bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative Anxiolysis and Postoperative Recovery in Women Undergoing Abdominal Hysterectomy
Authors: Kain Zeev N. , Sevarino Ferne B. , Rinder Christine , Pincus Sharon , Alexander Gerianne M. , Ivy Michael , Heninger George 
Published: November 2003

Background
Every year, millions of patients receive sedatives for reduction of anxiety before surgery, but there is little objective data on the effect of this treatment on postoperative outcomes. To address this issue, the effects of benzodiazepine administration were evaluated in women undergoing abdominal surgery.

Methods
Patients were randomized to receive 1 mg of oral lorazepam the night before surgery and 5 mg of intramuscular midazolam on the morning of surgery (n = 34), or to receive a placebo the night before surgery and on the morning of surgery (n = 36). Postoperative pain (Visual Analogue Scale for pain, McGill Pain Questionnaire) and analgesic consumption (patient-controlled analgesia), and clinical recovery parameters such as time to discharge from hospital were evaluated after surgery.

Results
Patient-controlled analgesia use showed a marginal main effect of treatment group (F(1,51) = 2.8; P = 0.047). Post boc analysis demonstrated that patient-controlled analgesia consumption was significantly lower in the treatment group only during the first 4 h of patient-controlled analgesia use after surgery (P = 0.027). There were no significant group differences at any later postoperative time points (P = not significant). There were no group differences in the cumulative Percocet (Pfizer, New York, NY) consumption in the postoperative period (P = not significant). Further, self-reported postoperative pain did not differ significantly between groups at any of the time points (P = not significant). There were also no group differences with regard to any postoperative clinical recovery parameters.

Conclusions
Benzodiazepines administered before surgery have minimal beneficial effects on the postoperative clinical course of women undergoing abdominal hysterectomy.
Physical Factors Affecting the Production of Carbon Monoxide from Anesthetic Breakdown
Authors: Woehlck Harvey J. , Dunning Marshall , Raza Tasleem , Ruiz Franklin , Bolla Bhupinder , Zink Wolfgang 
Published: November 2003

Background
Parameters determining carbon monoxide (CO) concentrations produced by anesthetic breakdown have not been adequately studied in clinical situations. The authors hypothesized that these data will identify modifiable risk factors.

Methods
Carbon monoxide concentrations were measured when partially desiccated barium hydroxide lime was reacted with isoflurane (1.5%) and desflurane (7.5%) in a Draeger Narkomed 2 anesthesia machine with a latex breathing bag substituting for a patient. Additional experiments determined the effects of carbon dioxide (0 or 350 ml/min), fresh gas flow rates (1 or 4 l/min), minute ventilation (6 or 18 l/min), or absorbent quantity (1 or 2 canisters). End-tidal anesthetic concentrations were adjusted according to a monochromatic infrared monitor.

Results
Desflurane produced approximately 20 times more CO than isoflurane when completely dried absorbents were used. Peak CO concentrations approached 100,000 ppm with desflurane. Traces of water remaining after a 66-h drying time (one weekend) markedly reduced the generation of CO compared with 2 weeks of drying. Reducing the quantity of desiccated absorbent by 50% reduced the total CO production by 40% in the first hour. Increasing the fresh gas flow rate from 1 to 4 l/min increased CO production by 67% in the first hour but simultaneously decreased average inspiratory concentrations by 53%. Carbon dioxide decreased CO production by 12% in completely desiccated absorbents.

Conclusion
Anesthetic identity, fresh gas flow rates, absorbent quantity, and water content are the most important factors determining patient exposures. Minute ventilation and carbon dioxide production by the patient are relatively unimportant.
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.