bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of hazardous—harmful drinking in a southern Thai community
Authors: ASSANANGKORNCHAIMD SAWITRI , PINKAEW PATTAREE , APAKUPAKUL NUALTA
Published: November 2003

The objective of this study was to identify the prevalence and characteristics of hazardous –harmful drinkers in a Thai community population using a cross‐sectional survey in two urban and five rural areas in Southern Thailand. Face‐to‐face interviews were conducted with 1005 subjects, aged ≥ 35, at the community centres to collect data on demographic characteristics and smoking and drinking patterns. The Alcohol Use Identification Test (AUDIT) was used to classify the subjects into three groups: hazardous—harmful drinkers (AUDIT ≥ 8), non‐problem drinkers (AUDIT=1–7) and non‐drinkers (AUDIT=0). Blood samples were drawn from 200 randomly selected subjects to determine the gamma glutamyltransferease (GGT) level. The analysis was performed on 898 respondents, 325 males and 573 females. Age‐adjusted prevalence of hazardous — harmful drinkers was 10% (27% in males and 1% in females). Adjusted for other variables, men were seven times (95% CI = 4.2–11.5) more likely to be non‐problem drinkers and 42 times (95% CI = 18.1–99.0) more likely to be hazardous — harmful drinkers than women. Median intensity of drinking was 43 g and 25 g per drinking day in the hazardous — harmful and non‐problem drinkers, respectively. Of all the subjects, 48%, 25% and 15% of the hazardous — harmful, non‐problem and non‐drinkers had abnormal GGT. Hazardous — harmful drinking is a prevalent problem in male general population in Thailand.
A review of psychosocial interventions for amphetamine use
Authors: BAKER AMANDA , LEE NICOLE K.
Published: November 2003

There are clear signs that amphetamine use is increasing in Australia and internationally, yet there are few services that offer amphetamine‐specific interventions. This review examines the evidence for the use of psychosocial interventions for amphetamine users. The literature is very limited in the number of well‐conducted, controlled studies, but the evidence available suggests that cognitive‐behavioural therapy appears to be current best practice. Motivational interviewing has been recommended as a strategy to assist those ambivalent for treatment. There is also some evidence that contingency management is effective while clients are in treatment. The effectiveness of other types of intervention is not well supported. The literature is particularly hindered by a paucity of well‐conducted studies among primary amphetamine users. Recommendations about appropriate interventions for use in clinical settings are offered and directions for future research are considered.
Oral Tolerance and Pyruvate Dehydrogenase in Patients with Primary Biliary Cirrhosis
Authors: Suzuki Ayako , van de Water Judy , Gershwin M. Eric , Jorgensen Roberta , Angulo Paul , Lindor Keith
Published: November 2003

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the immunological destruction of intralobular bile ducts and serum anti‐mitochondrial antibodies (AMA). Based upon previous work of oral tolerance and autoimmunity, we hypothesized that feeding the mitochondrial autoantigens of PBC would alter the clinical course and the level of antimitochondrial antibodies. The bovine pyruvate dehydrogenase complex (PDC) was purified and 5 mg fed in gelatin capsules to 6 patients with early stage PBC for 6 months. Antimitochondrial antibodies and liver biochemistries were measured at every 3 months for 12 months. The clinical trial was completed for all patients except for 1 who showed deterioration of pre‐existing skin rash during treatment, which disappeared within 2 weeks after treatment was discontinued. However, after 1 year, neither the titers of AMAs nor liver biochemistries were significantly changed by this treatment. This is the first trial to test the efficacy of oral tolerance induction in PBC. However, the data, which limited in scope, did not demonstrate efficacy and further highlights the difficulties in showing continuing evidence of tolerance induction in autoimmunity.
Halothane, Isoflurane, Xenon, and Nitrous Oxide Inhibit Calcium ATPase Pump Activity in Rat Brain Synaptic Plasma Membranes
Authors: Franks John J. , Horn Jean-Louis , Janicki Piotr K. , Singh Gurkeerat
Published: November 2003

Background

Perturbation of neuronal calcium homeostasis may alter neurotransmission in the brain, a phenomenon postulated to characterize the anesthetic state. Because of the central role of plasma membrane Ca(2+)-ATPase (PMCA) in maintaining Ca2+ homeostasis, the authors examined the effect of several inhalational anesthetics on PMCA function in synaptic plasma membranes (SPM) prepared from rat brain.

Methods

Ca(2+)-ATPase pumping activity was assessed by measurement of ATP-dependent uptake of Ca2+ by SPM vesicles. ATPase hydrolytic activity was assessed by spectrophotometric measurement of inorganic phosphate (Pi) released from ATP. For studies of anesthetic effects on PMCA activity, Ca2+ uptake or Pi release was measured in SPM exposed to halothane, isoflurane, xenon, and nitrous oxide at partial pressures ranging from 0 to 1.6 MAC equivalents. Halothane and isoflurane exposures were carried out under a gassing hood. For xenon and nitrous oxide exposures, samples were incubated in a pressure chamber at total pressures sufficient to provide anesthetizing partial pressures for each agent.

Results

Dose-related inhibition of Ca(2+)-ATPase pumping activity was observed in SPM exposed to increasing concentrations of halothane and isoflurane, confirmed by ANOVA and multiple comparison testing (P < 0.05). Concentrations of halothane and isoflurane equivalent to one minimum effective dose (MED) depressed PMCA pumping approximately 30%. Xenon and nitrous oxide also inhibited Ca2+ uptake by SPM vesicles. At partial pressures of these two gases equivalent to 1.3 MAC, PMCA was inhibited approximately 20%. Hydrolysis of ATP by SPM fractions was also inhibited in a dose-related fashion. An additive effect occurred when 1 vol% of halothane was added to xenon or nitrous oxide at partial pressures equivalent to 0-1.6 MAC for the latter two agents.

Conclusions

Plasma membranes Ca(2+)-ATPase is significantly inhibited, in a dose-related manner, by clinically relevant partial pressures of halothane, isoflurane, xenon, and nitrous oxide. Furthermore, these anesthetics inhibit PMCA activity in accordance with their known potencies, and an additive effect was observed. How inhalational anesthetics inhibit the PMCA pump is not known at this time. It is noteworthy that the only shared characteristic of this group of agents of widely different structure is anesthetic action. The relevance of this dual commonality, anesthetic action and PMCA inhibition, to actual production of the anesthetic state remains to be determined.
Stable Inhibition of Brain Synaptic Plasma Membrane Calcium ATPase in Rats Anesthetized with Halothane
Authors: Franks John J. , Horn Jean-Louis , Janicki Piotr K. , Singh Gurkeerat
Published: November 2003

Background

The authors recently showed that plasma membrane Ca(2+)-ATPase (PMCA) activity in cerebral synaptic plasma membrane (SPM) is diminished in a dose-related fashion during exposure in vitro to halothane, isoflurane, xenon, and nitrous oxide at clinically relevant partial pressures. They have now extended their work to in vivo studies, examining PMCA pumping in SPM obtained from control rats decapitated without anesthetic exposure, from rats decapitated during halothane anesthesia, and from rats decapitated after recovery from halothane anesthesia.

Methods

Three treatment groups were studied: 1) C, control rats that were decapitated without anesthetic exposure, 2) A, anesthetized rats exposed to 1 minimum effective dose (MED) for 20 min and then decapitated, and 3) R, rats exposed to 1 MED for 20 min and then decapitated after recovery from anesthesia, defined as beginning to groom. Plasma membrane Ca(2+)-ATPase pumping and Ca(2+)-dependent ATPase hydrolytic activity, as well as sodium-calcium exchanger activity and Na+-K+-ATPase hydrolytic activity, were assessed in cerebral SPM. In addition, halothane effect on smooth endoplasmic reticulum Ca(2+)-ATPase (SERCA) was examined.

Results

Plasma membrane Ca(2+)-ATPase transport of Ca2+ into SPM vesicles from anesthetized rats was reduced to 71% of control (P < 0.01) compared with 113% of control for the recovered group (NS). No depression by halothane of SERCA activity, sodium-calcium exchanger, or Na+-K+-ATPase activity was noted among the CAR treatment groups.

Conclusions

Plasma membrane Ca(2+)-ATPase is selectively and stably inhibited in cerebral SPM from rats killed while anesthetized with halothane, compared with rats killed without anesthesia or after recovery from anesthesia. The studies described in this report, in conjunction with previously reported inhibition of PMCA activity in vitro by a wide range of anesthetic agents, indicate a relationship between inhibition of PMCA and action of inhalational anesthetics.
Platelet Factor 4 Injection Produces Acute Pulmonary Hypertension in the Awake Lamb
Authors: Kurrek Matt M. , Winkler Marianne , Robinson Dwight R. , Zapol Warren M.
Published: November 2003

Background

Reversal of heparin anticoagulation by intravenous protamine sulfate consistently produces acute pulmonary vasoconstriction mediated by the release of thromboxane in the awake lamb. Recently, recombinant platelet factor 4 (rPF4) has been cloned, expressed in Escherichia coli, and infused to reverse heparin anticoagulation in the rat, without producing adverse hemodynamic or pulmonary morphologic effects. The authors sought to learn whether intravenous administration of PF4 is devoid of side effects in the pulmonary circulation of lambs.

Methods

The authors evaluated the hemodynamic response and plasma release rates of thromboxane during intravenous challenges with heparin-rPF4 (n = 2), rPF-free carrier (n = 5), rPF4 (n = 5), rPF4 after indomethacin (n = 5), protamine (n = 5) and heparin-protamine (n = 5) in 17 awake, hemodynamically monitored lambs. Each lamb underwent up to three random challenges with a 2-h recovery period between each challenge.

Results

In two lambs, systemic anticoagulation with heparin followed by reversal of anticoagulation with an intravenous bolus of rPF4 (4 mg/kg) led to acute pulmonary vasoconstriction and hypertension with the release of thromboxane (peak pulmonary artery pressure [Ppa] 40 and 33 mmHg and peak plasma thromboxane B2 50 and 30 ng/ml, respectively). Intravenous administration of rPF4 (1.5 mg/kg) alone increased the Ppa from 17.2 +/- 0.7 mmHg (mean +/- SEM) at baseline to 31.2 +/- 2 mmHg at 1 min (n = 5, P < 0.05). This was associated with an increase of plasma thromboxane B2 from 0.06 +/- 0.02 to 3.96 +/- 1.21 ng/ml. Acute pulmonary vasoconstriction lasted approximately 5 min and was completely prevented by pre-treatment with oral indomethacin (10 mg/kg). Intravenous bolus administration of rPF4 carrier (n = 5) or protamine (2 mg/kg) alone (n = 5) did not induce pulmonary hypertension or the release of thromboxane. In five lambs, intravenous heparin (200 U/kg) followed by protamine (2 mg/kg) consistently produced acute pulmonary vasoconstriction and hypertension.

Conclusions

Intravenous injection of human rPF4 into the awake lamb produces acute pulmonary vasoconstriction and hypertension associated with thromboxane release into circulating blood. The effects of rPF4 on the pulmonary vasculature should be evaluated in primates before rPF4 is substituted for protamine in reversing heparin anticoagulation in humans.
The Addition of 7.5% Glucose Does Not Alter the Neurotoxicity of 5% Lidocaine Administered Intrathecally in the Rat
Authors: Sakura Shinichi , Chan Vincent W. S. , Ciriales Ricardo , Drasner Kenneth
Published: November 2003

Background

Recent reports of major and minor neurologic sequelae after spinal anesthesia have generated concern regarding the safety of some currently used intrathecal agents. The role of glucose, if any, in neurotoxic injury associated with spinal anesthesia is not known. The current experiments sought to determine whether the presence of 7.5% glucose alters the neurotoxicity of intrathecally administered 5% lidocaine.

Methods

Two experiments were performed. First, 48 rats were implanted with an intrathecal catheter and randomly divided into eight equal groups. Each animal received a single intrathecal infusion of 5% lidocaine (groups P1-P4) or 5% lidocaine with 7.5% glucose (G1-G4) for 0.5, 1, 2, or 4 h at a rate of 1 microliter/min. Sensory function was assessed using the tail-flick test; a deficit was defined as a complete lack of response to the heat stimulus at the proximal, mid or distal portion of the tail persisting 4 days after the infusion. In the second experiment, 60 rats were randomly divided into two groups to receive a 1-h intrathecal infusion of 5% lidocaine or 5% lidocaine with 7.5% glucose. Animals were evaluated for increase in the latency of the tail-flick reflex 4 days after infusion.

Results

In the first experiment, the two lidocaine solutions produced similar dose-dependent loss of sensory function. In the second experiment, the two solutions induced similar alterations in tail-flick latency.

Conclusions

The presence of 7.5% glucose does not affect the potential of intrathecally administered 5% lidocaine to induce sensory impairment. These findings provide further support for the hypothesis that recent injuries after spinal anesthesia resulted from a direct neurotoxic effect of the local anesthetic.
Pulsatile Versus Nonpulsatile Flow
Authors: Hindman Bradley J. , Dexter Franklin , Smith Tom , Cutkomp Johann
Published: November 2003

Background

Although pulsatile and nonpulsatile cardiopulmonary bypass (CPB) do not differentially affect cerebral blood flow (CBF) or metabolism during hypothermia, studies suggest pulsatile CPB may result in greater CBF than nonpulsatile CPB under normothermic conditions. Consequently, nonpulsatile flow may contribute to poorer neurologic outcome observed in some studies of normothermic CPB. This study compared CBF and cerebral metabolic rate for oxygen (CMRO2) between pulsatile and nonpulsatile CPB at 37 degrees C.

Methods

In experiment A, 16 anesthetized New Zealand white rabbits were randomized to one of two pulsatile CPB groups based on pump systolic ejection period (100 and 140 ms, respectively). Each animal was perfused at 37 degrees C for 30 min at each of two pulse rates (150 and 250 pulse/min, respectively). This scheme created four different arterial pressure waveforms. At the end of each perfusion period, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (microspheres), and CMRO2 (Fick) were measured. In experiment B, 22 rabbits were randomized to pulsatile (100-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 37 degrees C. At 30 and 60 min of CPB, physiologic measurements were made as before.

Results

In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all four waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile CPB (72 +/- 6 vs. 77 +/- 9 ml.100 g-1.min-1, respectively (median +/- quartile deviation)). CMRO2 did not differ between pulsatile and nonpulsatile CPB (4.7 +/- 0.5 vs. 4.1 +/- 0.6 ml O2.100 g-1.min-1, respectively) and decreased slightly (0.4 +/- 0.4 ml O2.100 g-1.min-1) between measurements.

Conclusions

During CPB in rabbits at 37 degrees C, neither CBF nor CMRO2 is affected by arterial pulsation. The absence of pulsation per se is not responsible for the small decreases in CMRO2 observed during CPB.
Recovery of Hepatic Drug Extraction after Hypothermic Preservation
Authors: Kelley Scott D. , Cauldwell Charles B. , Fisher Dennis M. , Lau Marie , Sharma Manohar L. , Weisiger Richard A.
Published: November 2003

Background

To determine whether liver preservation before transplantation impairs hepatic drug metabolism, hepatic extraction of drugs with different metabolic pathways (fentanyl, morphine, and vecuronium) in isolated rat livers was measured either immediately or after 24 h of hypothermia at 4 degrees C using a standard preservation-reperfusion sequence.

Methods

Isolated rat livers were perfused via the portal vein for 30 min to document initial viability. Test livers (n = 5) were perfused with iced Belzer solution, stored for 24 h at 4 degrees C, and flushed with 6% hetastarch. After hypothermic preservation for 24 h, or in control livers (n = 5) immediately after the 30-min perfusion, livers were perfused single-pass at a constant flow rate with solutions containing fentanyl, morphine, and vecuronium at 37 degrees C. Perfusate and bile samples were obtained at regular intervals for 64 min, after which liver tissue was harvested for analysis. Drug concentrations were measured using radioimmunoassay and gas chromatography. Metabolic capacity of the liver was estimated from the extraction fraction of each drug at steady-state.

Results

After warming to 37 degrees C, preserved livers consumed oxygen and produced bile at rates similar to that of control livers. Hypothermic preservation did not affect extraction of fentanyl and morphine. Vecuronium extraction was initially less in preserved livers, but this difference disappeared as the preserved livers returned to 37 degrees C (< 16 min). Biliary excretion and tissue concentrations of vecuronium were similar in each group.

Conclusions

Hypothermic preservation does not significantly impair extraction of these drugs in this liver preservation model. If these results apply to human liver transplantation, little danger of drug accumulation exists during the early postoperative period if hepatic function is normal.
Inhibition of Nociception-induced Spinal Sensitization by Anesthetic Agents
Authors: O'Connor Therese C. , Abram Stephen E.
Published: November 2003

Background

Subcutaneous injection of dilute formalin in the hind paw of the rat produces a biphasic nociceptive response. Initial C-fiber activity is accompanied by flinching of the paw for about 5 min (phase 1), followed by cessation of activity and resumption of flinching beginning 15 min after injection and lasting about 40 min or more (phase 2). The second phase depends on changes in dorsal horn cell function that occur shortly after the initial C-fiber discharge. It was previously shown that isoflurane, administered during phase 1, reduced phase 2 activity, but a combination of isoflurane and nitrous oxide given throughout phase 1 did not suppress spinal sensitization. The same model was used to determine the effects of several inhalation and intravenous anesthetic agents on phase 2 of the formalin test.

Methods

The formalin test was carried out on male Sprague-Dawley rats. Animals anesthetized briefly with halothane to facilitate formalin injection, were compared to animals that received 1 MAC anesthesia from 5 min before to 6 min after formalin injection using halothane, enflurane, isoflurane, desflurane, or 70% N2O, or a combination of nitrous oxide plus 1 MAC halothane. Animals that were given intravenous saline immediately before injection of formalin were compared to animals given either 20 mg/kg intravenous thiopental just before formalin injection or 10 mg/kg intravenous propofol just before and 3 mg/kg immediately after formalin injection. Flinches/minute were counted at 1 and 5 min after formalin injection and thereafter at 5-min intervals for 1 h. The total of 1- and 5-min flinches were considered phase 1 activity and the total of 10-60-min flinches were considered phase 2. Total phase 2 activity was compared between groups using one-way analysis of variance.

Results

Animals that received halothane, enflurane, isoflurane, desflurane, or nitrous oxide during phase 1 demonstrated a significant decrease in phase 2 activity when compared to controls, while those that received a combination of nitrous oxide and halothane exhibited no difference. Animals that received intravenous thiopental anesthesia during phase 1 demonstrated no difference in phase 2 activity when compared to controls, whereas those that received propofol during phase 1 demonstrated a significant decrease of phase 2 activity.

Conclusions

Volatile anesthetics or nitrous oxide significantly suppress spinal sensitization, whereas the combination of nitrous oxide plus halothane causes no suppression. Thiopental does not affect spinal sensitization, whereas propofol causes significant suppression. These results may have important implications regarding the development of postoperative pain.
Do Standard Monitoring Sites Reflect True Brain Temperature When Profound Hypothermia Is Rapidly Induced and Reversed?
Authors: Stone Gilbert J. , Young William L. , Smith Craig R. , Solomon Robert A. , Wald Alvin , Ostapkovich Noeleen , Shrebnick Debra B.
Published: November 2003

Background

Brain temperature is closely approximated by most body temperature measurements under normal anesthetic conditions. However, when thermal autoregulation is overridden, large temperature gradients may prevail. This study sought to determine which of the standard temperature monitoring sites best approximates brain temperature when deep hypothermia is rapidly induced and reversed during cardiopulmonary bypass.

Methods

Twenty-seven patients underwent cardiopulmonary bypass and deep hypothermic circulatory arrest in order for each to have a giant cerebral aneurysm surgically clipped. Brain temperatures were measured directly with a thermocouple embedded in the cerebral cortex. Eight other body temperatures were monitored simultaneously with less invasive sensors at standard sites.

Results

Brain temperature decreased from 32.6 +/- 1.4 degrees C (mean +/- SD) to 16.7 +/- 1.7 degrees C in 28 +/- 7 min, for an average cerebral cooling rate of 0.59 +/- 0.15 degrees C/min. Circulatory arrest lasted 24 +/- 15 min and was followed by 63 +/- 17 min of rewarming at 0.31 +/- 0.09 degrees C/min. None of the monitored sites tracked cerebral temperature well throughout the entire hypothermic period. During rapid temperature change, nasopharyngeal, esophageal, and pulmonary artery temperatures corresponded to brain temperature with smaller mean differences than did those of the tympanic membrane, bladder, rectum, axilla, and sole of the foot. At circulatory arrest, nasopharyngeal, esophageal, and pulmonary artery mean temperatures were within 1 degree C of brain temperature, even though individual patients frequently exhibited disparate values at those sites.

Conclusions

When profound hypothermia is rapidly induced and reversed, temperature measurements made at standard monitoring sites may not reflect cerebral temperature. Measurements from the nasopharynx, esophagus, and pulmonary artery tend to match brain temperature best but only with an array of data can one feel comfortable disregarding discordant readings.
Studies on the Safety of Chronically Administered Intrathecal Neostigmine Methylsulfate in Rats and Dogs
Authors: Yaksh Tony L. , Grafe Marjorie R. , Malkmus Shelle , Rathbun Michael L. , Eisenach James C.
Published: November 2003

Background

The spinal delivery of the cholinesterase inhibitor neostigmine yields analgesia in rats and augments the analgesic effects of alpha 2 agonists in sheep. To assess its activity in humans, preclinical toxicology studies to define its safety were required in two species.

Methods

Rats with chronic intrathecal catheters received daily injections of saline (vehicle) or 5 micrograms/10 microliters or 10 micrograms/10 microliters neostigmine HCl (n = 6/group) for 4 days and were observed for general behavior and nociception (52.5 degrees C hot plate). On day 6, rats were anesthetized and submitted to whole body perfusion/fixation. For dog studies, male beagles were prepared following rigid aseptic precautions with catheters passed from the cisterna magna to the lumbar intrathecal space. Catheters were connected to an external vest-mounted pump. Based on preliminary studies, ten implanted dogs were randomly assigned to receive infusions of neostigmine for 28 days (4 mg/4 ml/day; n = 6) or saline (4 ml/day; n = 4). At 28 days, dogs were anesthetized, cisternal cerebrospinal fluid was obtained, and dogs were submitted to perfusion-fixation. Rat and dog spinal cords were embedded, sectioned, stained, and assessed by the pathologist without knowledge of treatment.

Results

In rats, neostigmine produced a dose-dependent increase in hot plate latency, and no tolerance was observed. Mild tremor was observed but was not debilitating. Histopathology revealed a mild fibrotic reaction to the catheter with mixed signs of moderate, acute, and chronic inflammation with no differences between saline or drug groups. In dogs, neostigmine had no effect on blood pressure or on the skin twitch response but produced bradycardia and an increase in muscle tone. At sacrifice, cerebrospinal fluid protein, specific gravity, and glucose were elevated in both saline and neostigmine groups. Histopathology displayed a local reaction to the spinal catheter and a mixed acute and chronic inflammatory reaction. No group differences were observed. These results suggest that, at the neostigmine concentration of 1 mg/ml in the rat and dog and in doses up to 4 mg/day in the dog, there is no evidence of spinal tissue toxicity that can be attributed to the drug. This result, observed in two species, suggests that intrathecal neostigmine given in this manner is without distinguishable toxicity in these two models.
Mechanism of the Negative Inotropic Effect of Thiopental in Isolated Ferret Ventricular Myocardium
Authors: Housmans Philippe R. , Kudsioglu Turkan S. , Bingham Jonathan
Published: November 2003

Background

Thiopental's myocardial depressant effects are well known and most likely involve some alteration in intracellular Ca2+ homeostasis. The aim of this study was to investigate the mechanisms of thiopental's negative inotropic effects and its underlying mechanism in isolated ferret ventricular myocardium (which shows physiologic characteristics similar to human ventricular myocardium), and in frog ventricular myocardium, in which Ca2+ ions for myofibrillar activation are derived almost entirely from transsarcolemmal influx.

Methods

The authors analyzed the effects of thiopental after beta-adrenoceptor blockade on variables of contractility and relaxation, and on the free intracellular Ca2+ transient detected with the Ca(2+)-regulated photoprotein aequorin. Thiopental's effects also were evaluated in ferret right ventricular papillary muscles in which the sarcoplasmic reticulum (SR) function was impaired by ryanodine and in frog ventricular strips with little or no SR function.

Results

At concentration > or = 10(-4) M, which is in the high range of the clinically encountered free plasma thiopental concentrations, thiopental decreased contractility and the amplitude of the intracellular Ca2+ transient. At equal peak force, peak aequorin luminescence in 10(-4) M thiopental and [Ca2+]0 > 2.25 mM was slightly smaller than that in control conditions at [Ca2+]o = 2.25 mM. This indicates that thiopental causes a small increase in myofibrillar Ca2+ sensitivity. After inactivation of sarcoplasmic reticulum Ca2+ release with 10(-6) M ryanodine, a condition in which myofibrillar activation depends almost exclusively on transsarcolemmal Ca2+ influx, thiopental caused a further decrease in contractility and in the amplitude of the intracellular Ca2+ transient, and thiopental's relative negative inotropic effect was not different from that in control muscles not exposed to ryanodine. Thiopental, > or = 10(-4) M, decreased contractility in frog ventricular myocardium.

Conclusions

These findings indicate that the direct negative inotropic effect of thiopental results from a decrease in intracellular Ca2+ availability. At least part of thiopental's action is caused by inhibition of transsarcolemmal Ca2+ influx. These effects become apparent at concentrations routinely present during intravenous induction with thiopental.
Halothane Selectively Inhibits Nonshivering Thermogenesis
Authors: Dicker Andrea , Ohlson Kerstin B. E. , Johnson Lennart , Cannon Barbara , Lindahl Sten G.E. , Nedergaard Jan
Published: November 2003

Background

During halothane anesthesia, infants fail to increase oxygen consumption in response to a cold stimulus in the form of an increase in temperature gradient between body and environment. Based on recent observations with isolated brown-fat cells, it seemed feasible that this inability to respond could be due to an inhibition of nonshivering thermogenesis during halothane anesthesia.

Methods

The rate of oxygen consumption was measured in cold-acclimated hamsters and rats. The rate evoked by norepinephrine injection in hamsters at an environmental temperature of approximately 24 degrees C was used as a measure of the capacity for nonshivering thermogenesis. Anesthesia was induced by 3% halothane and maintained by 1.5% halothane. One experimental series with spontaneously breathing hamsters and a second control series with spontaneously breathing rats and with rats whose lungs were mechanically ventilated were conducted.

Results

Norepinephrine injection led to a fourfold increase in the rate of oxygen consumption in control hamsters; after this response had subsided, a second injection led to a similar effect. Halothane anesthesia caused an approximately 20% decrease in resting metabolic rate (P < 0.05) and a 70% inhibition of the thermogenic response to norepinephrine (P < 0.001). The halothane concentration yielding half-maximal inhibitory effect was estimated to be less than 1.0%. After the animals had recovered from halothane anesthesia, a completely restored thermogenic response to norepinephrine was observed. The inhibitory effect of halothane also was observed in hamsters maintained at normothermia and was therefore not secondary to the slight hypothermia that otherwise developed during anesthesia. In a series of control experiments, it was confirmed that rats also showed large thermogenic responses to norepinephrine injections, and it was found that, in spontaneously breathing halothane-anesthetized rats, the thermogenic response to norepinephrine was also much inhibited. Further, in halothane-anesthetized rats whose lungs were mechanically ventilated, and where blood gases were kept at virtually normal levels, the thermogenic response to norepinephrine was found to be similarly markedly inhibited.

Conclusions

A much diminished or abolished thermogenic response to injected norepinephrine was demonstrated in halothane-anesthetized animals. This implies that there would be a diminished ability to elicit nonshivering thermogenesis even when this process is physiologically induced. Such a diminished ability could in part explain the susceptibility of neonates and infants to hypothermia during halothane anesthesia.
Low-frequency Spectral Power of Heart Rate Variability Is Not a Specific Marker of Cardiac Sympathetic Modulation
Authors: Hopf Hans-Bernd , Skyschally Andreas , Heusch Gerd , Peters Jurgen
Published: November 2003

Background

Heart rate variability in the frequency domain has been proposed to reflect cardiac autonomic control. Therefore, measurement of heart rate variability may be useful to assess the effect of epidural anesthesia on cardiac autonomic tone. Accordingly, the effects of preganglionic cardiac sympathetic blockade by segmental epidural anesthesia were evaluated in humans on spectral power of heart rate variability. Specifically, the hypothesis that cardiac sympathetic blockade attenuates low-frequency spectral power, assumed to reflect cardiac sympathetic modulation, was tested.

Methods

Ten subjects were studied while supine and during a 15-min 40 degrees head-up tilt both before and after cardiac sympathetic blockade by segmental thoracic epidural anesthesia (sensory block: C6-T6). ECG, arterial pressure, and respiratory excursion (Whitney gauge) were recorded, and a fast-Fourier-transformation was applied to 512-s data segments of heart rate derived from the digitized ECG at the end of each intervention.

Results

With cardiac sympathetic blockade alone and the subjects supine, both low-frequency (LF, 0.06-0.15 Hz) and high-frequency (HF, 0.15-0.80 Hz) spectral power remained unchanged. During tilt, epidural anesthesia attenuated the evoked increase in heart rate (+11.min-1 +/- 7 SD vs. +6 +/- 7, P = 0.024). However, while during tilt cardiac sympathetic blockade significantly decreased the LF/HF ratio (3.68 +/- 2.52 vs. 2.83 +/- 2.15, P = 0.041 vs. tilt before sympathetic blockade), a presumed marker of sympathovagal interaction, absolute and fractional LF and HF power did not change.

Conclusions

Although preganglionic cardiac sympathetic blockade reduced the LF/HF ratio during tilt, it did not alter spectral power in the LF band during rest or tilt. Accordingly, low-frequency spectral power is unlikely to specifically reflect cardiac sympathetic modulation in humans.
Intraperitoneal Versus Interpleural Morphine or Bupivacaine for Pain after Laparoscopic Cholecystectomy
Authors: Schulte-Steinberg Hans , Weninger Ernst , Jokisch Dominik , Hofstetter Bernhard , Misera Axel , Lange Volker , Stein Christoph
Published: November 2003

Background

Opioids can produce peripheral analgesic effects by activation of opioid receptors on sensory nerves. This study was designed (1) to examine a novel route of opioid administration, the intraperitoneal injection; (2) to compare this to interpleural application, and (3) to compare opioid with local anesthetic effects under both conditions.

Methods

At the end of laparoscopic cholecystectomy, 110 patients received the following injections in a double-blind, randomized manner: Group 1 (n = 18) was given intraperitoneal morphine (1 mg in 20 ml saline) and 20 ml intravenous saline. Group 2 (n = 17) received intraperitoneal saline and 1 mg intravenous morphine. Group 3 (n = 15) received 20 ml 0.25% intraperitoneal bupivacaine and intravenous saline. Group 4 (n = 20) received interpleural morphine (1.5 mg in 30 ml saline) and 30 ml intravenous saline. Group 5 (n = 20) received interpleural saline and 1.5 mg intravenous morphine. Group 6 (n = 20) received 30 ml 0.25% interpleural bupivacaine and intravenous saline. Postoperative pain was assessed using a visual analog scale, a numeric rating scale, and the McGill pain questionnaire. Pain localization, supplemental analgesic consumption, vital signs, and side effects were recorded for 24 h.

Results

Neither intraperitoneal nor interpleural morphine produced significant analgesia after laparoscopic cholecystectomy (P > 0.05, Kruskal-Wallis test), whereas interpleural bupivacaine was effective (P < 0.05, Kruskal-Wallis test, up to 6 h postoperatively) but not intraperitoneal bupivacaine (P > 0.05, Kruskal-Wallis test). Shoulder pain was not prevalent in the majority of patients during the first 6 h. By 24 h, about half of the patients complained of shoulder pain, which was rated "low" by about one-third of all patients. No significant side effects occurred.

Conclusions

Interpleural bupivacaine (0.25%) produces analgesia after laparoscopic cholecystectomy. We attribute the lack of effect of intraperitoneal injections to the small dose and to a rapid dilution within the peritoneal cavity. The fact that interpleural morphine (0.005%) is ineffective may be due to an intact perineurial barrier in the noninflamed pleural cavity, which restricts the transperineurial passage of morphine to opioid receptors on intercostal nerves.
Intravenous Versus Epidural Administration of Hydromorphone
Authors: Liu Spencer , Carpenter Randall L. , Mulroy Michael F. , Weissman Robert M. , McGill Theodore J. , Rupp Stephen M. , Allen Hugh W.
Published: November 2003

Background

It remains unclear whether epidural administration of hydromorphone results in spinal analgesia or clinical benefit when compared with intravenous administration. Therefore, we undertook this study to determine whether epidural administration of hydromorphone resulted in decreased opioid requirement, improved analgesia, reduced side effects, more rapid return of gastrointestinal function, or shorter duration of hospital stay than intravenous administration.

Methods

Sixteen patients undergoing radical retropubic prostatectomy were randomized in a double-blind manner to receive either intravenous or epidural hydromorphone via patient-controlled analgesia (PCA) for postoperative analgesia. All patients underwent a standardized combined epidural and general anesthetic and all received ketorolac for 72 h postoperatively. To decrease variability, patients were cared for according to a standardized protocol and were deemed ready for discharge according to prospectively defined criteria.

Results

Patients in the intravenous PCA group required approximately twice as much opioid than the epidural PCA group (P < 0.008), but there were no differences between groups in pain scores or patient satisfaction. Epidural administration resulted in a greater incidence of pruritus (P = 0.02). Gastrointestinal function recovered quickly in all patients with little variation, and there were no differences between groups. All patients were deemed ready for discharge by the third postoperative day, and removal of surgical drains was the last discharge criterion reached in all patients.

Conclusions

Our results indicate that epidural administration of hydromorphone results in spinally mediated analgesia. However, epidural administration did not provide significant benefits in terms of postoperative analgesia, recovery of gastrointestinal function, or duration of hospitalization. Furthermore, we suggest that radical retropubic prostatectomy no longer be used as a model to assess the effects of analgesic technique on postoperative recovery, because control of discharge criteria revealed that hospital discharge was primarily dependent on removal of surgical drains.
Isoflurane and the Pulmonary Vascular Pressure-Flow Relation at Baseline and during Sympathetic α- and β-Adrenoreceptor Activation in Chronically Instrumented Dogs
Authors: Lennon Paul F. , Murray Paul A.
Published: November 2003

Background

The extent to which isoflurane anesthesia alters systemic vascular regulation has received considerable attention. In contrast, the pulmonary vascular effects of isoflurane have not been elucidated. Our initial objective was to investigate the net effect of isoflurane on the baseline left pulmonary vascular pressure-flow (LPQ) relation compared with values measured in the conscious state. In addition, we assessed the extent to which isoflurane alters the pulmonary vascular responses to sympathetic alpha- and beta-adrenoreceptor activation.

Methods

Twelve conditioned mongrel dogs were chronically instrumented to measure the LPQ relation. LPQ plots were generated by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure--left atrial pressure) and left pulmonary blood flow during gradual (approximately 1 min) inflation of a hydraulic occluder implanted around the right main pulmonary artery. LPQ plots were generated at baseline in the conscious and isoflurane-anesthetized states (n = 12). The pulmonary vascular dose-response relation to the sympathetic alpha-adrenoreceptor agonist phenylephrine also was investigated in conscious and isoflurane-anesthetized dogs (n = 6). Finally, after preconstriction with the thromboxane analogue U46619, the dose-response relation to the sympathetic beta-adrenoreceptor agonist isoproterenol was assessed in the conscious and isoflurane-anesthetized states (n = 8).

Results

Compared with values measured in the conscious state, isoflurane anesthesia had no net effect on the baseline LPQ relation. The magnitude of the pulmonary vasoconstrictor response to phenylephrine observed in conscious dogs was not altered during isoflurane anesthesia. In contrast, the pulmonary vasodilator response to isoproterenol was markedly potentiated (P < 0.01) during isoflurane anesthesia compared with that in the conscious state.

Conclusions

These results indicate that isoflurane does not exert a net vasodilator influence on the pulmonary circulation at baseline. In contrast to the systemic circulation, the pulmonary vasoconstrictor response to sympathetic alpha-adrenoreceptor activation is maintained during isoflurane anesthesia. Surprisingly, the pulmonary vasodilator response to sympathetic beta-adrenoreceptor activation is actually potentiated during isoflurane. Thus, isoflurane anesthesia has differential effects on the canine pulmonary vascular responses to sympathetic alpha- and beta-adrenoreceptor activation.
Influence of Gas Composition on Recurrence of Atelectasis after a Reexpansion Maneuver during General Anesthesia
Authors: Rothen Hans Ulrich , Sporre Bengt , Engberg Greta , Wegenius Goran , Hogman Marieann , Hedenstierna Goran
Published: November 2003

Background

Atelectasis, an important cause of impaired gas exchange during general anesthesia, may be eliminated by a vital capacity maneuver. However, it is not clear whether such a maneuver will have a sustained effect. The aim of this study was to determine the impact of gas composition on reappearance of atelectasis and impairment of gas exchange after a vital capacity maneuver.

Methods

A consecutive sample of 12 adults with healthy lungs who were scheduled for elective surgery were studied. Thirty minutes after induction of anesthesia with fentanyl and propofol, the lungs were hyperinflated manually up to an airway pressure of 40 cmH2O. FIO2 was either kept at 0.4 (group 1, n = 6) or changed to 1.0 (group 2, n = 6) during the recruitment maneuver. Atelectasis was assessed by computed tomography. The amount of dense areas was measured at end-expiration in a transverse plane at the base of the lungs. The ventilation-perfusion distributions (VA/Q) were estimated with the multiple inert gas elimination technique. The static compliance of the total respiratory system (Crs) was measured with the flow interruption technique.

Results

In group 1 (FIO2 = 0.4), the recruitment maneuver virtually eliminated atelectasis for at least 40 min, reduced shunt (VA/Q < 0.005), and increased at the same time the relative perfusion to poorly ventilated lung units (0.005 < VA/Q < 0.1; mean values are given). The arterial oxygen tension (PaO2) increased from 137 mmHg (18.3 kPa) to 163 mmHg (21.7 kPa; before and 40 min after recruitment, respectively; P = 0.028). In contrast to these findings, atelectasis recurred within 5 min after recruitment in group 2 (FIO2 = 1.0). Comparing the values before and 40 min after recruitment, all parameters of VA/Q were unchanged. In both groups, Crs increased from 57.1/55.0 ml.cmH2O-1 (group 1/group 2) before to 70.1/67.4 ml.cmH2O-1 after the recruitment maneuver. Crs showed a slow decrease thereafter (40 min after recruitment: 61.4/60.0 ml.cmH2O-1), with no difference between the two groups.

Conclusions

The composition of inspiratory gas plays an important role in the recurrence of collapse of previously reexpanded atelectatic lung tissue during general anesthesia in patients with healthy lungs. The reason for the instability of these lung units remains to be established. The change in the amount of atelectasis and shunt appears to be independent of the change in the compliance of the respiratory system.
Analysis of Statistical Tests to Compare Visual Analog Scale Measurements among Groups
Authors: Dexter Franklin , Chestnut David H.
Published: November 2003

Background

A common type of study performed by anesthesiologists determines the effect of an intervention on pain reported by groups of patients. The goal of this study was to evaluate the effectiveness of t, analysis of variance (ANOVA), Mann-Whitney, and Kruskal-Wallis tests to compare visual analog scale (VAS) measurements between two or among three groups of patients. These results may be particularly helpful during the design of studies that measure pain with a VAS.

Methods

One VAS measurement was obtained from each of 480 nulliparous women in labor who were receiving oxytocin (149), nalbuphine (159), or epidural bupivacaine (172). Multiple simulated samples were then drawn from these data. These simulated samples were used in computer simulations of clinical trials comparing VAS measurements among groups. t and ANOVA tests were performed before and after an arcsin transformation was used, to make the data closer to a normal distribution. VAS measurements were also compared after they were divided into five ranked categories.

Results

The statistical distributions of VAS measurements were not normal (P < 10(-7)). Arcsin transformation made the distributions closer to normal distributions. Nevertheless, no statistical test incorrectly suggested that a difference existed among groups, when there was no difference, more often than the expected rate. t or ANOVA tests had a slightly greater statistical power than the other tests to detect differences among groups. Because arcsin transformation both decreased differences among means and reduced the variance to a lesser extent, it decreased power to detect differences among groups. Statistical power to detect differences among groups was not less for a five-category VAS than for a continuous VAS.

Conclusions

We conclude that t and ANOVA, without an accompanying arcsin transformation, are good tests to find differences in VAS measurements among groups.
Weekly Ventilator Circuit Changes
Authors: Hess Dean , Burns Edward , Romagnoli David , Kacmarek Robert M.
Published: November 2003

Background

Mechanical ventilator circuits are commonly changed at 48-h intervals. This frequency may be unnecessary because ventilator-associated pneumonia often results from aspiration of pharyngeal secretions and not from the ventilator circuit. We compared the ventilator-associated pneumonia rates and costs associated with 48-h and 7-day circuit changes.

Methods

Ventilator circuits were changed at 48-h intervals during the control period (November 1992 to April 1993) and at 7-day intervals during the study period (June 1993 to November 1993). Nosocomial pneumonias were prospectively identified using the criteria of the Centers for Disease Control and Prevention. The annual cost difference of changing circuits at 48-h and 7-day intervals was calculated using the distribution of ventilator days for the control and study periods.

Results

There were 1,708 patients, 9,858 ventilator days, and a pneumonia rate of 9.64 per 1,000 ventilator days in the control group (48-h circuit changes). There were 1,715 patients, 9,160 ventilator days, and 8.62 pneumonias per 1,000 ventilator days when circuits were changed at 1-week intervals (study group). Using a logistic regression model, there were significantly greater odds of developing a ventilator-associated pneumonia in surgical patients (odds ratio 1.77, P = 0.02) and patients in critical care units (odds ratio 1.54, P = 0.05), but no significant risk of ventilator-associated pneumonia in patients in whom circuits were changed at 1-week intervals (odds ratio 0.82, P = 0.22). Changing circuits at 7-day intervals resulted in a 76.6% ($111,530) reduction in the annual cost for materials and salaries.

Conclusions

We found no difference in pneumonia rates with ventilator circuit changes at 48-h and 7-day intervals. Ventilator circuits can be safely changed at weekly intervals, resulting in large cost savings.