bluuebunny/crossref_metadata_2025 huggingface dataset:
Isoflurane and Sevoflurane Anesthesia in Pigs with a Preexistent Gas Exchange Defect
Authors: Kleinsasser Axel , Lindner Karl H. , Hoermann Christoph , Schaefer Andreas , Keller Christian , Loeckinger Alexander
Published: November 2003

Background

Decreased arterial partial pressure of oxygen (PaO2) during volatile anesthesia is well-known. Halothane has been examined with the multiple inert gas elimination technique and has been shown to alter the distribution of pulmonary blood flow and thus PaO2. The effects of isoflurane and sevoflurane on pulmonary gas exchange remain unknown. The authors hypothesized that sevoflurane with a relatively high minimum alveolar concentration (MAC) would result in significantly more gas exchange disturbances in comparison with isoflurane or control.

Methods

This study was performed in a porcine model with an air pneumoperitoneum that generates a reproducible gas exchange defect. After a baseline measurement of pulmonary gas exchange (multiple inert gas elimination technique) during propofol anesthesia, 21 pigs were randomly assigned to three groups of seven animals each. One group received isoflurane anesthesia, one group received sevoflurane anesthesia, and one group was continued on propofol anesthesia (control). After 30 min of volatile anesthesia at 1 MAC or propofol anesthesia, a second measurement (multiple inert gas elimination technique) was performed.

Results

At the second measurement, inert gas shunt was 15 +/- 3% (mean +/- SD) during sevoflurane anesthesia versus 9 +/- 1% during propofol anesthesia (P = 0.02). Blood flow to normal ventilation/perfusion (V(A)/Q) lung areas was 83 +/- 5% during sevoflurane anesthesia versus 89 +/- 1% during propofol anesthesia (P = 0.04). This resulted in a PaO2 of 88 +/- 11 mmHg during sevoflurane anesthesia versus 102 +/- 15 mmHg during propofol anesthesia (P = 0.04). Inert gas and blood gas variables during isoflurane anesthesia did not differ significantly from those obtained during propofol anesthesia.

Conclusions

In pigs with an already existent gas exchange defect, sevoflurane anesthesia but not isoflurane anesthesia causes significantly more gas exchange disturbances than propofol anesthesia does.
Unventilated Airway Is Time-dependently Constricted in Paralyzed Dogs
Authors: Hirota Kazuyoshi , Hashiba Eiji , Kabara Shizuko , Yoshioka Hideki , Ishihara Hironori , Matsuki Akitomo
Published: November 2003

Background

Apnea has been reported to produce bronchoconstriction and to cause hypoxia, hypercapnia, and modulation of vagal afferent nerves, which also change airway tone. In this study, the authors determined the mechanism of apnea-induced bronchoconstriction.

Methods

Twenty-eight dogs anesthetized and paralyzed were assigned to four groups (n = 7 each): apnea after artificial ventilation with 50% and 100% O2 groups (apnea-50% O2 and apnea-100% O2 groups, respectively), an apnea plus vagotomy group (fraction of inspired oxygen [FiO2] = 1.0), and a one-lung ventilation group (FiO2 = 1.0). The trachea was intubated with a single- or double-lumen tube in the three apnea groups or the one-lung ventilation group, respectively. The bronchial cross-sectional area (BCA) was assessed by the authors' bronchoscopic method. In the apnea-100% O2 and apnea plus vagotomy groups, a respirator was turned off for 5 min to produce apnea. In the apnea-50% O2 group, apnea was produced for 3 min. In the one-lung ventilation group, the right lumen was blocked for 5 min, and 15 min later, the left lumen was blocked for 5 min. BCA, arterial oxygen tension (PaO2), and arterial carbon dioxide tension (PaCO2) were assessed every minute.

Results

The BCA in intact dogs time-dependently decreased by approximately 20% and 40% at 3 and 5 min after apnea started, respectively, whereas they did not in vagotomized dogs. In the apnea-50% O2 and apnea-100% O2 groups, bronchoconstriction could occur without hypoxemia, although hypercapnia was observed in all dogs. In the one-lung ventilation group, despite the fact that PaCO2 increased by only 2 mmHg without hypoxemia, unventilated BCA time-dependently decreased by 33.6 +/- 10.3%, whereas ventilated BCA did not.

Conclusion

The current study suggests that the unventilated airway may constrict spontaneously. In addition, the airway constriction could be vagally mediated but not due to hypoxia and hypercapnia.
Cardiopulmonary Bypass Induces Neurologic and Neurocognitive Dysfunction in the Rat
Authors: Mackensen G. Burkhard , Sato Yukie , Nellgård Bengt , Pineda Jose , Newman Mark F. , Warner David S. , Grocott Hilary P.
Published: November 2003

Background

Neurocognitive dysfunction is a common complication of cardiac surgery using cardiopulmonary bypass (CPB). Elucidating injury mechanisms and developing neuroprotective strategies have been hampered by the lack of a suitable long-term recovery model of CPB. The purpose of this study was to investigate neurologic and neurocognitive outcome after CPB in a recovery model of CPB in the rat.

Methods

Fasted rats (n = 10) were subjected to 60 min of normothermic (37.5 degrees C) nonpulsatile CPB using a roller pump and a membrane oxygenator. Sham-operated controls (n = 10) were not subjected to CPB. Neurologic outcome was assessed on days 1, 3, and 12 after CPB using standardized functional testing. Neurocognitive outcome, defined as the time (or latency) to finding a submerged platform in a Morris water maze (an indicator of visual-spatial learning and memory), was evaluated daily from post-CPB days 3-12. Histologic injury in the hippocampus was also evaluated.

Results

Neurologic outcome was worse in the CPB versus the sham-operated controls at all three measurement intervals (P < 0.001). The CPB group also had longer water maze latencies compared with the sham-operated controls (P = 0.004), indicating significant neurocognitive dysfunction after CPB. No difference in histologic injury between groups was observed.

Conclusions

CPB caused both neurologic and neurocognitive impairment in a rodent recovery model. This model could potentially facilitate the investigation of CPB-related injury mechanisms and possible neuroprotective interventions.
The Effectiveness of Video Technology As an Adjunct to Teach and Evaluate Epidural Anesthesia Performance Skills
Authors: Birnbach David J. , Santos Alan C. , Bourlier Remi A. , Meadows Warner E. , Datta Sanjay , Stein Deborah J. , Kuroda Maxine M. , Thys Daniel M.
Published: November 2003

Background

Although video review has been used in teaching, it has not been reported for use as an adjunct to teaching anesthesiology residents. The purpose of the prospective, randomized, blinded study was to determine whether teaching with video review improves epidural anesthesia skills of anesthesiology residents.

Methods

Twenty-two second-year (CA-2) anesthesiology residents beginning their first obstetric anesthesia rotation were assigned to video or non-video groups. All residents were filmed daily as they placed epidural analgesia. Residents assigned to the video group reviewed their tapes twice a week with an attending anesthesiologist, whereas residents assigned to the non-video group never saw their films. Four experienced attending anesthesiologists independently judged videotapes taken on days 1, 15, and 30 and scored the residents for "overall" skill (range of summed overall grades, 0-40), as well as on 13 predetermined criteria.

Results

As determined by kappa coefficients, interrater reliability was high among the judges (k = 0.7-0.8). Residents in the video group improved to a greater degree than residents in the non-video group. On day 1, the median overall grades for the video and non-video groups were 21 and 12, respectively. By day 15, the corresponding grades had increased to 32 and 24, respectively (P < 0.01). However, overall median grades continued to improve between days 15 and 30 in the video group only (P < 0.01).

Conclusions

Review of resident videotapes resulted in greater improvement in overall and predetermined performance criteria. In addition, video review was helpful in identifying skills that were inadequately learned, thus allowing for specific teaching in those areas.
Simulation Technology
Authors: Morgan Pamela J. , Cleave-Hogg Doreen , McIlroy Jodi , Devitt James Hugh
Published: November 2003

Background

The availability of simulator technology at the University of Toronto (Toronto, Ontario, Canada) provided the opportunity to compare the efficacy of video-assisted and simulator-assisted learning.

Methods

After ethics approval from the University of Toronto, all final-year medical students were invited to participate in the current randomized trial comparing video-based to simulator-based education using three scenarios. After an introduction to the simulator environment, a 5-min performance-based pretest was administered in the simulator operating room requiring management of a critical event. A posttest was administered after students had participated in either a faculty-facilitated video or simulator teaching session. Standardized 12-point checklist performance protocols were used for assessment purposes. As well, students answered focused questions related to the educational sessions on a final examination. Student opinions regarding the value of the teaching sessions were obtained.

Results

One hundred forty-four medical students participated in the study (scenario 1, n = 43; scenario 2, n = 48; scenario 3, n = 53). There was a significant improvement in posttest scores over pretest scores in all scenarios. There was no statistically significant difference in scores between simulator or video teaching methods. There were no differences in final examination marks when the two educational methods were compared. Student opinions indicated that the experiential simulator sessions were more enjoyable and valuable than the video teaching sessions.

Conclusions

Both simulator and video types of faculty-facilitated education offer a valuable learning experience. Future work is needed that addresses the long-term effects of experiential learning in the retention of knowledge and acquired skills.
Phase I Safety Assessment of Intrathecal Injection of an American Formulation of Adenosine in Humans
Authors: Eisenach James C. , Hood David D. , Curry Regina
Published: November 2003

Background

Preclinical studies of intrathecal adenosine suggest it may be effective in the treatment of acute and chronic pain in humans. A phase I safety trial of the intrathecal injection of a mannitol-containing formulation of adenosine in Sweden showed a considerable incidence of backache. We performed a phase I safety trial of intrathecal injection of the American formulation of adenosine, which lacks mannitol.

Methods

Following US Food and Drug Administration and institutional review board approval and written informed consent, 65 volunteers were studied in two trials: an open-label, dose-escalating trial with intrathecal adenosine doses of 0.25-2.0 mg (25 subjects) and a double-blind, placebo-controlled trial of adenosine, 2 mg (40 subjects). Blood pressure, heart rate, end-tidal carbon dioxide, and sensory, motor, and reflex neurologic functions were systematically examined for 24 h after injection, and volunteers were contacted by telephone at times up to 6 months after injection.

Results

Intrathecal adenosine did not affect blood pressure, heart rate, end-tidal carbon dioxide, or neurologic function. Headache was reported by 10 and back pain was reported by 8 of 30 subjects exposed to adenosine in the second double-blind trial, whereas none of these symptoms was reported by the 10 saline-treated subjects.

Conclusion

These data support further investigation of intrathecal adenosine for analgesia in humans and suggest that this agent does not produce a high incidence of severe side effects.
Preliminary Efficacy Assessment of Intrathecal Injection of an American Formulation of Adenosine in Humans
Authors: Eisenach James C. , Hood David D. , Curry Regina
Published: November 2003

Background

Preclinical studies of intrathecal adenosine suggest it may be effective in the treatment of acute and chronic pain in humans, and preliminary studies in volunteers and patients with a Swedish formulation of adenosine suggests it may be effective in hypersensitivity states but not with acute noxious stimulation. The purpose of this study was to screen for efficacy of a different formulation of adenosine marketed in the US, using both acute noxious stimulation and capsaicin-evoked mechanical hypersensitivity.

Methods

Following Food and Drug Administration and institutional review board approval and written informed consent, 65 volunteers were studied in two trials: an open-label, dose-escalating trial with intrathecal adenosine doses of 0.25-2.0 mg and a double-blind, placebo-controlled trial of adenosine, 2 mg. Cerebrospinal fluid was obtained for pharmacokinetic analysis, and pain ratings in response to acute heat stimuli and areas of mechanical hyperalgesia and allodynia after intradermal capsaicin injection were determined.

Results

Adenosine produced no effect on pain report to acute noxious thermal or chemical stimulation but reduced mechanical hyperalgesia and allodynia from intradermal capsaicin injection for at least 24 h. In contrast, residence time of adenosine in cerebrospinal fluid was short (< 4 h).

Conclusions

These results show selective inhibition by intrathecal adenosine of hypersensitivity, presumed to reflect central sensitization in humans after peripheral capsaicin injection. The long-lasting effect is consistent with that observed in preliminary reports of patients with chronic neuropathic pain and is not due to prolonged residence of adenosine in cerebrospinal fluid.
Nasotracheal Intubation
Authors: Elwood Tom , Stillions Duane M. , Woo Dawn W. , Bradford Heidi M. , Ramamoorthy Chandra
Published: November 2003

Background

Several techniques have been suggested to reduce the trauma of nasotracheal intubation, although no comparative studies exist. The authors evaluated red-rubber catheters as a guide to nasotracheal intubation.

Methods

Children presenting for elective surgery were randomized to undergo red-rubber catheter-guided nasotracheal intubation or to have the nasotracheal tube alone inserted. After general anesthesia and paralysis with vecuronium, the nares were prepared with topical vasoconstrictor. The nasotracheal tube was softened with warm water. In the catheter-guided group, the nasotracheal tube tip was fitted to the trailing end of the red-rubber catheter, and the two were advanced together. The red-rubber catheter was retrieved from the nasopharynx, disconnected, and removed. In the other group, the nasotracheal tube was advanced blindly into the nasopharynx. In both groups, intubation was then completed during direct laryngoscopy using Magill forceps. A blinded observer swabbed the pharynx and rated the severity of bleeding based on reference photographs.

Results

Age, weight, snoring history, and difficulty of intubation were not different between groups. Obvious bleeding was lower using the red-rubber catheter technique (10 vs. 29%, P = 0.013), which took longer to perform (74 vs. 56 s, P = 0.02).

Conclusions

Although the incidence of bleeding in both groups was similar, severity of bleeding was reduced in the catheter-guided group during nasotracheal intubation. Use of a red-rubber catheter may reduce the trauma associated with nasotracheal intubation.
Intracarotid Nitroprusside Does Not Augment Cerebral Blood Flow in Human Subjects
Authors: Joshi Shailendra , Young William L. , Duong Huang , Aagaard Beverly A. , Ostapkovich Noeleen D. , Connolly E. Sander , Pile-Spellman John
Published: November 2003

Background

The recent resurgence of interest in the cerebrovascular effects of nitroprusside can be attributed to the possibility of using nitric oxide donors in treating cerebrovascular insufficiency. However, limited human data suggest that intracarotid nitroprusside does not directly affect cerebrovascular resistance. In previous studies, physiologic or pharmacologic reactivity of the preparation was not tested at the time of nitroprusside challenge. The authors hypothesized that if nitric oxide is a potent modulator of human cerebral blood flow (CBF), then intracarotid infusion of nitroprusside will augment CBF.

Methods

Cerebral blood flow was measured (intraarterial (133)Xe technique) in sedated human subjects undergoing cerebral angiography during sequential infusions of (1) intracarotid saline, (2) intravenous phenylephrine to induce systemic hypertension, (3) intravenous phenylephrine with intracarotid nitroprusside (0.5 microg x kg(-1) x min(-1)), and (4) intracarotid verapamil (0.013 mg x kg(-1) x min(-1)). Data (mean +/- SD) were analyzed by repeated-measures analysis of variance and post hoc Bonferroni-Dunn test.

Results

Intravenous phenylephrine increased systemic mean arterial pressure (from 83 +/- 12 to 98 +/- 6 mmHg; n = 8; P < 0.001), and concurrent infusion of intravenous phenylephrine and intracarotid nitroprusside reversed this effect. However, compared with baseline, CBF did not change with intravenous phenylephrine or with concurrent infusions of intravenous phenylephrine and intracarotid nitroprusside. Intracarotid verapamil increased CBF (43 +/- 9 to 65 +/- 11 ml x 100 g(-1) x min(-1); P < 0.05).

Conclusions

The authors conclude that, in humans, intracarotid nitroprusside sufficient to decrease mean arterial pressure during recirculation, does not augment CBF. Failure of intracarotid nitroprusside to augment CBF despite demonstrable autoregulatory vasoconstriction and pharmacologic vasodilation questions the significance of nitric oxide-mediated vasodilation in human cerebral circulation.
Continuous Positive Airway Pressure in New-generation Mechanical Ventilators
Authors: Takeuchi Muneyuki , Williams Purris , Hess Dean , Kacmarek Robert M.
Published: November 2003

Background

A number of new microprocessor-controlled mechanical ventilators have become available over the last few years. However, the ability of these ventilators to provide continuous positive airway pressure without imposing or performing work has never been evaluated.

Methods

In a spontaneously breathing lung model, the authors evaluated the Bear 1000, Drager Evita 4, Hamilton Galileo, Nellcor-Puritan-Bennett 740 and 840, Siemens Servo 300A, and Bird Products Tbird AVS at 10 cm H(2)O continuous positive airway pressure. Lung model compliance was 50 ml/cm H(2)O with a resistance of 8.2 cm H(2)O x l(-1) x s(-1), and inspiratory time was set at 1.0 s with peak inspiratory flows of 40, 60, and 80 l/min. In ventilators with both pressure and flow triggering, the response of each was evaluated.

Results

With all ventilators, peak inspiratory flow, lung model tidal volume, and range of pressure change (below baseline to above baseline) increased as peak flow increased. Inspiratory trigger delay time, inspiratory cycle delay time, expiratory pressure time product, and total area of pressure change were not affected by peak flow, whereas pressure change to trigger inspiration, inspiratory pressure time product, and trigger pressure time product were affected by peak flow on some ventilators. There were significant differences among ventilators on all variables evaluated, but there was little difference between pressure and flow triggering in most variables on individual ventilators except for pressure to trigger. Pressure to trigger was 3.74 +/- 1.89 cm H(2)O (mean +/- SD) in flow triggering and 4.48 +/- 1.67 cm H(2)O in pressure triggering (P < 0.01) across all ventilators.

Conclusions

Most ventilators evaluated only imposed a small effort to trigger, but most also provided low-level pressure support and imposed an expiratory workload. Pressure triggering during continuous positive airway pressure does require a slightly greater pressure than flow triggering.
Economic Evaluation of Propofol for Sedation of Patients Admitted to Intensive Care Units
Authors: Anis Aslam H. , Wang Xiao-hua , Leon Hector , Hall Richard
Published: November 2003

Background

The goal of the current study was to evaluate the economic impact of propofol as compared with midazolam for sedating patients in the intensive care unit (ICU).

Methods

A randomized, unblinded, multicenter pharmacoeconomic trial captured health resource utilization and outcome measurements associated with sedation and treatment of patients in four ICUs across Canada. Statistical analysis was performed to investigate the difference in sedation quality, ICU length of stay, and other health resources used. The authors compared the costs (1997 Canadian dollars) associated with the two treatments. Two types of sensitivity analyses were performed.

Results

Although overall sedation duration was similar, propofol patients spent more time at adequately sedated status (60.2% vs. 44%; P = 0.01) and were extubated faster (median extubation time, 2.5 vs. 7.1 h; P = 0.001). The ICU length of stay and health resource utilization did not differ. The total cost per patient, including drug cost and ICU stay cost, did not differ between groups (median, $5,718 for propofol vs. $5,950 for midazolam; P = 0.94). The first sensitivity analysis suggested that the incremental cost (per patient) of propofol varies from an extra cost of $114 to a savings of $2,709. Based on a hypothetical model, the second sensitivity analysis showed a potential saving of $479 per patient as a result of improved discharge planning.

Conclusion

The analysis demonstrated that using propofol resulted in a reduction of time to extubation and higher sedative regimen costs. There was no difference in intensity of resource use or ICU length of stay and hence in costs. Issues regarding discharge delay among propofol-treated patients remain to be explored.
Absence of Beneficial Effect of Acute Normovolemic Hemodilution Combined with Aprotinin on Allogeneic Blood Transfusion Requirements in Cardiac Surgery
Authors: Höhn Laurent , Schweizer Alexandre , Licker Marc , Morel Denis R.
Published: November 2003

Background

The efficacy of acute normovolemic hemodilution (ANH) in decreasing allogeneic blood requirements remains controversial during cardiac surgery.

Methods

In a prospective, randomized study, 80 adult cardiac surgical patients with normal cardiac function and no high risk of ischemic complications were subjected either to ANH, from a mean hematocrit of 43% to 28%, or to a control group. Aprotinin and intraoperative blood cell salvage were used in both groups. Blood (autologous or allogeneic) was transfused when the hematocrit was less than 17% during cardiopulmonary bypass, less than 25% after cardiopulmonary bypass, or whenever clinically indicated.

Results

The amount of whole blood collected during ANH ranged from 10 to 40% of the patients' estimated blood volume. Intraoperative and postoperative blood losses were not different between control and ANH patients (total blood loss, control: 1,411 +/- 570 ml, n = 41; ANH: 1,326 +/- 509 ml, n = 36). Allogeneic blood was given in 29% of control patients (median, 2; range, 1-3 units of packed erythrocytes) and in 33% of ANH patients (median, 2; range, 1-5 units of packed erythrocytes; P = 0.219). Preoperative and postoperative platelet count, prothrombin time, and partial thromboplastin time were similar between groups. Perioperative morbidity and mortality were not different in both groups, and similar hematocrit values were observed at hospital discharge (33.7 +/- 3.9% in the control group and 32.6 +/- 3.7% in the ANH group; nonsignificant)

Conclusions

Hemodilution is not an effective means to lower the risk of allogeneic blood transfusion in elective cardiac surgical patients with normal cardiac function and in the absence of high risk for coronary ischemia, provided standard intraoperative cell saving and high-dose aprotinin are used.
Electroacupuncture Prophylaxis of Postoperative Nausea and Vomiting following Pediatric Tonsillectomy with or without Adenoidectomy
Authors: Rusy Lynn M. , Hoffman George M. , Weisman Steven J.
Published: November 2003

Background

Electrical stimulation of acupuncture point P6 reduces the incidence of postoperative nausea or vomiting (PONV) in adult patients. However, acupressure, laser stimulation of P6, and acupuncture during anesthesia have not been effective for reducing PONV in the pediatric population. The authors studied the effect of electrical P6 acupuncture in awake pediatric patients who had undergone surgery associated with a high incidence of PONV.

Methods

Patients aged 4-18 yr undergoing tonsillectomy with or without adenoidectomy were randomly assigned to acupuncture, sham acupuncture, or control groups. Acupuncture needles at P6 and a neutral point were placed while patients were anesthetized, and low-frequency electrical stimulation was applied to these points for 20 min in the recovery room while the patients were awake (P6 Acu group). This treatment was compared with sham needles along the arm at acupuncture points not associated with antiemesis (sham group) and a no-needle control group. The arms were wrapped to prevent identification of treatment group, and anesthetic, analgesic, and surgical technique were standardized. Assessed outcomes were occurrence of nausea, occurrence and number of episodes of vomiting, time to vomiting, and use of antiemetic rescue medication.

Results

One hundred twenty patients were enrolled in the study, 40 per group. There were no differences in age, weight, sex, or opioid administration between groups. The PONV incidence was significantly lower with P6 acupuncture (25 of 40 or 63%; odds ratio, 0.135; number needed to treat, 3.3; P < 0.001) compared with controls (37 of 40 or 93%). Sham puncture had no effect on PONV (35 of 40 or 88%; P = not significant). Occurrence of nausea was significantly less in P6 Acu (24 of 40 or 60%; odds ratio, 0.121; P < 0.01), but not in the sham group (34 of 40 or 85%) compared with the control group (37 of 40 or 93%). Vomiting occurred in 25 of 40 or 63% in P6 Acu; 35 of 40 or 88% in the sham group, and 31 in 40 or 78% in the control group (P = not significant). Patients receiving sham puncture vomited significantly earlier (P < 0.02) and needed more rescue treatment (33 of 40 or 83%; odds ratio, 3.48; P < 0.02) compared with P6 Acu (23 of 40 or 58%) and the control group (24 of 40 or 60%).

Conclusions

Perioperative P6 electroacupuncture in awake patients significantly reduced the occurrence of nausea compared with the sham and control groups, but it did not significantly reduce the incidence or number of episodes of emesis or the use of rescue antiemetics. Sham acupuncture may exacerbate the severity but not the incidence of emesis. The efficacy of P6 acupuncture for PONV prevention is similar to commonly used pharmacotherapies. Its appropriate role in prevention and treatment of PONV requires further study.
Can Assessment for Obstructive Sleep Apnea Help Predict Postadenotonsillectomy Respiratory Complications?
Authors: Wilson Kerryn , Lakheeram Indrani , Morielli Angie , Brouillette Robert , Brown Karen
Published: November 2003

Background

The aim of this study was to determine the frequency and type of respiratory complications after adenotonsillectomy in children. A second aim was to assess the ability of preoperative sleep studies to identify children at risk for respiratory complications.

Methods

Children referred for sleep studies between 1992 and 1998, who underwent adenotonsillectomy within 6 months of the preoperative study, were reviewed. The study focused on two variables: the obstructive apnea and hypopnea index and the oxygen saturation nadir. Medical charts were reviewed for postoperative respiratory complications.

Results

Three hundred forty-nine children were referred for sleep studies, and 163 met the inclusion criteria. Thirty-four children (21%) had postoperative respiratory complications requiring a medical intervention. Children experiencing respiratory complications were younger (aged < 2 yr; adjusted odds ratio, 4.3; 95% confidence interval, 1.7-11) and had an associated medical condition (odds ratio, 3; 95% confidence interval, 1.4-6.5). A preoperative obstructive apnea and hypopnea index of 5 or more events per hour increased the chance of postoperative respiratory complications (odds ratio, 7.2; 95% confidence interval, 2.7-19.3), as did a preoperative oxygen saturation nadir of 80% or less (odds ratio, 6.4; 95% confidence interval, 2.8-14.5). A preoperative oxygen saturation nadir of 80% or less had a likelihood ratio of 3.1, increasing the probability of postoperative respiratory complications from 20 to 50%.

Conclusions

The data suggest, but do not prove, that preoperative nocturnal oximetry could be a useful preoperative test to identify children who are at increased risk for postoperative respiratory complications.
Effect of the α2-Agonist Dexmedetomidine on Cerebral Neurotransmitter Concentrations during Cerebral Ischemia in Rats
Authors: Engelhard Kristin , Werner Christian , Kaspar Susanne , Möllenberg Oliver , Blobner Manfred , Bachl Monika , Kochs Eberhard
Published: November 2003

Background

This study investigates whether neuroprotection seen with dexmedetomidine is associated with suppression of peripheral or central sympathetic tone.

Methods

Thirty fasted male Sprague-Dawley rats were intubated and ventilated with isoflurane and N2O/O2 (fraction of inspired oxygen = 0.33). Catheters were inserted into the right femoral artery and vein and into the right jugular vein. Cerebral blood flow was measured using laser Doppler flowmetry. Bilateral microdialysis probes were placed into the cortex and the dorsal hippocampus. At the end of preparation, the administration of isoflurane was replaced by fentanyl (bolus: 10 microg/kg; infusion: 25 microg x kg(-1) x h(-1)). Animals were randomly assigned to one of the following groups: group 1 (n = 10): control animals; group 2 (n = 10): 100 microg/kg dexmedetomidine administered intraperitoneally 30 min before ischemia; group 3 (n = 10): sham-operated rats. Ischemia (30 min) was produced by unilateral carotid artery occlusion plus hemorrhagic hypotension to a mean arterial blood pressure of 30-35 mmHg to reduce ipsilateral cerebral blood flow by 70%. Pericranial temperature, arterial blood gases, and pH were maintained constant. Cerebral catecholamine and glutamate concentrations and plasma catecholamine concentrations were analyzed using high-performance liquid chromatography.

Results

During ischemia, dexmedetomidine suppressed circulating norepinephrine concentrations by 95% compared with control animals. In contrast, brain norepinephrine and glutamate concentrations were increased irrespective of dexmedetomidine infusion before ischemia.

Conclusions

The current data show that the increase of circulating catecholamine concentrations during cerebral ischemia was suppressed with dexmedetomidine. In contrast, dexmedetomidine does not suppress elevation in brain norepinephrine and glutamate concentration associated with cerebral ischemia. This suggests that the neuroprotective effects of dexmedetomidine are not related to inhibition of presynaptic norepinephrine or glutamate release in the brain.
Recombinant Human Transgenic Antithrombin in Cardiac Surgery
Authors: Levy Jerrold H. , Despotis George J. , Szlam Fania , Olson Peter , Meeker David , Weisinger Andrew
Published: November 2003

Background

Acquired antithrombin III (AT) deficiency may render heparin less effective during cardiac surgery and cardiopulmonary bypass (CPB). The authors examined the pharmacodynamics and optimal dose of recombinant human AT (rh-AT) needed to maintain normal AT activity during CPB, optimize the anticoagulant response to heparin, and attenuate excessive activation of the hemostatic system in patients undergoing coronary artery bypass grafting.

Methods

Thirty-six patients scheduled to undergo elective primary coronary artery bypass grafting and who had received heparin for 12 h or more before surgery were enrolled in the study. Ten cohorts of three patients each received rh-AT in doses of 10, 25, 50, 75, 100, 125, 175, or 200 U/kg, a cohort of six patients received 150 U/kg of rh-AT, and a control group of six patients received placebo.

Results

Antithrombin III activity exceeded 600 U/dl before CPB at the highest dose (200 U/kg). Doses of 75 U/kg rh-AT normalized AT activity to 100 U/dl during CPB. Activated clotting times during CPB were significantly (P < 0.0001) greater in patients who received rh-AT (844 +/- 191 s) compared with placebo patients (531 +/- 180 s). Significant (P = 0.001) inverse relations were observed between rh-AT dose and both fibrin monomer (r = -0.51) and D-dimer (r = -0.51) concentrations. No appreciable adverse events were observed with any rh-AT doses used in the study.

Conclusions

Supplementation of native AT with transgenically produced protein (rh-AT) in cardiac surgical patients was well tolerated and resulted in higher activated clotting times during CPB and decreased levels of fibrin monomer and D-dimer.
Utility of Whole Blood Hemostatometry Using the Clot Signature Analyzer®for Assessment of Hemostasis in Cardiac Surgery
Authors: Faraday Nauder , Guallar Eliseo , Sera Valerie A. , Bolton Everlie D. , Scharpf Robert B. , Cartarius Ann M. , Emery Kathryn , Concord Julia , Kickler Thomas S.
Published: November 2003

Background

A hemostatic monitor capable of rapid, accurate detection of clinical coagulopathy within the operating room could improve management of bleeding after cardiopulmonary bypass (CPB). The Clot Signature Analyzer is a hemostatometer that measures global hemostasis in whole blood. The authors hypothesized that point-of-care hemostatometry could detect a clinical coagulopathic state in cardiac surgical patients.

Methods

Fifty-seven adult patients scheduled for a variety of elective cardiac surgical procedures were studied. Anesthesia, CPB, heparin anticoagulation, protamine reversal, and transfusion for post-CPB bleeding were all managed by standardized protocol. Clinical coagulopathy was defined by the need for platelet or fresh frozen plasma transfusion. The Clot Signature Analyzer collagen-induced thrombus formation (CITF) assay measured platelet-mediated hemostasis in vitro. The activated clotting time, platelet count, prothrombin time, activated partial thromboplastin time, and fibrinogen concentration were also measured.

Results

The postprotamine CITF was greater in patients who required hemostatic transfusion than in those who did not (17.6 +/- 8.0 min vs. 10.5 +/- 5.7 min, respectively; P < 0.01). Postprotamine CITF values were highly correlated with platelet and fresh frozen plasma transfusion (Spearman r = 0.50, P < 0.001 and r = 0.40, P < 0.005, respectively). Receiver operator characteristic curves showed a highly significant relation between the postprotamine CITF and intraoperative platelet and fresh frozen plasma transfusion (area under the curve, 0.78-0.81, P < 0.005) with 60-80% sensitivity, specificity, positive and negative predictive values at cutoffs of 12-14 min. Logistic regression demonstrated that the CITF was independently predictive of post-CPB hemostatic transfusion, but standard hemostatic assays were not.

Conclusions

The Clot Signature Analyzer CITF detects a clinical coagulopathic state after CPB and is independently predictive of the need for hemostatic transfusion. Hemostatometry has potential utility for monitoring hemostasis in cardiac surgery.
Ketamine Suppresses Platelet Aggregation Possibly by Suppressed Inositol Triphosphate Formation and Subsequent Suppression of Cytosolic Calcium Increase
Authors: Nakagawa Takefumi , Hirakata Hideo , Sato Masami , Nakamura Kumi , Hatano Yoshio , Nakamura Takashi , Fukuda Kazuhiko
Published: November 2003

Background

Ketamine has been shown to suppress platelet aggregation, but its mechanisms of action have not been defined. The purpose of the current study is to clarify the effects of ketamine on human platelet aggregation and to elucidate the underlying mechanisms of its action.

Methods

Platelet aggregation was measured using an eight-channel aggregometer, and cytosolic free calcium concentration was measured in Fura-2/AM-loaded platelets using a fluorometer. Inositol 1,4,5-triphosphate (IP3) was measured with use of a commercially available IP3 assay kit. To estimate thromboxane A2 (TXA2) receptor binding affinity and expression, Scatchard analysis was performed using [3H]S145, a specific TXA2 receptor antagonist. TXA2 agonist binding assay was also performed. The membrane-bound guanosine 5'-triphosphatase activity was determined using [gamma-32P]guanosine triphosphate by liquid scintillation analyzer.

Results

Ketamine (500 microm) suppressed aggregation induced by adenosine diphosphate (0.5 microm), epinephrine (1 microm), (+)-9,11-epithia-11,12-methano-TXA2 (STA2) (0.5 microm), and thrombin (0.02 U/ml) to 39.1 +/- 30.9, 46.3 +/- 4.3, -2.0 +/- 16.8, and 86.6 +/- 1.4% of zero-control, respectively. Ketamine (250 microm-1 mm) also suppressed thrombin- and STA2-induced cytosolic free calcium concentration increase dose dependently. Although ketamine (2 mm) had no effect on TXA2 receptor expression and its binding affinity, it (1 mm) suppressed intracellular peak IP3 concentrations induced by thrombin and STA2 from 6.60 +/- 1.82 and 4.39 +/- 2.41 to 2.41 +/- 0.98 and 1.90 +/- 0.86 pmol/109 platelets, respectively, and it suppressed guanosine triphosphate hydrolysis induced by thrombin (0.02 units/ml) and STA2 (0.5 microm) to 50.3 +/- 3.2 and 67.5 +/- 5.5% versus zero-control, respectively.

Conclusion

Ketamine inhibits human platelet aggregation possibly by suppressed IP3 formation and subsequent suppression of cytosolic free calcium concentration. The site of action of ketamine is neither TXA2 nor thrombin binding sites but possibly receptor-coupled mechanisms, including G-protein.
Role of the Rostral Medial Medulla in the Development of Primary and Secondary Hyperalgesia after Incision in the Rat
Authors: Bosnjak Zeljko J. , Pogatzki Esther M. , Urban Mark O. , Brennan Timothy J. , Gebhart Gerald F.
Published: November 2003

Background

Descending influences from the rostral medial medulla (RMM) contribute to secondary hyperalgesia in persistent inflammatory, neuropathic, and visceral pain models. The current study examined if descending inhibition or facilitation from the RMM modulates primary and secondary hyperalgesia after incision in the rat hind limb.

Methods

Bilateral RMM lesions were produced using the soma-selective neurotoxin ibotenic acid, and the effect of RMM lesion was examined on primary and secondary hyperalgesia 5 days after a plantar or gastrocnemius incision, respectively.

Results

Plantar incision reduced withdrawal thresholds to von Frey filaments applied adjacent to the incision (primary punctate hyperalgesia). The withdrawal thresholds were the same in RMM-lesioned and sham-operated rats. The response frequency to a blunt mechanical stimulus after plantar incision was increased (primary nonpunctate hyperalgesia) in both groups. Nonpunctate hyperalgesia was greater in lesioned rats on postoperative day 2 only; all other measures were not different. Primary heat hyperalgesia after plantar incision was not modulated by RMM lesion. Secondary punctate hyperalgesia after gastrocnemius incision was not affected by RMM lesion. Gastrocnemius incision did not produce secondary nonpunctate or heat hyperalgesia in either RMM lesion or sham rats.

Conclusion

Primary and secondary hyperalgesia after an incision were not modulated by descending influence from the RMM. The lack of contribution of descending facilitatory influences from the RMM to secondary hyperalgesia after gastrocnemius incision supports the notion that incision-induced pain involves dissimilar mechanisms compared with inflammatory and neuropathic pain.
Thiopental Inhibits the Activation of Nuclear Factor κB
Authors: Loop Torsten , Liu Zhiheng , Humar Matjaz , Hoetzel Alexander , Benzing Albert , Pahl Heike L. , Geiger Klaus K. , J. Pannen Benedikt H.
Published: November 2003

Background

Thiopental is frequently used for the treatment of intracranial hypertension after severe head injury. Its long-term administration increases the incidence of nosocomial infections, which contributes to the high mortality rate of these patients. However, the mechanism of its immunosuppressing effect remains unknown.

Methods

The effect of thiopental (200-1000 microg/ml) on the activation of the nuclear transcription factor kappaB (NF-kappaB; electrophoretic mobility shift assays), on NF-kappaB-driven reporter gene activity (transient transfection assays), on the expression of NF-kappaB target genes (enzyme-linked immunoassays), on T-cell activation (flow cytometric analyses of CD69 expression), and on the content of the NF-kappaB inhibitor IkappaB-alpha (Western blotting) was studied in human T lymphocytes in vitro.

Results

Thiopental inhibited the activation of the transcription factor NF-kappaB but did not alter the activity of the cyclic adenosine monophosphate response element binding protein. Other barbiturates (methohexital), anesthetics (etomidate, propofol, ketamine), or opioids (fentanyl, morphine) did not affect NF-kappaB activation. Thiopental-mediated suppression of NF-kappaB could be observed in Jurkat cells and in primary CD3+ lymphocytes from healthy volunteers, was time- and concentration-dependent, occurred at concentrations that are clinically achieved, and persisted for hours after the incubation. It was associated with an inhibition of NF-kappaB-driven reporter gene activity, of the expression of interleukin-2, -6, and -8, and interferon gamma, and of the activation of CD3+ lymphocytes. Suppression of NF-kappaB appeared to involve reduced degradation of IkappaB-alpha.

Conclusion

The results demonstrate that thiopental inhibits the activation of NF-kappaB and may thus provide a molecular mechanism for some of the immunosuppressing effects associated with thiopental therapy.
Comparison of Electrophysiologic Effects of Propofol and Isoflurane-based Anesthetics in Children Undergoing Radiofrequency Catheter Ablation for Supraventricular Tachycardia
Authors: Erb Thomas O. , Kanter Ronald J. , Hall Janet M. , Gan Tong J. , Kern Frank H. , Schulman Scott R.
Published: November 2003

Background

Radiofrequency catheter ablation (RFCA), which is typically performed with general anesthesia in children, is an interventional therapy for tachyarrhythmia. Although the electrophysiologic (EP) effects of isoflurane- and propofol-based anesthetics have been shown to be similar, a retrospective analysis reported significantly longer RFCA procedural duration with the use of isoflurane. It remains unclear whether the ability to successfully perform RFCA differs between these drugs.

Methods

Patients were randomly assigned to receive either an isoflurane- or propofol-maintained anesthetic. Drug administration was titrated according to the pharmacodynamic endpoint of depth of sedation using bispectral index score. The ability to induce sustained tachycardia (using a scoring system), procedural durations, and effects on cardiac electrophysiologic properties were evaluated and compared between the groups.

Results

Sixty subjects were included in this study. Sustained supraventricular tachycardia (SVT) was inducible with the assigned drug in all but four subjects. In three of these four subjects, SVT was also not inducible with the alternative study drug. Ability to induce the first sustained SVT was similar between the groups (P = 0.83). Total procedural durations were similar (isoflurane 224 +/- 84 min vs. propofol 221 +/- 86 min, mean +/- SD, P = 0.88). Atrioventricular nodal conduction was slower with propofol compared with isoflurane, but this result did not appear to be clinically relevant. Finally, ventricular repolarization was prolonged by isoflurane versus propofol, the clinical significance of which was not demonstrated.

Conclusion

Isoflurane- and propofol-based anesthesia were equally suitable in children and adolescents undergoing RFCA.
Clinically Relevant Concentrations of Propofol Have No Effect on Adenosine Triphosphate–sensitive Potassium Channels in Rat Ventricular Myocytes
Authors: Kawano Takashi , Oshita Shuzo , Tsutsumi Yasuo , Tomiyama Yoshinobu , Kitahata Hiroshi , Kuroda Yasuhiro , Takahashi Akira , Nakaya Yutaka
Published: November 2003

Background

Activation of adenosine triphosphate-sensitive potassium (K(ATP)) channels produces cardioprotective effects during ischemia. Because propofol is often used in patients who have coronary artery disease undergoing a wide variety of surgical procedures, it is important to evaluate the direct effects of propofol on K(ATP) channel activities in ventricular myocardium during ischemia.

Methods

The effects of propofol (0.4-60.1 microg/ml) on both sarcolemmal and mitochondrial K(ATP) channel activities were investigated in single, quiescent rat ventricular myocytes. Membrane currents were recorded using cell-attached and inside-out patch clamp configurations. Flavoprotein fluorescence was measured to evaluate mitochondrial oxidation mediated by mitochondrial K(ATP) channels.

Results

In the cell-attached configuration, open probability of K(ATP) channels was reduced by propofol in a concentration-dependent manner (EC(50) = 14.2 microg/ml). In the inside-out configurations, propofol inhibited K(ATP) channel activities without changing the single-channel conductance (EC(50) = 11.4 microg/ml). Propofol reduced mitochondrial oxidation in a concentration-dependent manner with an EC(50) of 14.6 microg/ml.

Conclusions

Propofol had no effect on the sarcolemmal K(ATP) channel activities in patch clamp configurations and the mitochondrial flavoprotein fluorescence induced by diazoxide at clinically relevant concentrations (< 2 microm), whereas it significantly inhibited both K(ATP) channel activities at very high, nonclinical concentrations (> 5.6 microg/ml; 31 microm).
Isoflurane Pretreatment Inhibits Cytokine-induced Cell Death in Cultured Rat Smooth Muscle Cells and Human Endothelial Cells
Authors: de Klaver Manuela J. M. , Manning Lee , Palmer Lisa A. , Rich George F.
Published: November 2003

Background

Anesthetics are protective during ischemic-reperfusion injury and associated inflammation; therefore, the authors hypothesized that anesthetic pretreatment may provide protection in culture from cytokine-induced cell death.

Methods

Rat vascular smooth muscle (VSM) cell and human umbilical vascular endothelial cell (HUVEC) cultures were used to determine whether pretreatment with 30 min of isoflurane decreases cell death from tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1 beta), and interferon (IFN-gamma) alone or in combination. Cell survival and viability were determined by trypan blue staining and cell proliferation assay, as well as by DNA fragmentation assays. The roles of protein kinase C (PKC) and adenosine triphosphate-sensitive potassium (K(ATP)) channels in mediating isoflurane (and halothane) protection were evaluated with the antagonists staurosporine or glibenclamide in cytokine- and also hydrogen peroxide (H(2)O(2))-induced cell death.

Results

Pretreatment with 1.5% isoflurane immediately prior to cytokine exposure increased cell survival and viability from cytokines by 10-60% for 24, 48, 72, and 96 h in VSMs and up to 72 h in HUVECs. DNA fragmentation (TUNEL) was also attenuated by isoflurane. Isoflurane was equally effective in VSMs at 0.75, 1.5, and 2.5%, whereas in HUVECs, 1.5 and 2.5% were more effective than 0.75%. In VSMs, isoflurane administered 1 h prior to or simultaneously with cytokines was also effective, whereas isoflurane 2 h prior to cytokines was less effective, and either 4 h prior to or 30 min after cytokines was not effective. In both cytokine- and H(2)O(2)-induced cell death, isoflurane and halothane pretreatment were equally protective, and staurosporine and glibenclamide attenuated the protective effect.

Conclusions

Thirty minutes of isoflurane attenuates cytokine-induced cell death and increases cell viability in VSMs for 96 h and in HUVECs for 72 h. Isoflurane must be administered less than 2 h prior to or simultaneously with the cytokines to be protective. These initial inhibitor studies suggest involvement of PKC and K(ATP) channels in isoflurane and halothane protection against both cytokine- and H(2)O(2)-induced cell death of VSMs and HUVECs.