bluuebunny/crossref_metadata_2025 huggingface dataset:
Rate of Coronary Flow Adaptation in Response to Changes in Heart Rate before and during Anesthesia for Coronary Artery Surgery
Authors: van Wezel Harry B. , Kal Jasper E. , Vergroesen Isabelle , Vroom Margreeth B. , De Graaf Ruud , Dankelman Jenny , Porsius Marjolein , Spaan Jos A. E.
Published: November 2003

Background

The rate of adaptation of coronary blood flow in response to stepwise changes in heart rate (HR) has been extensively studied in dogs and goats to improve our understanding of the dynamics of coronary regulation processes and their pathophysiology and to obtain time constants for mathematical modeling of the coronary regulation. However, little is known about the dynamic characteristics of coronary flow adaptation in humans. In patients undergoing coronary artery surgery, we investigated the rate of coronary adaptation in response to stepwise changes in HR, in the awake and anesthetized states.

Methods

In 11 patients with stable coronary artery disease, arterial blood pressure, right atrial pressure, and coronary sinus blood flow, measured by continuous thermodilution, were calculated per beat. The ratio of beat-averaged arterial blood pressure minus right atrial pressure and coronary sinus blood flow was calculated to obtain an index of coronary resistance. The rate of change of coronary resistance index was quantified by t50, defined as the time required to establish 50% of the total change in coronary resistance index. Responses of coronary resistance index after HR changes, before and after induction of anesthesia, were compared. The anesthesia technique consisted of 100 micrograms.kg-1 fentanyl and 0.1 mg.kg-1 pancuronium bromide in combination with oxygen in air ventilation (FIO2 = 0.5).

Results

In the awake situation, t50 values of the dilating and constricting responses, induced by an increase and a decrease in HR were 5.0 +/- 2.1 (SD) s (range 2.6-9.0 s) and 5.7 +/- 1.2 s (range 4.1-7.8 s), respectively. During fentanyl/pancuronium anesthesia, the rate of coronary flow adaptation was significantly slower, with t50 values of 10.2 +/- 2.1 s (range 7.7-13.1 s) after an HR step-up and 9.8 +/- 2.1 s (range 6.6-13.2 s) after an HR step-down. Compared to the awake situation, arterial blood pressure was significantly reduced during anesthesia, but coronary vascular resistance remained unchanged. This implies that the steady-state static regulation of coronary blood flow had not changed.

Conclusions

These preliminary data suggest that, in patients with coronary artery disease, the rate of change in coronary vascular resistance in response to pacing-induced changes in HR is mitigated by fentanyl/pancuronium anesthesia during positive pressure ventilation. A further qualification of our findings in a larger number of patients is warranted.
Pentobarbital Enhances Cyclic Adenosine Monophosphate Production in the Brain by Effects on Neurons but Not Glia
Authors: Gonzales Jerry M. , Mendez-Bobe Iris
Published: November 2003

Background

Cyclic adenosine monophosphate (cAMP) is an important regulator of neuronal excitability. The effects of barbiturates on cAMP production in intact neurons are not known. This study used cultures of cortical neurons, cultures of glia, and slices of cerebral cortex from the rat to study the effects of barbiturates on cAMP regulation in the brain.

Methods

Primary cultures of cortical neurons or glia were prepared from 17-day gestational Sprague-Dawley rat fetuses and were used after 12-16 days in culture. Cross-cut slices (300 microns) were prepared from cerebral cortex of adult rats. Cyclic AMP accumulation was determined by measuring the conversion of [3H]adenosine triphosphate (ATP) to [3H]cAMP in cells preloaded with [3H]adenine.

Results

Pentobarbital enhanced isoproterenol- and forskolin-stimulated, but not basal, cAMP accumulation in cultures of cerebral neurons. Cyclic AMP production was enhanced by pentobarbital in a dose-dependent fashion up to a concentration of 250 microM; This concentration of pentobarbital increased cAMP production by 40-50% relative to that in controls without pentobarbital. At 500 microM pentobarbital, the magnitude of the enhancement was less. Pentobarbital had no effect on isoproterenol-stimulated cAMP production in cultures containing only glia. Pentobarbital also enhanced isoproterenol-stimulated, but not basal, cAMP production in slices of cerebral cortex by approximately 30% at concentrations of 62.5-250 microM and by almost 100% at 500 microM.

Conclusions

Pentobarbital enhances stimulated cAMP accumulation in cultured preparations from brain and fresh cortical slices. Neurons are required for this effect. Because cAMP modulates neuronal excitability, this effect of pentobarbital may be an important mechanism by which this anesthetic influences brain function.
Volatile Anesthetics Selectively Inhibit the Calcium sup 2+ -transporting ATPase in Neuronal and Erythrocyte Plasma Membranes
Authors: Fomitcheva Ioulia , Kosk-Kosicka Danuta
Published: November 2003

Background

The activity of the plasma membrane Ca(2+)-transporting adenosine triphosphatase (PMCA) is inhibited by volatile anesthetics at clinical concentrations. The goal of the current study was to determine whether the inhibition is selective as compared to other adenosine triphosphatases (ATPases) and another group of general anesthetics, barbiturates. In addition, the authors determined whether the response to anesthetics of the enzymes in neuronal membranes is similar to that in erythrocyte membranes.

Methods

The effects of halothane, isoflurane, and sodium pentobarbital on four different ATPase activities were studied at 37 degrees C in two distinct plasma membrane preparations, human red blood cells and synaptosomal membranes from rat cerebellum.

Results

Inhibition patterns of the PMCA by halothane and isoflurane at anesthetic concentrations were vary similar in red blood cells and synaptosomal membranes. The half-maximal inhibition (I50) occurred at 0.25-0.30 mM halothane and 0.30-0.32 mM isoflurane. The PMCA in both membranes was significantly more sensitive to the inhibitory action of volatile anesthetics (I50 = 0.75-1.15 minimum alveolar concentration) than were other ATPases, such as the Na+,K+-ATPase (I50 approximately 3 minimum alveolar concentration) or Mg(2+)-ATPase (I50 > or = 5 minimum alveolar concentration). In contrast, sodium pentobarbital inhibited the PMCA in both membranes only at approximately 100-200-fold above its anesthetic concentrations. The other ATPases were inhibited at similar pentobarbital concentrations (I50 = 11-22 mM).

Conclusions

The findings demonstrate analogous response of the PMCA of neuronal and erythrocyte cells to two groups of general anesthetics. The PMCA activity is selectively inhibited by volatile anesthetics at their clinical concentrations. The enzyme in vivo may then be a pharmacologic target for volatile anesthetics but not for barbiturates.
Effects of the Serotonin2Receptor Agonist DOI on Skeletal Muscle Specimens from Malignant Hyperthermia-susceptible Patients
Authors: Wappler Frank , Roewer Norbert , Kochling Andreas , Scholz Jens , Loscher Wolfgang , Steinfath Markus , Schulte am Esch Jochen
Published: November 2003

Background

Administration of serotonin2 (5-HT2) receptor agonists in pigs triggers malignant hyperthermia (MH) and psychotic-like behavior. Both can be reduced by 5-HT2 receptor antagonists. Furthermore, an increase in the plasma concentration of 5-HT has been found during onset of halothane-induced MH in pigs. Therefore, in this study, the in vitro effects of the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) were investigated in muscle specimens from MH-susceptible (MHS) and -negative (MHN) patients.

Methods

After MH classification using the caffeine-halothane contracture test (CHCT), surplus muscle specimens from 23 MHS and 17 MHN patients were used to examine the effects of DOI. In the first study, DOI was added to the bath in a concentration of 0.02 mM. In a second experiment, muscles were preincubated for 60 min with 0.02 mM DOI, and subsequently, halothane was added incrementally to the organ bath (0.11-0.22-0.44 mM) for 15 min according to the CHCT protocol. The in vitro effects of DOI on contracture development and muscle twitch were measured for 120 min in both investigations.

Results

Muscle specimens form all patients developed contractures after administration of DOI, characterized by a significantly earlier development of contracture in MHS (16.8 +/- 1.7 min) than in MHN (66.3 +/- 5.8 min) muscles (P < 0.05). There was no overlap between the groups in the range of times. The onset of contracture development after DOI was prolonged by halothane in specimens from MHN patients (89.7 +/- 5.6 min) but not MHS patients. Preincubation with DOI increased the halothane-induced contractures in specimens from MHS patients compared to the results of the CHCT. The contracture development in specimens from MHS patients was larger than from MHN patients. At the end of the experiment, contractures had reached a maximum of 12.9 +/- 1.1 mN in specimens from MHS and 5.3 +/- 0.6 mN in MHN patients (P < 0.05). The additional administration of halothane led to significantly increased contractures in specimens from MHS individuals (15.9 +/- 0.9 mN) at 120 min. However, the contracture development decreased significantly to 3.1 +/- 0.4 mN in MHN muscles. Muscle twitch after DOI administration was reduced significantly in specimens from MHS and MHN patients.

Conclusions

A functional or structural altered serotonin system might be involved in the development of MH in humans.
Normothemic Continuous Blood Cardioplegia Improves Electrophysiologic Recovery after Open Heart Surgery
Authors: Gozal Yaacov , Glantz Lucio , Luria Myron H. , Milgalter Eli , Shimon Dov , Drenger Benjamin
Published: November 2003

Background

Myocardial protection during open heart surgery is based on administration of oxygenated blood cardioplegia, the preferred temperature of which is still under debate. The current randomized study was designed to prospectively evaluate the quality of myocardial protection and the functional recovery of the heart with either normothermic (group N) or hypothermic (group H) oxygenated blood cardioplegia.

Methods

Under continuous electrocardiographic Holter monitoring, 42 patients were randomly scheduled to receive either normothermic (33.5 degrees C) or hypothermic (10 degrees C) cardioplegia solutions during coronary bypass grafting surgery. Blood samples for creatinine phosphokinase, creatinine phosphokinase-MB, lactate, epinephrine, and norepinephrine were withdrawn during cardiopulmonary bypass via a coronary sinus cannula.

Results

Active cooling in group H on initiation of cardiopulmonary bypass was characterized by transition through ventricular fibrillation in 75% of patients, whereas in group N atrial fibrillation occurred in 65% of patients. On myocardial reperfusion, sinus rhythm spontaneously resumed in 95% of group N patients compared to 25% in group H (P = 0.0003). In the latter, 75% of patients developed ventricular fibrillation often followed by complete atrioventricular block, which necessitated temporary pacing for a mean duration of 168 +/- 32 min. Both groups showed a similar incidence of intraventricular block and ST segment changes. However, the incidence of ventricular premature beats in the first 16 h after cardiopulmonary bypass was significantly greater in group H (P < 0.05), 20 +/- 26/h, compared to 3 +/- 5/h in group N. Blood concentrations of lactate, creatinine phosphokinase, epinephrine, and norepinephrine increased gradually during the operation, but the differences between the groups were not significant.

Conclusions

The current prospective human study suggests that the increased susceptibility for ventricular fibrillation and dysrhythmia, and the delayed recovery of the conduction system after hypothermic myocardial protection, are related to temperature-induced changes in vital cellular functions of the conduction tissue in the postischemic period. Both cardioplegic methods provide adequate myocardial protection but normothermic oxygenated blood cardioplegia may accelerate recovery of the heart after cardiopulmonary bypass.
Prospective Study of the Incidence of Transient Radicular Irritation in Patients Undergoing Spinal Anesthesia
Authors: Pollock Julia E. , Neal Joseph M. , Stephenson Carol A. , Wiley Carol E.
Published: November 2003

Background

There is considerable controversy regarding the role of subarachnoid 5% hyperbaric lidocaine in the syndrome transient radicular irritation (TRI). This randomized, double-blinded, prospective study was designed to determine the incidence of TRI and identify factors possibly contributing to its development.

Methods

One hundred fifty-nine ASA physical status 1 or 2 patients undergoing outpatient knee arthroscopy or unilateral inguinal hernia repair were prospectively randomized to receive spinal anesthesia with 5% hyperbaric lidocaine with epinephrine (60 mg with 0.2 mg epinephrine for arthroscopy or 75 mg with 0.2 mg epinephrine for hernia repair), 2% isobaric lidocaine without epinephrine (60 mg for arthroscopy or 75 mg for hernia repair), or 0.75% hyperbaric bupivacaine without epinephrine (7.5 mg for arthroscopy or 9.0 mg for hernia repair) in a double-blinded fashion. On the 3rd postoperative day, patients were contacted by a blinded investigator and questioned regarding the incidence of postoperative complications including TRI, defined as back pain with radiation down one or both buttocks or legs occurring within 24 h after surgery. Postoperatively, time from injection to block resolution, ambulation, voiding, and ready for discharge were recorded by a postanesthesia care unit nurse blinded to the group assignment.

Results

The incidence of TRI was greater in patients receiving lidocaine than in those receiving bupivacaine (16% vs. 0%; P = 0.003). There was no difference in the incidence of TRI between the patients receiving 5% hyperbaric lidocaine with epinephrine and those receiving 2% isobaric lidocaine without epinephrine (16% vs. 16%; P = 0.98). The incidence of TRI was greater in patients undergoing arthroscopy than in those undergoing hernia repair (13% vs. 5%; P = 0.04). There was no difference in discharge times in patients receiving bupivacaine versus those receiving hyperbaric lidocaine with epinephrine (292 vs. 322 min; P = 0.61).

Conclusions

The incidence of TRI is greater with lidocaine than bupivacaine, decreasing the lidocaine concentration to 2% does not prevent TRI, and surgical position may be an important contributing factor. Discharge times at our institution are not different when equipotent doses of 0.75% hyperbaric bupivacaine or 5% hyperbaric lidocaine with 0.2 mg epinephrine are used in ambulatory patients undergoing spinal anesthesia.
Dantrolene Sodium Can Increase or Attenuate Activity of Skeletal Muscle Ryanodine Receptor Calcium Release Channel
Authors: Nelson Thomas E. , Lin Marina , Zapata-Sudo Gisele , Sudo Roberto Takashi
Published: November 2003

Background

Dantrolene sodium (DS) is a direct-acting skeletal muscle relaxant whose only known action is to block calcium release from intracellular storage sites. The exact site of action for DS is unknown, but its efficacy in treating and preventing anesthetic-induced malignant hyperthermia (MH) is well established.

Methods

Single ryanodine (Ry1) receptor calcium release channels were incorporated into a planar lipid bilayer for electrophysiologic recording and for subsequent analysis of the channel's gating and conductance properties. The cellular effects of low DS concentrations were investigated by isometric contracture tension responses in biopsied MH human and dog muscle fascicles and in normal, single fibers from human vastus lateralis muscle.

Results

Two concentration-dependent DS effects on the isolated Ry1 receptor were discovered, suggesting at least two different binding sites. At nanomolar concentrations, DS activated the channel by causing three-to fivefold increases in open-state probability and dwell times. At micromolar concentrations, DS first increased then reduced activity in the channels; with the dominant effect being reduced activity. A 20 nm concentration of DS produced significant contracture tension in human muscle from one MH subject and caused potentiation of twitch in muscle from another MH patient. Halothane contracture in MH dog muscle was followed by an additional increase in tension when treated with 20 nm DS. Other investigations on chemically skinned, human fibers showed that calcium loaded in the sarcoplasmic reticulum was partially released by nM DS.

Conclusions

The study results suggest that at least two binding sites for DS exist on the Ry1 receptor calcium channel. A low-affinity (microM) site is associated with reduced channel gating and open-state dwell time and may relate to the established pharmacologic muscle relaxant effect of DS. The proposed high-affinity (nM) DS binding site activates the channel, producing Ca2+ release to the myoplasm, which, under environmentally adverse conditions, could damage genetically predisposed MH muscle. Such a phenomenon, if it occurs in DS treated MH patients, could generate a recrudescence of the syndrome.
Chlorocresol, an Additive to Commercial Succinylcholine, Induces Contracture of Human Malignant Hyperthermia-susceptible Muscles Via Activation of the Ryanodine Receptor Calcium sup 2+ Channel
Authors: Tegazzin Vincenzo , Scutari Erica , Treves Susan , Zorzato Francesco
Published: November 2003

Background

A defect in the ryanodine (Ry1) receptor Ca2+ channel has been implicated as one of the possible underlying causes of malignant hyperthermia (MH), a pharmacogenetic disorder characterized by sustained muscle contracture. The disease is triggered by common halogenated anesthetics and skeletal muscle relaxants, such as succinylcholine. This study tested whether the functional properties of the Ry1 receptor Ca2+ channel are affected by chlorocresol, a preservative added to a commercial preparation of succinylcholine (Midarine) and other parenteral compounds.

Methods

In vitro contracture testing was carried out on muscle biopsies from malignant hyperthermia-susceptible (MHS) and -negative (MHN) individual according to the protocol of the European MH group. Ca2+ flux studies on isolated rabbit sarcoplasmic reticulum fractions were measured spectrophotometrically by following the A710-790 of the Ca2+ indicator antipyrylazo III.

Results

Chlorocresol causes muscle contracture in MHS muscles at a concentration of 25-50 microM and potentiates the caffeine contracture response in human MHS muscles. Sub-threshold (20 microM) concentrations of chlorocresol increase both the Kd and the Vmax of caffeine-induced Ca2+ release from isolated rabbit terminal cisternae.

Conclusions

These data suggest that, in muscle from MHS individuals, the enhanced Ca2+ released from the sarcoplasmic reticulum may not be due to the effect of succinylcholine alone but rather to the action of the preservative chlorocresol added to the drug.
Acute Lung Injury after Instillation of Human Breast Milk or Infant Formula into Rabbits' Lungs
Authors: O'Hare Brendan , Lerman Jerrold , Endo Junko , Cutz Ernest
Published: November 2003

Background

Recent interest in shortening the fasting interval after ingestion of milk products demonstrated large volumes of breast milk in the stomach 2 h after breastfeeding. Although aspiration is a rare event, if it were to occur with human breast milk, it is important to understand the extent of the lung injury that might occur. Therefore, the response to instillation of acidified breast milk and infant formula in the lungs of adult rabbits was studied.

Methods

In 18 anesthetized adult rabbits, 1 of 3 fluids (in a volume of 0.8 ml.kg-1 and pH level of 1.8, acidified with hydrochloric acid); saline, breast milk, or infant formula (SMA, Wyeth, Windsor, Ontario), was instilled into the lungs via a tracheotomy. The lungs were ventilated for 4 h after instillation. Alveolar-to-arterial oxygen gradient and dynamic compliance were measured before and at hourly intervals after instillation. After 4 h, the rabbits were killed and the lungs were excised. Neutrophil infiltration was quantitated by a pathologist blinded to the instilled fluid. A histologic control group of four rabbits was ventilated under study conditions without any intratracheal fluid instillation.

Results

Alveolar-to-arterial oxygen gradient increased and dynamic compliance decreased significantly during the 4 h after instillation of both breast milk and infant formula compared with baseline measurements and with saline controls (P < 0.05). The neutrophil counts in the lungs from the saline, breast milk, and formula rabbits were significantly greater than those in the control group.

Conclusions

Instillation of acidified breast milk or infant formula (in a volume of 0.8 ml.kg-1 and pH level of 1.8) into rabbits' lungs induces acute lung injury of similar intensity that lasts at least 4 h.
Synaptic Mechanisms of Thiopental-induced Alterations in Synchronized Cortical Activity
Authors: Lukatch Heath S. , MacIver Bruce M.
Published: November 2003

Background

Anesthetic depth after barbiturate administration has been correlated with distinct electroencephalogram (EEG) patterns. The current study used a rat neocortical brain slice micro-EEG preparation to investigate synaptic mechanisms underlying thiopental-induced transitions in synchronized neuronal activity.

Methods

Concentration-dependent cellular actions of thiopental were investigated in brain slices using specific pharmacologic probes, whole cell patch clamps, and extracellular field recordings. Theta-Like micro-EEG oscillations were elicited in neocortical slices by mimicking subcortical cholinergic and gamma-aminobutyric acid (GABA) afferent input with carbachol (100 microM), a cholinergic agonist, and bicuculline (10 microM) a GABAA antagonist.

Results

In the presence of 20 microM thiopental, micro-EEG slowing from theta (7.3 +/- 0.9 Hz, mean +/- SD, n = 19) to delta frequencies (2.5 +/- 0.5 Hz, n = 11) was associated with a threefold prolongation of inhibitory currents. Burst suppression activity occurred at 50 microM thiopental, and appeared to result from direct activation of GABAA-gated chloride currents, observed with voltage clamp recordings, and mimicked with a direct acting GABAA agonist, muscimol (1 microM). Isoelectric activity occurred at 100 microM thiopental, and likely resulted from reduced glutamatergic transmission, evidenced by depressed excitatory postsynaptic potentials. Glutamatergic excitation was required for burst suppression activity, because glutamate receptor antagonists blocked thiopental-induced bursts; forcing a transition to isoelectric activity.

Conclusions

Thiopental produced a continuum of EEG-like states in brain slices similar to those observed in vivo. The progression of thiopental-induced effects appear to have resulted from specific cellular actions that were recruited in a concentration-dependent manner. Progressive enhancement of synaptic inhibition followed by depression of excitatory transmission led to micro-EEG frequency slowing, burst suppression, and isoelectric activity.
Nitric Oxide Mediates Hepatic Cytochrome P450 Dysfunction Induced by Endotoxin
Authors: Muller Claudia M. , Scierka Annette , Stiller Richard L. , Kim Yong-Myeong , Cook Ryan D. , Lancaster Jack R. , Buffington Charles W. , Watkins David W.
Published: November 2003

Background

Animals subjected to immunostimulatory conditions (sepsis) exhibit decreased total cytochrome P450 content and decreased P450-dependent drug metabolism. Cytochrome P450 function is of clinical significance because it mediates the metabolism of some opioid and hypnotic drugs. The authors tested the hypothesis that reduced P450 function and decreased drug metabolism in sepsis are mediated by endotoxin-enhanced synthesis of nitric oxide.

Methods

Hepatic microsomes were prepared from male Sprague-Dawley rats in nontreated rats, rats pretreated with phenobarbital and rats receiving aminoguanidine or NG-L-monomethyl-arginine alone. Nitric oxide synthesis was augmented for 12 h with a single injection of bacterial lipopolysaccharides. Nitric oxide synthase was inhibited with aminoguanidine or N(G)-L-monomethyl-arginine during the 12 h of endotoxemia in some animals. Plasma nitrite and nitrate concentrations were measured in vivo, and total microsomal P450 content, and metabolism of ethylmorphine and midazolam in vitro.

Results

Administration of endotoxin increased plasma nitrite and nitrate concentrations, decreased total cytochrome P450 content, and decreased metabolism of ethylmorphine and midazolam. Inhibition of nitric oxide formation by aminoguanidine or N(G)-L-monomethyl-arginine partially prevented the endotoxin-induced effects in the nontreated and phenobarbital-treated groups. Aminoguanidine or N(G)-L-monomethyl-arginine alone did not have an effect on either total cytochrome P450 content or P450-dependent drug metabolism. Plasma nitrite and nitrate concentrations correlated significantly negatively with P450 content (nontreated r = -0.88, phenobarbital r = -0.91), concentrations of formed formaldehyde (nontreated r = -0.87, phenobarbital r = -0.95), and concentrations of midazolam metabolites (4-OH midazolam nontreated r = -0.88, phenobarbital r = -0.93, and 1'-OH midazolam nontreated r = -0.88, phenobarbital r = -0.97).

Conclusions

Altered hepatic microsomal ethylmorphine and midazolam metabolism during sepsis is mediated in large part by nitric oxide.
Exacerbation or Unmasking of Focal Neurologic Deficits by Sedatives
Authors: Thal Gary D. , Szabo Michele D. , Lopez-Bresnahan Maria , Crosby Gregory
Published: November 2003

Background

Transient focal neurologic deficits have been observed in patients emerging from brain tumor or carotid surgery, and a pharmacologic effect of anesthetic agents has been proposed as the cause of such neurologic dysfunction. Therefore, the effect of sedation with midazolam or fentanyl on motor neurologic function was studied prospectively and preoperatively in patients with carotid disease or mass lesions of the brain.

Methods

Fifty-four unpremedicated adult patients with carotid disease or a brain tumor were given small intravenous doses of either 2.8 +/- 1.3 mg midazolam or 170 +/- 60 micrograms fentanyl in the preoperative period. A thorough motor examination was performed at baseline and after sedation by an individual who was unaware of the details of the patient's disease or symptoms. A mental status examination also was performed to control for the effects of inattentiveness or lack of cooperation during the neurologic examination.

Results

Patients were sedated mildly but were fully cooperative. Focal motor deterioration occurred after sedation in 30% of patients, and the incidence was similar in patients in the fentanyl and midazolam groups. Among patients with a focal motor abnormality on baseline examination or a resolved prior motor deficit, 73% had exacerbation or unmasking of these signs by sedation, whereas no patient without a prior history of motor dysfunction had a sedative-induced change. Sedative-induced changes in neurologic function ranged from unilateral mild weakness to complete plegia, but appeared to be transient in nature.

Conclusions

Sedation with midazolam or fentanyl can transiently exacerbate or unmask focal motor deficits in patients with prior motor dysfunction.
Influence of Volatile Anesthetics on Left Ventricular Afterload In Vivo
Authors: Lowe Dermot , Hettrick Douglas A. , Pagel Paul S. , Warltier David C.
Published: November 2003

Background

This investigation examined the effects of desflurane and sevoflurane on quantitative indices of left ventricular afterload derived from aortic input impedance (Zin) interpreted using a three-element Windkessel model.

Methods

After Animal Care Committee approval, dogs (n = 8) were chronically instrumented for measurement of systemic hemodynamics including aortic blood pressure and flow. On separate days, aortic pressure and flow waveforms were recorded under steady-state conditions in the conscious state and after equilibration for 30 min at 1.1, 1.3, 1.5, and 1.7 minimum alveolar concentration of desflurane or sevoflurane. Aortic input impedance spectra were obtained via power spectral analysis of aortic pressure and flow waveforms. Characteristic aortic impedance (Zc) and total arterial resistance were calculated as the mean of the magnitude of Zin between 2 and 15 Hz and the difference between Zin at zero frequency and Zc, respectively. Total arterial compliance (C) was calculated from aortic pressure and flow waveforms using the Windkessel model.

Results

Desflurane and sevoflurane increased heart rate and decreased systolic, diastolic, and mean arterial pressure, left ventricular systolic pressure, left ventricular peak positive rate of increase in left ventricular pressure, percent segment shortening, and stroke volume. Sevoflurane, but not desflurane, decreased cardiac output. Desflurane, but not sevoflurane, decreased systemic vascular resistance. Desflurane decreased R (3,170 +/- 188 during control to 2441 +/- 220 dynes.second.centimeter-5 at 1.7 minimum alveolar concentration) and did not alter C and Zc. In contrast, sevoflurane increased C (0.57 +/- 0.05 during control to 0.79 +/- 0.05 ml/ mmHg at 1.7 minimum alveolar concentration) and Zc (139 +/- 10 during control to 194 +/- 14 dynes.second.centimeter-5 at 1.7 minimum alveolar concentration) but did not change R.

Conclusions

The results indicate that desflurane and sevoflurane produce substantially different effects on left ventricular afterload in chronically instrumented dogs. Desflurane-induced decreases in systemic vascular resistance occur primarily because of effects on arteriolar resistance vessels. In contrast, sevoflurane increased C and Zc concomitant with pressure-dependent reductions in aortic diameter, suggesting that this anesthetic may alter left ventricular afterload by affecting the mechanical properties of the aorta.
Volatile Anesthetics Depress Spinal Motor Neurons
Authors: Rampil Ira J. , King Bryan S.
Published: November 2003

Background

Depression of spinal alpha-motor neurons apparently plays a role in the surgical immobility induced by isoflurane. Using the noninvasive technique of F-wave analysis, the authors tested the hypothesis that depressed motor neuron excitability is an effect common to other clinically relevant inhaled anesthetics.

Methods

The authors measured F-wave amplitude in rats anesthetized with desflurane, enflurane, halothane, or sevoflurane. Each animal received one anesthetic at five equipotent anesthetic concentrations (0.6, 0.8, 1.2, and 1.6 minimum alveolar concentration [MAC] and 0.8 MAC with 65% N2O). F waves were detected as late potentials in electromyographic responses evoked in the intrinsic muscles of the hind paw after monopolar stimulation of the ipsilateral posterior tibial nerve.

Results

All tested inhaled anesthetics depressed F-wave amplitude but not M-wave (orthodromic, early muscle activation) amplitude, and increased M-F latency in a dose-dependent manner. At 1.0 MAC, the estimated F/M ratio was 70 +/- 13% SD of that at baseline (0.6 MAC). Nitrous oxide added to 0.8 MAC of the potent vapors depressed F/M ratio by 63 +/- 17%.

Conclusions

All anesthetics tested appeared to depress the excitability of spinal motor neurons. This effect may contribute to surgical immobility, and its magnitude is comparable at equipotent concentrations of agents. The authors hypothesize that this effect is due to hyperpolarization, although, currently, there is insufficient information to discriminate between pre- and postsynaptic mechanisms.
Cardiac and Regional Hemodynamic Interactions between Halothane and Nitric Oxide Synthase Activity in Dogs
Authors: Chelly Jacques E. , Doursoot Marie-Francoise , Lechevalier Thierry , Liang Yang Yan , Chelly Frank , Hartley Craig , Kilbourn Robert G.
Published: November 2003

Background

In vitro, halothane appears to affect the role played by nitric oxide in the regulation of vascular tone and cardiac function. In vivo, the results of the interactions between halothane and the nitric oxide pathway remain controversial. The authors investigated the effects of halothane on the cardiac and regional hemodynamic properties of N-methyl-L-arginine (NMA), a specific nitric oxide synthase inhibitor, in dogs.

Methods

Twenty-five dogs were chronically instrumented. Aortic pressure, the first derivative of left ventricular pressure, cardiac output, heart rate, and carotid, coronary, mesenteric, hepatic, portal and renal blood flows were continuously recorded. N-methyl-L-arginine was infused intravenously at 20 mg/kg over 1 min in awake dogs (n = 11) and in 1.2% halothane-anesthetized dogs (n = 10). As a control group, the remaining four dogs were studied awake and during 1.2% halothane for 2 h in the absence of NMA.

Results

In awake dogs, NMA produced a sustained pressor response (34%) and systemic vasoconstriction (40%) associated with a decrease in cardiac output (16%). Regional circulation changes included an immediate and transient increase in carotid (43%) and coronary (237%) blood flows and a subsequent decrease in carotid blood flow (25%). Hepatic and mesenteric blood flows also decreased, by 43% and 16%, respectively. Except for the coronary circulation, regional vascular resistance increased significantly. Halothane did not affect the pressor response to NMA but did blunt the cardiac output changes. Consequently, the systemic vasoconstriction after nitric oxide synthase inhibition was of shorter duration and of lesser magnitude during halothane anesthesia. Halothane also blunted the carotid, mesenteric, and renal vasoconstriction induced by NMA. Finally, in 1.2% halothane-anesthetized dogs, NMA induced a coronary vasoconstriction.

Conclusions

Halothane minimally interferes with the systemic and regional hemodynamic consequences of nitric oxide synthase blockade. The nature and magnitude of the interaction depend on the territory in which they occur.
Concomitant Administration of Morphine and an N-Methyl-D-Aspartate Receptor Antagonist Profoundly Reduces Inflammatory Evoked Spinal c-Fos Expression
Authors: Honore Prisca D. , Chapman Victoria , Buritova Jaroslava , Besson Jean-Marie
Published: November 2003

Background

After intraplantar injection of carrageenin, peripheral inflammation and spinal c-Fos expression are extensive, with the latter being sensitive to both large doses of morphine or N-methyl-D-aspartate receptor antagonism. The authors investigated the effects of coadministered morphine and (+)-HA966, a functional antagonist at the glycine site of the N-methyl-D-aspartate receptor, on the two parameters.

Methods

The effects of morphine, (+)-HA966 and coadministration of morphine and (+)-HA966 on spinal c-Fos expression in segments L4-L5 of the spinal cord and peripheral edema, induced at 1.5 h and 3 h after intraplantar carrageenin (6 mg/150 microliters) were studied.

Results

Previous coadministration of 0.3 mg/kg systemic morphine and 2.5 mg/kg subcutaneous (+)-HA966 significantly reduced c-Fos expression induced 1.5 h, but not 3 h, after carrageenin administration. However, coadministration of a larger dose of morphine (3 mg/kg) with (+)-HA966 (2.5 mg/kg) reduced c-Fos expression at 3 h after carrageenin administration, in a partially naloxone-reversible manner.

Conclusions

Concurrent mu-opioid receptor activation and N-methyl-D-aspartate receptor antagonism reduces nociceptive transmission at the level of the spinal cord, as shown by the reduction of carrageenin-evoked c-Fos expression.
Intramuscular Rocuronium in Infants and Children
Authors: Reynolds Lynne M. , Lau Marie , Brown Ronald , Luks Andrew , Fisher Dennis M.
Published: November 2003

Background

Rocuronium's rapid onset and intermediate duration of action with intravenous administration suggests that intramuscular administration might facilitate tracheal intubation without producing prolonged paralysis. Accordingly, in infants and children, the authors measured onset at the adductor pollicis and respiratory muscles to determine the optimal dose (phase I), then gave this optimal dose to determine the optimal time for tracheal intubation (phase II).

Methods

The authors studied 45 unpremedicated patients aged 3 months to 5 yr. In phase I, 25 patients were anesthetized with nitrous oxide and halothane and breathed spontaneously; twitch tension and minute ventilation were measured. Rocuronium (800-2,400 micrograms/kg) was injected into the quadriceps or deltoid muscle; doses varied, using an "up-down" technique, the goal being to bracket the dose depressing twitch 75-90% within 5 min. In phase II, deltoid injections of the optimal dose from phase I (infants: 1,000 micrograms/kg; children: 1,800 micrograms/kg) were given to 20 patients anesthetized with 0.82-1.0% halothane. Tracheal intubation was attempted 1.5-3.0 min later; time to tracheal intubation was varied, using an "up-down" technique.

Results

In phase I, 5 of 7 patients given quadriceps injections (1,200-2,200 micrograms/kg) had slow onset of twitch and ventilatory depression. With deltoid injections (800-2,400 micrograms/kg), all patients developed complete twitch depression; median time to 50% depression of minute ventilation was 3.2 min in infants and 2.8 min in children. In phase II, intubating conditions were consistently adequate or good-excellent at 2.5 min in infants and 3.0 min in children. Initial twitch recovery was at 57 +/- 13 min (mean +/- SD) in infants and 70 +/- 23 min in children.

Conclusions

Deltoid injections of rocuronium, 1,000 micrograms/kg in infants and 1,800 micrograms/kg in children, rapidly permit tracheal intubation in infants and children, despite a light plane of anesthesia. Duration of action of these large doses might limit clinical utility.
Changing Anesthesiologists' Practice Patterns
Authors: Cohen Marsha M. , Rose Keith D. , Yee D. A.
Published: November 2003

Background

Because the ultimate purpose of new medical knowledge is to achieve improved health outcomes, physicians need to possess and use this knowledge in their practice. The authors introduced enhanced education and individualized feedback to reduce postoperative nausea and vomiting (PONV). The primary objective was to increase anesthesiologists' use of preventive measures to reduce PONV, and the secondary objective was to determine whether patient outcomes were improved.

Methods

After obtaining hospital ethics committee approval, the effect of education and feedback on anesthesiologist performance and the rate of PONV in major surgery elective inpatients during a 2-yr period was assessed. After baseline data collection (6 months), anesthesiologists at the study hospital received enhanced education (8 months) and individualized feedback (10 months). Parallel data collection was performed at a control hospital at which practice was continued as usual. The education promoted preventive measures (antiemetic premedication, nasogastric tubes, droperidol, metoclopramide). Individualized feedback provided the number of patients receiving promoted measures and the rate of PONV. The mean percentage of anesthesiologists' patients receiving at least one promoted measure and the rate of PONV were compared with baseline levels.

Results

At the study hospital, there was a significant increase in the mean percentage of the anesthesiologists' female patients receiving a preventive measure as well as a significant increase in the use of droperidol > or = 1 mg (P < 0.05) for all patients. The use of other promoted measures was unaffected. Absolute rates of PONV were unaffected at the study hospital until the post-feedback period (decrease of 8.8% between baseline and post-feedback (P = 0.015)).

Conclusion

It was demonstrated that enhanced education and individualized feedback can change anesthesiologists' practice patterns. The actual benefit to patients from use of preventive measures was limited when used in the everyday clinical situation. Therefore, only modest decreases in PONV were achieved, despite the use of preventive measures.
Perioperative Respiratory Complications in Patients with Asthma
Authors: Warner David O. , Warner Mark A. , Barnes Roxann D. , Offord Kenneth P. , Schroeder Darrell R. , Gray Darryl T. , Yunginger John W.
Published: November 2003

Background

Patients with asthma are thought to be at high risk for pulmonary complications to develop during the perioperative period, and these complications may lead to serious morbidity. Existing medical records were reviewed to determine the frequency of and risk factors for perioperative pulmonary complications in a cohort of residents of Rochester, Minnesota, who had asthma and who underwent anesthesia and surgery at the Mayo Clinic in Rochester.

Methods

Medical records were reviewed for all residents of Rochester, Minnesota, who were initially diagnosed as having definite asthma according to strict criteria from 1 January 1964 through 31 December 1983 who subsequently had at least one surgical procedure involving a general anesthetic or central neuroaxis block at the Mayo Clinic (n = 706).

Results

Bronchospasm was documented in the perioperative records of 12 patients (1.7% [exact 95% confidence interval, 0.9 to 3%]). Postoperative respiratory failure developed in one of these patients. Laryngospasm developed in two additional patients during operation. All episodes of bronchospasm and laryngospasm in the immediate perioperative period were treated successfully. No episodes of pneumothorax, pneumonia, or death in the hospital were noted. For univariate analysis, characteristics associated with complications included the recent use of antiasthmatic drugs, recent asthma symptoms, and recent therapy in a medical facility for asthma. Patients in whom complications developed were significantly older at diagnosis and at surgery.

Conclusions

The frequency of perioperative bronchospasm and laryngospasm was surprisingly low in this cohort of persons with asthma. These complications did not lead to severe respiratory outcomes in most patients. The frequency of complications was increased in older patients and in those with active asthma.
Do Children Who Experience Laryngospasm Have an Increased Risk of Upper Respiratory Tract Infection?
Authors: Schreiner Mark S. , O'Hara Irene , Markakis Dorothea A. , Politis George D.
Published: November 2003

Background

Laryngospasm is the most frequently reported respiratory complication associated with upper respiratory infection and general anesthesia in retrospective studies, but prospective studies have failed to demonstrate any increase in risk.

Methods

A case-control study was performed to examine whether children with laryngospasm were more likely to have an upper respiratory infection on the day of surgery. The parents of all patients (N = 15,183) who were admitted through the day surgery unit were asked if their child had an active or recent (within 2 weeks of surgery) upper respiratory infection and were questioned about specific signs and symptoms to determine if the child met Tait and Knight's definition of an upper respiratory infection. Control subjects were randomly selected from patients whose surgery had occurred within 1 day of the laryngospasm event.

Results

Patients who developed laryngospasm (N = 123) were 2.05 times (95% confidence interval 1.21-3.45) more likely to have an active upper respiratory infection as defined by their parents than the 492 patients in the control group (P < or = 0.01). The development of laryngospasm was not related to Tait and Knight's definition for an upper respiratory infection or to recent upper respiratory infection. Children with laryngospasm were more likely to be younger (odds ratio = 0.92, 95% confidence interval 0.87-0.99), to be scheduled for airway surgery (odds ratio = 2.08, 95% confidence interval 1.21-3.59), and to have their anesthesia supervised by a less experienced anesthesiologist (odds ratio = 1.69, 95% confidence interval 1.04-2.7) than children in the control group.

Conclusion

Laryngospasm was more likely to occur in children with an active upper respiratory infection, children who were younger, children who were undergoing airway surgery, and children whose anesthesia were supervised by less experienced anesthesiologists. Understanding the risk factors and the magnitude of the likely risk should help clinicians make the decision as to whether to anesthetize children with upper respiratory infection.
Single Injection Thermodilution
Authors: Jansen Jos R. C. , Schreuder Jan J. , Settels Jos J. , Kornet Lilian , Penn Olaf C. K. M. , Mulder Paul G. H. , Versprille Adrian , Wesseling Karel H.
Published: November 2003

Background

Application of the Stewart-Hamilton equation in the thermodilution technique requires flow to be constant. In patients in whom ventilation of the lungs is controlled, flow modulations may occur leading to large errors in the estimation of mean cardiac output.

Methods

To eliminate these errors, a modified equation was developed. The resulting flow-corrected equation needs an additional measure of the relative changes of blood flow during the period of the dilution curve. Relative flow was computed from the pulmonary artery pressure with use of the pulse contour method. Measurements were obtained in 16 patients undergoing elective coronary artery bypass surgery. In 11 patients (group A), pulmonary artery pressure was measured with a catheter tip transducer, in a partially overlapping group of 11 patients (group B), it was measured with a fluid-filled system. For reference cardiac output we used the proven method of four uncorrected thermodilution estimates equally spread over the ventilatory cycle.

Results

A total of 208 cardiac output estimates was obtained in group A, and 228 in group B. In group B, 48 estimates could not be corrected because of insufficient pulmonary artery pressure waveform quality from the fluid-filled system. Individual uncorrected Stewart-Hamilton estimates showed a large variability with respect to their mean. In group A, mean cardiac output was 5.01 l/min with a standard deviation of 0.53 l/min, or 10.6%. After flow correction, this scatter decreased to 5.0% (P < 0.0001). With no bias, the corresponding limits of agreement decreased from +/- 1.06 to +/- 0.5 l/min after flow correction. In group B, the scatter decreased similarly and the limits of agreement also became +/- 0.5 l/min after flow correction.

Conclusion

It was concluded that a single thermodilution cardiac output estimate using the flow-corrected equation is clinically feasible. This is obtained at the cost of a more complex computation and an extra pressure measurement, which often is already available. With this technique it is possible to reduce the fluid load to the patient considerably.