bluuebunny/crossref_metadata_2025 huggingface dataset:
Diffusion of Xenon and Nitrous Oxide into the Bowel
Authors: Reinelt Helmut , Schirmer Uwe , Marx Thomas , Topalidis Pantelis , Schmidt Michael
Published: November 2003

Background

Nitrous oxide diffuses easily from blood into air filled spaces. Xenon is also a relatively insoluble gas, like nitrous oxide. Therefore, the authors measured xenon diffusion into obstructed bowel segments during xenon anesthesia and compared this with nitrous oxide and nitrogen diffusion.

Methods

Twenty-one pentobarbital-anesthetized pigs were randomly assigned to three groups to receive either xenon-oxygen, nitrous oxide-oxygen, or nitrogen-oxygen (75%-25%), respectively. In each animal four bowel segments of 15-cm length were isolated. A pressure-measuring catheter was inserted into the lumen, and 30 ml of room air was injected into the segments. Anesthesia with the selected gas mixture was performed for 4 h. Pressure in the segments was measured continuously. The volume of gaseous bowel content was measured on completion of the study.

Results

The median volume of bowel gas in animals breathing nitrous oxide was 88.0 ml as compared with 39.0 ml with xenon anesthesia and 21.5 ml in the nitrogen-oxygen group. After 4 h of anesthesia, the intraluminal pressures in the nitrous oxide group were found to be significantly greater than in the control group and in the xenon group.

Conclusions

The amount of diffused gas was significantly lower during xenon anesthesia than with nitrous oxide anesthesia but greater than with controls. Blood solubility can therefore be regarded as an important factor influencing gas diffusion into air filled cavities.
Administration of Endocannabinoids Prevents a Referred Hyperalgesia Associated with Inflammation of the Urinary Bladder
Authors: Farquhar-Smith W. Paul , Rice Andrew S. C.
Published: November 2003

Background

Referred hyperalgesia to a somatopically appropriate superficial site is a cardinal symptom of visceral inflammatory pain and has been demonstrated after turpentine-induced urinary bladder inflammation in the rat. The authors examined the effect of the endocannabinoids anandamide and palmitoylethanolamide on the referred hyperalgesia associated with this model.

Methods

After measurement of baseline limb withdrawal latencies to a noxious heat stimulus, the bladders of 50 female Wistar rats were inflamed by intravesical administration of 0.5 ml 50% turpentine. Ten or 25 mg/kg of anandamide or palmitoylethanolamide or vehicle were administered immediately before introduction of turpentine. Antagonists to both the cannabinoid CB1 and CB2 receptors were coadministered with the higher dose of endocannabinoids. Latencies were recorded 2, 4, 6, 8, and 24 h after removal of turpentine. The difference between forelimb and hind limb withdrawal latencies was plotted against time, and areas under these curves were compared.

Results

Inflammation of the urinary bladder was associated with a relative thermal hyperalgesia referred to the hind limb. Anandamide and palmitoylethanolamide attenuated this referred hyperalgesia at doses of 10 and 25 mg/kg. The CB1 receptor antagonist SR141716A reduced the antihyperalgesic effect of anandamide, but the CB2 antagonist SR144528 did not. Coadministration of SR141716A with palmitoylethanolamide did not affect the antihyperalgesic effect but was reduced by SR144528.

Conclusions

Anandamide (via CB1 receptors) and palmitoylethanolamide (putatively via CB2 receptors) attenuated a referred hyperalgesia in a dose-dependent fashion. CB1 and CB2 receptors are strategically situated to influence the nerve growth factor-driven referred hyperalgesia associated with inflammation of the urinary bladder. These data implicate cannabinoids as a novel treatment for vesical pain.
Modeling Population Pharmacokinetics of Lidocaine
Authors: Kuipers Jette A. , Boer Fred , de Roode Annemiek , Olofsen Erik , Bovill James G. , L. Burm Anton G.
Published: November 2003

Background

Inclusion of cardiac output and other physiologic parameters, in addition to or instead of, demographic variables might improve the population pharmacokinetic modeling of lidocaine.

Methods

Thirty-one patients were included in a population pharmacokinetic study of lidocaine. After bolus injection of lidocaine (1 mg/kg), 22 or 10 blood samples per patient were taken from a radial artery. During the experiment, cardiac output was measured using a thoracic electrical bioimpedance method. The following four population pharmacokinetic models were constructed and their performances investigated: a model with no covariates, a model with cardiac output as covariate, a model with demographic covariates, and a model with both cardiac output and demographic characteristics as covariates. Model discrimination was performed with the likelihood ratio test.

Results

Inclusion of cardiac output resulted in a significant improvement of the pharmacokinetic model, but inclusion of demographic covariates was even better. However, the best model was obtained by inclusion of both demographic covariates and cardiac output in the pharmacokinetic model.

Conclusions

When population pharmacokinetic models are used for individualization of dosing schedules, physiologic covariates, e.g., cardiac output, can improve their ability to predict the individual kinetics.
Minimum Local Analgesic Dose of Intrathecal Bupivacaine in Labor and the Effect of Intrathecal Fentanyl
Authors: Stocks Gary M. , Hallworth Stephen P. , Fernando Roshan , England Adrian J. , Columb Malachy O. , Lyons Gordon
Published: November 2003

Background

Combining bupivacaine with fentanyl for intrathecal analgesia in labor is well recognized, but dosages commonly used are arbitrarily chosen and may be excessive. This study aimed to determine the median effective dose (ED50) of intrathecal bupivacaine, defined as the minimum local analgesic dose (MLAD), and then use this to assess the effect of different doses of fentanyl.

Methods

In this double-blind, randomized, prospective study, 124 parturients receiving combined spinal epidural analgesia at 2-6-cm cervical dilatation were allocated to one of four groups to receive bupivacaine alone or with 5, 15, or 25 microg fentanyl, using the technique of up-down sequential allocation. Analgesic effectiveness was assessed using 100-mm visual analog pain scores, with less than or equal to 10 mm within 15 min defined as effective. MLAD was calculated using the formula of Dixon and Massey. Pruritus and duration of spinal analgesia were also recorded.

Results

Minimum local analgesic dose of intrathecal bupivacaine was 1.99 mg (95% confidence interval, 1.71, 2.27). There were similar significant reductions in MLAD (P < 0.001) for all bupivacaine-fentanyl groups compared with bupivacaine control. There was a dose-dependent increase in both pruritus and duration of spinal analgesia with increasing fentanyl (P < 0.0001).

Conclusion

Under the conditions of this study, the addition of intrathecal fentanyl 5 microg offers a similar significant bupivacaine dose-sparing effect as 15 and 25 microg. Analgesia in the first stage of labor can be achieved using lower doses of fentanyl, resulting in less pruritus but with a shortening of duration of action.
Preemptive Analgesic Effects of Ketorolac in Ankle Fracture Surgery
Authors: Norman Peter H. , Daley M. Denise , Lindsey Ronald W.
Published: November 2003

Background

Preemptive analgesia has been difficult to show in human experiments. If ketorolac has preemptive effects, then there may be an advantage to administering it at the beginning of surgery despite the potential for increased blood loss.

Methods

The authors performed a randomized, double-blind, controlled trial of 48 patients scheduled for ankle fracture surgery in a county trauma hospital. Anesthesia management was standardized and included adequate opioid analgesia (5 microg/kg fentanyl and 0.1 mg/kg morphine). Intravenous 30 mg ketorolac was administered to 23 patients before tourniquet inflation and to 25 patients after tourniquet inflation. Visual analog scale pain scores, morphine patient-controlled analgesia consumption, nausea-vomiting, and postoperative bleeding were measured.

Results

The 23 patients given ketorolac before tourniquet inflation had no increase in pain postoperatively compared with their preoperative baseline (P = 0.280). The 25 patients who received ketorolac minutes later after tourniquet inflation had significant increases in their postoperative pain compared with their preoperative baseline (P = 0.00116). This effect was short-lived, and by 6 h the pain score in this group was not significantly more than it was preoperatively. Intergroup comparison showed a lower visual analog scale score at 2 (P = 0.0203) and 4 h (P = 0.00549) in the preemptive group and lower nausea scores at hour 6 (P = 0.00704). There was no difference in patient-controlled analgesia consumption between groups.

Conclusions

Intravenous 30 mg ketorolac appears to have preemptive analgesic effects in patients undergoing ankle fracture repair. Ketorolac administered before tourniquet inflation prevents postoperative pain being perceived as more intense than preoperative pain.
The Effects of CO2on Respiratory Mechanics in Anesthetized Paralyzed Humans
Authors: D’Angelo Edgardo , Salvo Calderini Ida , Tavola Mario
Published: November 2003

Background

There is little information concerning the carbon dioxide-related effects on respiratory mechanics in anesthetized, paralyzed subjects; however, hypocapnia or hypercapnia is often permitted in patients with severe brain injury or acute respiratory distress syndrome. Therefore, the carbon dioxide dependence of respiratory mechanics in healthy anesthetized, paralyzed subjects was investigated.

Methods

Interrupter resistance (Rint), additional tissue viscoelastic resistance (deltaR), and quasi-static elastance (Est) of lung (L) and chest wall were assessed by means of the rapid end-inspiratory occlusion method in two groups of seven healthy paralyzed subjects anesthetized with diazepam or isoflurane. They underwent ventilation with a fixed pattern and hyperoxic gas mixtures with different fractions of inspired carbon dioxide (FICO2) to produce a partial pressures of arterial carbon dioxide (PaCO2) of 24.4 +/- 3.4, 39.6 +/- 3.2, and 62 +/- 4.1 (SD) mmHg.

Results

Chest wall mechanics and Est,L were unaffected by PaCO2 changes. With diazepam anesthesia, Rint,L decreased linearly, with increasing PaCO2, from 2.3 to 1.4 cm H2O.s.l(-1), whereas deltaR,L decreased from 2 to 1.7 cm H2O.s.l(-1), though not significantly. With isoflurane anesthesia, the decrease of Rint,L (0.2 +/- 0.5 cm H2O.s.l(-1)) was not significant, and deltaRL remained unchanged. With diazepam, Rint,L was 45 (hypercapnia) to 110% (hypocapnia) greater than with isoflurane.

Conclusions

Changes of PaCO2 from 20-65 mmHg cause increasing bronchodilation in anesthetized, paralyzed subjects, this effect being attenuated or abolished by drugs (e.g., halogenated anesthetics) that depress smooth muscle tone substantially. The carbon dioxide bronchodilating effects are probably direct for peripheral structures and are paralleled by a tendency of lung tissue resistance to decrease. Because local PaCO2-related changes in bronchomotor tone promote VA/Q matching, this mechanism should be impaired by anesthetics that cause bronchodilation.
Minimum Alveolar Concentration (MAC) of Xenon with Sevoflurane in Humans
Authors: Nakata Yoshinori , Goto Takahisa , Ishiguro Yoshiki , Terui Katsuo , Kawakami Hiromasa , Santo Masayuki , Niimi Yoshinari , Morita Shigeho
Published: November 2003

Background

Although more than 30 yr ago the minimum alveolar concentration (MAC) of xenon was determined to be 71%, that previous study had technological limitations, and no other studies have confirmed the MAC value of xenon since. The current study was designed to confirm the MAC value of xenon in adult surgical patients using more modern techniques.

Methods

Sixty patients were anesthetized with sevoflurane with or without xenon. They were randomly allocated to one of four groups; patients in group 1 received no xenon, whereas those in groups 2, 3, and 4 received end-tidal concentrations of 20, 40, and 60%, respectively (n = 15 each group). Target end-tidal sevoflurane concentrations were chosen using the "up-and-down" method in each group. After steady state sevoflurane and xenon concentrations were maintained for at least 15 min, each patient was monitored for a somatic response at surgical incision. Somatic response was defined as any purposeful bodily movement. The MAC of sevoflurane and its reduction by xenon was evaluated using the multiple independent variable logistic regression model.

Results

The interaction coefficient of the multiple variable logistic regression was not significantly different from zero (P = 0.143). The MAC of xenon calculated as xenon concentration that would reduce MAC of sevoflurane to 0% was 63.1%.

Conclusions

The authors could not determine whether interaction in blocking somatic responses in 50% of patients is additive. The MAC of xenon is in the range of the values that were predicted in a previous study.
Effects of Ketamine and Its Isomers on Ischemic Preconditioning in the Isolated Rat Heart
Authors: Molojavyi Andrei , Preckel Benedikt , Comfère Thomas , Müllenheim Jost , Thämer Volker , Schlack Wolfgang
Published: November 2003

Background

Ischemic preconditioning protects the heart against subsequent ischemia. Opening of the adenosine triphosphate-sensitive potassium (KATP) channel is a key mechanism of preconditioning. Ketamine blocks KATP channels of isolated cardiomyocytes. The authors investigated the effects of ketamine and its stereoisomers on preconditioning.

Methods

Isolated rat hearts (n = 80) underwent 30 min of no-flow ischemia and 60 min of reperfusion. Two groups with eight hearts each underwent the protocol without intervention (control-1 and control-2), and, in eight hearts, preconditioning was elicited by two 5-min periods of ischemia before the 30 min ischemia. In the six treatment groups (each n = 8), ketamine, R(-)- or S(+)-ketamine were administered at concentrations of 2 or 20 microg/ml before preconditioning. Eight hearts received 20 microg/ml R(-)-ketamine before ischemia. Left ventricular (LV) developed pressure and creatine kinase (CK) release during reperfusion were determined as variables of ventricular function and cellular injury.

Results

Baseline LV developed pressure was similar in all groups: 104 +/- 28 mmHg (mean +/- SD). Controls showed a poor recovery of LV developed pressure (17 +/- 8% of baseline) and a high CK release (70 +/- 17 IU/g). Ischemic preconditioning improved recovery of LV developed pressure (46 +/- 14%) and reduced CK release (47 +/- 17 IU/g, both P < 0.05 vs. control-1). Ketamine (2 microg/ml) and 2 or 20 microg/ml S(+)-ketamine had no influence on recovery of LV developed pressure compared with preconditioning (47 +/- 18, 43 +/- 8, 49 +/- 36%) and CK release (39 +/- 8, 30 +/- 14, 41 +/- 25 IU/g). After administration of 20 microg/ml ketamine and 2 or 20 microg/ml R(-)-ketamine, the protective effects of preconditioning were abolished (LV developed pressure-recovery, 16 +/- 14, 22 +/- 21, 18 +/- 11%; CK release, 67 +/- 11, 80 +/- 21, 82 +/- 41 IU/g; each P < 0.05 vs. preconditioning). Preischemic treatment with R(-)-ketamine had no effect on CK release (74 +/- 8 vs. 69 +/- 9 IU/g in control-2, P = 0.6) and functional recovery (LV developed pressure 12 +/- 4 vs. 9 +/- 2 mmHg in control-2, P = 0.5).

Conclusion

Ketamine can block the cardioprotective effects of ischemic preconditioning. This effect is caused by the R(-)-isomer.
Amitriptyline versus Bupivacaine in Rat Sciatic Nerve Blockade
Authors: Gerner Peter , Mujtaba Mustafa , Sinnott Catherine J. , Wang Ging Kuo
Published: November 2003

Background

Amitriptyline, a tricyclic antidepressant, is frequently used orally for the management of chronic pain. To date there is no report of amitriptyline producing peripheral nerve blockade. The authors therefore investigated the local anesthetic properties of amitriptyline in rats and in vitro.

Methods

Sciatic nerve blockade was performed with 0.2 ml amitriptyline or bupivacaine at selected concentrations, and the motor, proprioceptive, and nociceptive blockade was evaluated. Cultured rat GH3 cells were externally perfused with amitriptyline or bupivacaine, and the drug affinity toward inactivated and resting Na+ channels was assessed under whole-cell voltage clamp conditions. In addition, use-dependent blockade of these drugs at 5 Hz was evaluated.

Results

Complete sciatic nerve blockade for nociception was obtained with amitriptyline for 217 +/- 19 min (5 mM, n = 8, mean +/- SEM) and for 454 +/- 38 min (10 mM, n = 7) versus bupivacaine for 90 +/- 13 min (15.4 mM, n = 6). The time to full recovery of nociception for amitriptyline was 353 +/- 12 min (5 mM) and 656 +/- 27 min (10 mM) versus 155 +/- 9 min for bupivacaine (15.4 mM). Amitriptyline was approximately 4.7-10.6 times more potent than bupivacaine in binding to the resting channels (50% inhibitory concentration [IC50] of 39.8 +/- 2.7 vs. 189.6 +/- 22.3 microM) at - 150 mV, and to the inactivated Na+ channels (IC50 of 0.9 +/- 0.1 vs. 9.6 +/- 0.9 microM) at -60 mV. High-frequency stimulation at 3 microM caused an additional approximately 14% blockade for bupivacaine, but approximately 50% for amitriptyline.

Conclusion

Amitriptyline is a more potent blocker of neuronal Na+ channels than bupivacaine in vivo and in vitro. These findings suggest that amitriptyline could extend its clinical usefulness for peripheral nerve blockade.
Inhibitory Effects of Etomidate and Ketamine on Endothelium-dependent Relaxation in Canine Pulmonary Artery
Authors: Ogawa Koji , Tanaka Satoru , Murray Paul A.
Published: November 2003

Background

The authors recently demonstrated that acetylcholine-induced pulmonary vasorelaxation had two primary components, nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). The goal was to investigate the effects of etomidate and ketamine on the NO- and EDHF-mediated components of pulmonary vasorelaxation in response to acetylcholine, bradykinin, and the calcium ionophore, A23187.

Methods

Canine pulmonary arterial rings with an intact endothelium were suspended in organ chambers for isometric tension recording. The effects of etomidate and ketamine (10(-5) M and 10(-4) M) on vasorelaxation responses to acetylcholine, bradykinin, and A23187 were assessed in phenylephrine-contracted rings. The NO- and EDHF-mediated components of relaxation were assessed using a NO synthase inhibitor (N-nitro-L-arginine methylester [L-NAME]: 10(-4) M) and a Ca2+-activated potassium channel inhibitor (tetrabutylammonium hydrogen sulfate [TBA]: 10(-3) M) in rings pretreated with a cyclooxygenase inhibitor (ibuprofen: 10(-5) M). Intracellular calcium concentration ([Ca2+]i) was measured in cultured bovine pulmonary artery endothelial cells loaded with acetoxylmethyl ester of fura-2.

Results

Etomidate and ketamine attenuated pulmonary vasorelaxation in response to acetylcholine and bradykinin, whereas they had no effect on the response to A23187. The relaxant responses to acetylcholine and bradykinin were attenuated by L-NAME or TBA alone and were abolished by combined inhibition in rings pretreated with ibuprofen. Etomidate and ketamine further attenuated both L-NAME-resistant and TBA-resistant relaxation. These anesthetics also inhibited increases in endothelial [Ca2+]i in response to bradykinin, but not A23187.

Conclusion

These results indicate that etomidate and ketamine attenuated vasorelaxant responses to acetylcholine and bradykinin by inhibiting both NO- and EDHF-mediated components. Moreover, our results suggest that these anesthetics do not directly suppress NO or EDHF activity, but rather inhibit the endothelial [Ca2+]i transient in response to receptor activation.
Inhibitory Effects of Barbiturates on Nicotinic Acetylcholine Receptors in Rat Central Nervous System Neurons
Authors: Kamiya Yoshinori , Andoh Tomio , Watanabe Itaru , Higashi Tomoko , Itoh Hideki
Published: November 2003

Background

Neuronal nicotinic acetylcholine receptors (nAChRs) are widely expressed in the central and autonomic nervous systems. The authors have previously shown that depressant and convulsant barbiturates both inhibit the ganglion-type nAchRs in PC12 cells. However, the central and gangliontype receptors have different subunit composition and pharmacologic properties. In this study, the authors investigated the effects of thiopental, depressant [R(-)] and convulsant [S(+)] stereoisomers of 1-methyl-5 phenyl-5-propyl barbituric acid (MPPB) on neuronal nAChRs in the rat central nervous system to explore significance of these effects in barbiturate anesthesia.

Methods

Whole-cell currents were measured in acutely dissociated rat medial habenula (MHb) neurons by applying 10 or 100 microM nicotine in the absence or presence of thiopental 3-100 microM. Effects of R(-)- and S(+)-MPPB on the nicotine-induced current were also studied.

Results

Thiopental suppressed the nicotine-elicited inward current and accelerated the current decay dose-dependently at the clinical relevant concentrations. R(-)- and S(+)-MPPB both inhibited the nicotine-induced current dose-dependently without augmenting the current decay. There was no significant difference in the magnitudes of inhibition by R(-)- and S(+)-MPPB.

Conclusions

Although thiopental suppressed the current mediated through native nAchRs in rat MHb neurons at the clinically relevant concentrations, the depressant and convulsant stereoisomers of MPPB both inhibited the current in the same extent. These findings are consistent with the results previously obtained in the ganglion-type receptors of PC12 cells and suggest that inhibition of nAChRs in MHb neurons is not directly relevant to the hypnotic or anticonvulsive actions of barbiturates.
Electrocautery-induced Tachycardia in a Rate-responsive Pacemaker
Authors: Wong David T. , Middleton William
Published: November 2003

Electric interference by cautery on demand pacemakers can cause inhibition and loss of pacing. We report a case in which electrocautery induced a pacemaker in ventricle-paced, ventricle-sensed, inhibited, rate-responsive (VVIR) mode to pace at a programmed maximum rate of 130 pulses/min.
Dose-dependent Regional Cerebral Blood Flow Changes during Remifentanil Infusion in Humans
Authors: Wagner Klaus J. , Willoch Frode , Kochs Eberhard F. , Siessmeier Thomas , Tölle Thomas R. , Schwaiger Markus , Bartenstein Peter
Published: November 2003

Background

The current study investigated dose-dependent effects of the mu-selective agonist remifentanil on regional cerebral blood flow (rCBF) in volunteers using positron emission tomography (PET).

Methods

Ten right-handed male volunteers were included in a 15O-water PET study. Seven underwent three conditions: control (saline), low remifentanil (0.05 microg x kg(-1) x min(-1)), and moderate remifentanil (0.15 microg x kg(-1) x min(-1)). The remaining three participated in the low and moderate conditions. A semirandomized study protocol was used with control and remifentanil conditions 3 or more months apart. The order of low and moderate conditions was randomized. Cardiovascular and respiratory parameters were monitored. Categoric comparisons between the control, low, and moderate conditions and a pixelwise correlation analysis across the three conditions were performed (P < 0.05, corrected for multiple comparisons) using statistical parametric mapping.

Results

Cardiorespiratory parameters were maintained constant over time. At the low remifentanil dose, significant increases in relative rCBF were noted in the lateral prefrontal cortices, inferior parietal cortices, and supplementary motor area. Relative rCBF decreases were observed in the basal mediofrontal cortex, cerebellum, superior temporal lobe, and midbrain gray matter. Moderate doses further increased rCBF in mediofrontal and anterior cingulate cortices, occipital lobe transition, and caudal periventricular grey. Significant decreases were detected in the inferior parietal lobes. These dose-dependent effects of remifentanil on rCBF were confirmed by a correlation analysis.

Conclusion

Remifentanil induced dose-dependent changes in relative rCBF in areas involved in pain processing. At moderate doses, rCBF responses were additionally detected in structures known to participate in modulation of vigilance and alertness. Insight into the mechanisms of opioid analgesia within the pain-processing neural network may lead to a better understanding of antinociception and opioid treatment.
Dose–Response Relationship and Infusion Requirement of Cisatracurium Besylate in Infants and Children during Nitrous Oxide–Narcotic Anesthesia
Authors: de Ruiter Joost , Crawford Mark W.
Published: November 2003

Background

To determine the effect of age on the dose-response relation and infusion requirement of cisatracurium besylate in pediatric patients, 32 infants (mean age, 0.7 yr; range, 0.3-1.0 yr) and 32 children (mean age, 4.9 yr; range, 3.1-9.6 yr) were studied during thiopentone-nitrous oxideoxygen-narcotic anesthesia.

Methods

Potency was determined using a single-dose (20, 26, 33, or 40 microg/kg) technique. Neuromuscular block was assessed by monitoring the electromyographic response of the adductor pollicis to supramaximal train-of-four stimulation of the ulnar nerve at 2 Hz.

Results

Least-squares linear regression analysis of the log-probit transformation of dose and maximal response yielded median effective dose (ED50) and 95% effective dose (ED95) values for infants (29+/-3 microg/kg and 43+/-9 microg/kg, respectively) that were similar to those for children (29+/-2 microg/kg and 47+/-7 microg/kg, respectively). The mean infusion rate necessary to maintain 90-99% neuromuscular block during the first hour in infants (1.9+/-0.4 microg x kg(-1) x min(-1); range: 1.3-2.5 microg x kg(-1) x min(-1)) was similar to that in children (2.0+/-0.5 microg x kg(-1) x min(-1); range: 1.3-2.9 microg x kg(-1) x min(-1)).

Conclusion

The authors conclude that cisatracurium is equipotent in infants and children when dose is referenced to body weight during balanced anesthesia.
Epinephrine Increases the Neurotoxic Potential of Intrathecally Administered Lidocaine in the Rat
Authors: Hashimoto Keishi , Hampl Karl F. , Nakamura Yuji , Bollen Andrew W. , Feiner John , Drasner Kenneth
Published: November 2003

Background

Epinephrine is commonly added to lidocaine solutions to increase the duration of spinal anesthesia. Despite this common usage, the effect of epinephrine on the neurotoxic potential of this anesthetic is not known. The current experiments investigated whether adding epinephrine increases functional impairment or histologic damage induced by spinal administration of lidocaine in the rat.

Methods

Eighty rats were divided into four groups to receive an intrathecal injection of normal saline containing either 5% lidocaine, 5% lidocaine with 0.2 mg/ml of epinephrine, 0.2 mg/ml of epinephrine, or normal saline alone. Animals were assessed for persistent sensory impairment using the tail-flick test administered 4 and 7 days after infusion. Animals were then killed, and the spinal cord and nerve roots were prepared for neuropathologic evaluation.

Results

Rats given 5% lidocaine developed persistent sensory impairment and histologic damage, and the addition of epinephrine resulted in a further significant increase in injury. Sensory function in animals given epinephrine without anesthetic was similar to baseline and did not differ from saline. Histologic changes in animals treated with epinephrine alone did not differ significantly from saline controls.

Conclusions

The neurotoxicity of intrathecally administered lidocaine is increased by the addition of epinephrine. When making clinical recommendations for maximum safe intrathecal dose of this anesthetic, one may need to consider whether the solution contains epinephrine.
Propofol Alters the Pharmacokinetics of Alfentanil in Healthy Male Volunteers
Authors: Mertens Martijn J. , Vuyk Jaap , Olofsen Erik , Bovill James G. , Burm Anton G. L.
Published: November 2003

Background

The influence of propofol on the pharmacokinetics of alfentanil is poorly understood. The authors therefore studied the effect of a pseudo-steady state concentration of propofol on the pharmacokinetics of alfentanil.

Methods

The pharmacokinetics of alfentanil was studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week interval. While breathing 30% O2 in air, 12.5 microg/kg intravenous alfentanil was given in 2 min, followed by 25 microg.kg(-1).h(-1) for 58 min (sessions A and B). During session B, a target controlled infusion of propofol (target concentration, 1.5 microg/ml) was given from 10 min before the start until 6 h after termination of the alfentanil infusion. Blood pressure, cardiac output, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal carbon dioxide were monitored. Venous blood samples for determination of the plasma alfentanil concentration were collected until 6 h after termination of the alfentanil infusion. Nonlinear mixed-effects population pharmacokinetic models examining the influence of propofol and mean arterial pressure were constructed.

Results

A three-compartment model, including a lag time accounting for the venous blood sampling, adequately described the concentration-time curves of alfentanil Propofol decreased the elimination clearance of alfentanil by 15%, rapid distribution clearance by 68%, slow distribution clearance by 51%, and lag time by 62%. Mean arterial pressure and systemic vascular resistance were significantly lower in the presence of propofol. Scaling the pharmacokinetic parameters to the mean arterial pressure instead of propofol improved the model.

Conclusions

Propofol alters the pharmacokinetics of alfentanil. Hemodynamic changes induced by propofol may have an important influence on the pharmacokinetics of alfentanil.
The Neurologic and Adaptive Capacity Score Is Not a Reliable Method of Newborn Evaluation
Authors: Halpern Stephen H. , Littleford Judith A. , Brockhurst Nicole J. , Youngs Paul J. , Malik Nariman , Owen Holly C.
Published: November 2003

Background

The Neurologic and Adaptive Capacity Score (NACS) is a multi-item scale that was published in 1982 to measure the effects of intrapartum drugs on the neonate. Although this scoring system has been widely used in obstetric anesthesia research, studies confirming its reliability have not been published. The purpose of this study was to assess the reliability of the NACS.

Methods

Two teams of observers were trained to perform the NACS on healthy, term neonates born in the vertex presentation. Two examinations were performed on each neonate within the first 2.5 h of life. Simultaneous (or "split-half") reliability was assessed using the alpha coefficient. Test-retest reliability was assessed using the intraclass correlation coefficient. The test was considered to be reliable if a was greater than 0.7 and the intraclass correlation coefficient was greater than 0.6.

Results

Two hundred babies were studied. The a was 0.47 and the intraclass correlation coefficient was 0.38 (95% confidence interval, 0.24-0.52).

Conclusions

The NACS had poor reliability both on simultaneous testing and in the test-retest situation when used to evaluate term, healthy neonates. The authors suggest that other measures need to be developed to evaluate the effect of intrapartum drug administration in the neonate. Health measurement scales should undergo rigorous assessment for reliability and validity before they are used in clinical practice or for research purposes.
The Effect of Sevoflurane and Desflurane on Upper Airway Reactivity
Authors: Klock P. Allan , Czeslick Elke G. , Klafta Jerome M. , Ovassapian Andranik , Moss Jonathan
Published: November 2003

Background

Although bronchial reactivity can be assessed by changes in airway resistance, there is no well-accepted measure of upper airway reactivity during anesthesia. The authors used the stimulus of endotracheal tube cuff inflation and deflation to assess changes in airway reactivity in patients anesthetized with sevoflurane and desflurane.

Methods

Sixty-four patients classified as American Society of Anesthesiologists physical status I or II participated in this randomized, double-blind study. Patients were anesthetized with either sevoflurane or desflurane at 1.0 and 1.8 minimum alveolar concentration (MAC). The trachea was stimulated by inflating the endotracheal tube cuff. A blinded observer assessed the severity of patient response to the stimulus and changes in hemodynamic variables. The process was repeated at the second MAC treatment condition.

Results

At 1.0 MAC, patients anesthetized with desflurane had a more intense response and a greater likelihood of significant coughing and associated hemodynamic changes (both at P < 0.05). At 1.8 MAC, sevoflurane and desflurane both suppressed clinically significant responses to tracheal stimulation. Interrater reliability was excellent for this measure of upper airway reactivity (P < 0.001).

Conclusions

The assessment of the cough response to tracheal stimulation by endotracheal tube cuff inflation is a reliable and clinically meaningful measure of upper airway reactivity. At 1.0 MAC, sevoflurane is superior to desflurane for suppressing moderate and severe responses to this stimulus.
Comparison of the Intubating Laryngeal Mask Airway with the Fiberoptic Intubation in Anticipated Difficult Airway Management
Authors: Langeron Olivier , Semjen François , Bourgain Jean-Louis , Marsac Alain , Cros Anne-Marie
Published: November 2003

Background

The intubating laryngeal mask airway (ILMA; Fastrach; Laryngeal Mask Company, Henley-on-Thames, UK) may provide an alternative technique to fiberoptic intubation (FIB) to facilitate the management of the anticipated difficult airway. The authors therefore compared the effectiveness of the ILMA with FIB in patients with anticipated difficult intubation.

Methods

One hundred patients, with at least one difficult intubation criteria (Mallampati class III or IV, thyromental distance < 65 mm, interincisor distance < 35 mm) were enrolled (FIB group, n = 49; ILMA group, n = 51) in this prospective randomized study. Anesthesia was induced with propofol and maintained with alfentanil and propofol after an efficient mask ventilation has been demonstrated. The success of the technique (within three attempts), the number of attempts, duration of the successful attempt, and adverse events (oxygen saturation < 90%, bleeding) were recorded.

Results

The rate of successful tracheal intubation with ILMA was 94% and comparable with FIB (92%). The number of attempts and the time to succeed were not significantly different between groups. In case of failure of the first technique, the alternative technique always succeeded. Failures in FIB group were related to oxygen desaturation (oxygen saturation < 90%) and bleeding, and to previous cervical radiotherapy in the ILMA group. Adverse events occurred significantly more frequently in FIB group than in ILMA group (18 vs. 0%, P < 0.05).

Conclusion

The authors obtained a high success rate and comparable duration of tracheal intubation with ILMA and FIB techniques. In patients with previous cervical radiotherapy, the use of ILMA cannot be recommended. Nevertheless, the use of the ILMA was associated with fewer adverse events.
Subanesthetic Isoflurane Affects Task-induced Brain Activation in a Highly Specific Manner
Authors: Heinke Wolfgang , Schwarzbauer Christian
Published: November 2003

Background

Functional magnetic resonance imaging of blood oxygenation level-dependent signal changes offers a very promising approach to investigate activated neural networks during anesthesia.

Methods

Sixteen healthy male volunteers, assigned into two groups of eight subjects (isoflurane group, control group), were investigated by functional magnetic resonance imaging during different experimental conditions. The isoflurane group successively breathed air (baseline condition), isoflurane in air (0.42 vol% inspiratory; isoflurane condition) and air again (recovery condition) while performing a visual search task, whereas the control group breathed air during all experimental conditions. Functional magnetic resonance images were acquired during the entire experimental session. In addition, reaction times and error rates were recorded.

Results

A significant isoflurane-related decrease (z > 3.1 corresponding to P < 0.001) in task-induced brain activation was found in three distinct cortical regions: the right anterio-superior insula (Talairach coordinates: x = 32, y = 22, z = 8) and the banks of the left and right intraparietal sulcus (Talairach coordinates: x = -34, y = -36, z = 32; x = 22, y = -60, z = 41, respectively). Subcortical structures (lateral geniculate nucleus) and the primary cortices (motor cortex, visual cortex) were not affected. All measured parameters indicated a nearly complete recovery of the affected networks within 5 min.

Conclusions

Our findings indicate that subanesthetic isoflurane affected task-induced activation in specific neural networks rather than causing a global decrease in functional activation.
Lack of Degradation of Sevoflurane by a New Carbon Dioxide Absorbent in Humans
Authors: Mchaourab Ali , Arain Shahbaz R. , Ebert Thomas J.
Published: November 2003

Background

Potent inhaled anesthetics degrade in the presence of the strong bases (sodium hydroxide or potassium hydroxide) in carbon dioxide (CO2) absorbents. A new absorbent, Amsorb (Armstrong Medical Ltd., Coleraine, Northern Ireland), does not employ these strong bases. This study compared the scavenging efficacy and compound A production of two commercially available absorbents (soda lime and barium hydroxide lime) with Amsorb in humans undergoing general anesthesia.

Methods

Four healthy volunteers were anesthetized on different days with desflurane, sevoflurane, enflurane, and isoflurane. End-tidal carbon dioxide (ETCO2) and anesthetic concentrations were measured with infrared spectroscopy; blood pressure and arterial blood gases were obtained from a radial artery catheter. Each anesthetic exposure lasted 3 h, during which the three fresh (normally hydrated) CO2 absorbents were used for a period of 1 h each. Anesthesia was administered with a fresh gas flow rate of 2 l/min of air:oxygen (50:50). Tidal volume was 10 ml/kg; respiratory rate was 8 breaths/min. Arterial blood gases were obtained at baseline and after each hour. Inspired concentrations of compound A were measured after 15, 30, and 60 min of anesthetic administration for each CO2 absorbent.

Results

Arterial blood gases and ETCO2 were not different among three CO2 absorbents. During sevoflurane, compound A formed with barium hydroxide lime and soda lime, but not with Amsorb.

Conclusions

This new CO2 absorbent effectively scavenged CO2 and was not associated with compound A production.
Moderate Hypothermia Depresses Arterial Baroreflex Control of Heart Rate during, and Delays Its Recovery after, General Anesthesia in Humans
Authors: Tanaka Makoto , Nagasaki Go , Nishikawa Toshiaki
Published: November 2003

Background

Effects of hypothermia on arterial baroreflex function during, and on its recovery after, general anesthesia were examined in humans.

Methods

Twenty healthy volunteers were randomly assigned to a normothermic group (n = 10 each, active forced-air warming) or to a hypothermic group (no active warming) during anesthesia. Measurements of R-R intervals and systolic blood pressure were made at conscious baseline and at 20, 60, and 120 min after the induction and 20, 60, 120, and 180 min after emergence from general anesthesia with sevoflurane for 2 h. Ventilation was mechanically controlled, and end-tidal sevoflurane concentration was maintained at 2% during anesthesia. Baroreflex responses were triggered by bolus intravenous injections of phenylephrine and nitroprusside. The linear portions of the baroreflex curves relating R-R intervals and systolic blood pressure were determined to obtain baroslopes.

Results

During anesthesia, the mean lowest tympanic temperature of the hypothermia group (33.9+/-0.5 degrees C [mean +/- SD]) was significantly lower than that of the normothermia group (36.1+/-0.7 degrees C, P < 0.001). The baroslopes of the pressor and depressor tests were decreased by 19-39% during and by 27-53% after general anesthesia in the hypothermia group, compared with the normothermia group (P < 0.05). The baroslopes of the normothermia group returned to the baseline values at 60 min after anesthesia, whereas the pressor test sensitivity of the hypothermia group was significantly less than that of the normothermia group for the entire course of recovery.

Conclusions

The results indicate that moderate hypothermia enhances anesthesia-induced depression of baroreflex function in anesthetized humans and delays its recovery after general anesthesia.
Impact of Spinal Cord Stimulation on Sensory Characteristics in Complex Regional Pain Syndrome Type I
Authors: Kemler Marius A. , Reulen Jos P. H. , Barendse Gerard A. M. , van Kleef Maarten , de Vet Henrica C. W. , van den Wildenberg Frans A. J. M.
Published: November 2003

Background

A randomized trial was performed to assess the effect of spinal cord stimulation (SCS) on detection and pain thresholds for pressure, warmth, and cold and on the extent of mechanical hyperalgesia in patients with chronic complex regional pain syndrome type I.

Methods

Fifty-four chronic complex regional pain syndrome type I patients were randomized to receive both SCS and physical therapy (SCS+PT; n = 36), or to receive only physical therapy (PT; n = 18). Twenty-four SCS+PT patients responded positively to trial stimulation and underwent SCS implantation. During a 12-month follow-up period, six quantitative sensory testing sessions were performed. The main analysis compared 24 SCS patients with 29 nonimplanted patients--one PT patient was excluded.

Results

SCS showed no effect on detection thresholds for warmth and cold or on pain thresholds for any sensation. The pressure detection threshold initially increased by SCS, but after 3 months, pressure detection thresholds returned to normal. Mechanical hyperalgesia, both dynamic and static, was reduced slightly with SCS.

Conclusions

Although SCS has previously been shown to cause a significant pain reduction in complex regional pain syndrome type I, the treatment has no long-term effect on detection and pain thresholds for pressure, warmth, or cold. The treatment seems to have only minimal influence on mechanical hyperalgesia.
Pharmacokinetics of Bupivacaine after Continuous Epidural Infusion in Infants with and without Biliary Atresia
Authors: Meunier Jean-François , Goujard Etienne , Dubousset Anne-Marie , Samii Kamran , Xavier Mazoit Jean
Published: November 2003

Background

Continuous epidural infusion of bupivacaine is widely practiced for postoperative pain relief in pediatric patients. However, bupivacaine may induce adverse effects in infants (convulsions or cardiac arrhythmias), likely because of decreased hepatic clearance and serum protein binding capacity. The authors wanted to examine the complex relations between age, alpha-1 acid glycoprotein (AAG) concentration, and unbound and total bupivacaine serum concentrations in infants receiving bupivacaine epidurally for 2 days.

Methods

Twenty-two infants aged 1-7 months (12 with biliary atresia and 10 with another disease) received a continuous epidural infusion of 0.375 mg x kg(-1) x h(-1) bupivacaine during 2 days (during and after surgery). Unbound and total bupivacaine concentration in serum was measured 0.5, 4, 24, and 48 h after infusion initiation. AAG concentration was measured in serum before and 2 days after surgery. In eight additional infants, the blood/plasma concentration ratio was measured in vitro at whole blood concentrations of 2 and 20 microg/ml. Bupivacaine concentration was fitted to a one-compartment model to calculate basic pharmacokinetic parameters.

Results

No adverse effects were observed. AAG increased markedly after surgery, and the increase was correlated to both age and preoperative AAG concentration. Two infants aged 1.8 months had unbound concentrations greater than 0.2 microg/ml. Clearance of unbound drug significantly increased with age. Because of increased drug binding, clearance of bound drug decreased both with time (from 0.5 to 48 h) and with age. Blood/plasma ratio was 0.77+/-0.08 and 0.85+/-0.24 at 2 and 20 microg/ml, respectively.

Conclusions

Because of a low AAG concentration and a low intrinsic clearance, unbound bupivacaine increased to concentrations greater than 0.2 microg/ml in two infants younger than 2 months, after 2 days of infusion at a rate of 0.375 mg x kg(-1) x h(-1). The increase in AAG observed after surgery did not fully buffer this unbound fraction. Similarly, the buffer capacity of erythrocytes did not sufficiently increase at high concentration to compensate the saturation of the AAG system. Thus, we propose the use of a maximum dose of 0.25 mg x kg(-1) x h(-1) in infants younger than 4 months and a maximum of 0.3 mg x kg(-1) x h(-1) in infants older than 4 months.
Effects of Thoracic Epidural Anesthesia with and without Autonomic Nervous System Blockade on Cardiac Monophasic Action Potentials and Effective Refractoriness in Awake Dogs
Authors: Meissner Andreas , Eckardt Lars , Kirchhof Paulus , Weber Thomas , Rolf Norbert , Breithardt Günter , Van Aken Hugo , Haverkamp Wilhelm
Published: November 2003

Background

The effects of thoracic epidural anesthesia (TEA) on myocardial repolarization and arrhythmogenicity are only incompletely understood. This is primarily because of the lack of appropriate experimental models. In most of the studies performed thus far, TEA was used in anesthetized animals. Baseline anesthesia itself may have modified the effects of TEA. This study investigates right atrial and ventricular repolarization by recording monophasic action potentials after TEA in awake dogs. The authors hypothesized that an antiarrhythmic role of TEA exists, which may be related to a direct effect of TEA on myocardial repolarization.

Methods

The hypothesis was tested in an in vivo canine model, in which atrial and ventricular myocardial action potential duration and refractoriness are recorded by means of monophasic action potential catheters.

Results

Thoracic epidural anesthesia significantly increased ventricular monophasic action potential duration for cycle lengths shorter than 350 ms. Changes in monophasic action potential duration were paralleled by a concomitant prolongation of effective refractory period (ERP) at higher rates so that the ratio of ERP to action potential duration was unaffected.

Conclusions

This model helps to study the role of TEA on ventricular repolarization and arrhythmogenicity. Because lengthening of repolarization and prolongation of refractoriness may, in some circumstances, be antiarrhythmic, TEA may be protective against generation of ventricular arrhythmias mediated, e.g., by increased sympathetic tone. The results also imply that the beneficial role of TEA might be stronger at the ventricular site as compared with the atrium. At atrial sites there was only a trend toward prolongation of repolarization even at short cycle lengths.