaluated by gating on neutrophils and monocytes. The median fluorescence channel was determined. Different morphine concentrations (50 nm, 50 microm, 1 mm) and incubation intervals (10-150 min) were used.

Results

Morphine inhibits lipopolysaccharide-induced NF-kappaB nuclear binding in human blood neutrophils and monocytes in a time-, concentration-, and naloxone-sensitive-dependent manner. Similar effects were achieved with the NO donor S-nitroso-N-acetyl-pencillamine and the antioxidant N-acetyl-cysteine. The NO synthase inhibitors Nomega-nitro-l-arginine-methyl-esther and Nomega-nitro-l-arginine completely abolished the morphine-induced attenuation of NF-kappaB nuclear binding, demonstrating that the inhibitory action is mediated by NO release.

Conclusion

Morphine causes immunosuppression, at least in part, via the NO-stimulated depression of NF-kappaB nuclear binding.