bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Effects of Intrathecally Administered Morphine and Its Interaction with Cholecystokinin-B Antagonist on Thermal Hyperalgesia following Two Models of Experimental Mononeuropathy in the Rat
Authors: Yamamoto Tatsuo , Sakashita Yoshihiko
Published: November 2003

Background

Cholecystokinin-B receptor activation has been reported to reduce morphine analgesia. Neuropathic pain is thought to be relatively refractory to opioids. One possible mechanisms for a reduced effect of morphine on neuropathic pain is the induction of cholecystokinin in the spinal cord by nerve injury. The authors evaluated the role of the spinal cholecystokinin-B receptor on morphine analgesia in two rat neuropathic pain models: chronic constriction injury and partial sciatic nerve injury.

Methods

A chronic constriction injury is created by placing four loosely tied ligatures around the right sciatic nerve. A partial sciatic nerve injury was created by tight ligation of one third to one half of the right sciatic nerve. All drugs were injected intrathecally 7 and 11 days after the nerve injury. The effect of the drugs was reflected in the degree of paw withdrawal latency to thermal nociceptive stimulation. The paw withdrawal latencies of injured and uninjured paws were measured 5, 15, 30, and 60 min after the drugs were injected.

Results

In the chronic constriction injury model, intrathecal morphine increased the paw withdrawal latencies of injured and uninjured paws. PD135158, a cholecystokinin-B receptor antagonist, potentiated the analgesic effect of morphine on injured and uninjured paws. In the partial sciatic nerve injury model, the effect of morphine on the injured paw was less potent than that on the uninjured paw, and PD135158 potentiated the morphine analgesia in the uninjured paw and had only a minor effect on the morphine analgesia in the injured paw.

Conclusions

The effectiveness of morphine for thermal hyperalgesia after nerve injury depends on the type of nerve injury. The role of the cholecystokinin-B receptor in morphine analgesia in thermal hyperalgesia after nerve injury also depends on the type of nerve injury.
NOS Inhibitors Decrease Hypoxia-induced ATP Reductions in Respiring Cerebrocortical Slices
Authors: Litt Lawrence , Espanol Maryceline T. , Hasegawa Koh , Chang Lee-Hong , Gregory George A. , James Thomas L. , Beal Flint M. , Chan Pak H.
Published: November 2003

Background

Excess neuronal nitric oxide (NO) production might cause adenosine triphosphate loss and cellular damage in hypoxic brain parenchyma. 31P nuclear magnetic resonance spectroscopy was used to study hypoxic intracellular responses in perfused respiring cerebrocortical slices, in which NO scavenging by hemoglobin is absent, during NO synthase blockade and NO augmentation.

Methods

Adenosine triphosphate concentrations were monitored at 4.7 Tesla in respiring slices before, during, and after 60 min of hypoxia (oxygen tension < 5 mmHg). Slices were not treated or were pretreated with 27 microM L-nitroarginine methyl ester (L-NAME), 27 microM 7-nitroindozole (7-NI), or 27 microM L-nitroarginine. Nitrotyrosine:tyrosine ratios of slice extracts were measured using high-performance liquid chromatography. Cresyl violet-stained sections (2 microm) from random slices were examined histologically.

Results

After 60 min of hypoxia, adenosine triphosphate decreased to < or = 3, < or = 3, 65 +/- 6, and 25 +/- 4% of control in slices that were untreated or treated with L-nitroarginine, L-NAME, and 7-NI, respectively. After 120 min of hyperoxic recovery, adenosine triphosphate levels returned to control values in slices pretreated with L-NAME and 7-NI, but to only 30% of control in untreated or L-nitroarginine-treated slices. Nitric oxide donors administered during posthypoxic recovery partially antagonized the adenosine triphosphate recovery found with L-NAME and 7-NI. Nitric oxide synthase activity in slice homogenates, assayed via conversion of L-arginine to citrulline, was < or = 2% of control after all inhibitory treatments. The nitrotyrosine:tyrosine ratio increased by 52% in slices treated with 7-NI and by 200-300% in all other groups. Pretreatment with L-NAME and 7-NI reduced histologic evidence of cell swelling.

Conclusion

Neuronal NO is associated with rapid adenosine triphosphate reductions and peroxynitrite formation in acutely hypoxic cerebrocortical slices.
Brain Injury after Cerebral Arterial Air Embolism in the Rabbit as Determined by Triphenyltetrazolium Staining
Authors: Hindman Bradley J. , Dexter Franklin , Subieta Alberto , Smith Tom , Cutkomp Johann
Published: November 2003

Background

Microscopic cerebral arterial air embolism (CAAE) occurs commonly during cardiac surgery and causes acute and chronic nonfocal neurologic dysfunction. Nevertheless, most neuroimaging studies do not detect brain injury after cardiac surgery. Using a rabbit model, the authors hypothesized they could detect and quantitate severe brain injury and infarction 24 h after microscopic CAAE using the vital stain triphenyltetrazolium chloride.

Methods

Experiments were conducted in methohexital anesthetized New Zealand white rabbits. Surgical shams (n = 5) underwent surgery but had no neurologic insult. Positive controls (n = 3) received 200 microl/kg of intracarotid air. Other animals were randomized to receive either 50 microl/kg intracarotid air, which produces microscopic CAAE (n = 18), or 300 microl intracarotid saline (control, n = 18). Outcomes included somatosensory evoked potential amplitude at 90 min, neurologic impairment score at 4 and 24 h (0 [normal] to 99 [coma]), and percentage of nonstaining brain at 24 h using color-discrimination image analysis. Severely injured or infarcted brain does not stain with triphenyltetrazolium chloride.

Results

Surgical shams had little neurologic impairment and a small amount of nonstaining brain at 24 h (5.2 +/- 2.4%; mean +/- SD). Positive controls had profound neurologic impairment and large amounts of nonstaining brain (40-97%). Ninety-minute somatosensory evoked potential amplitude was less in animals receiving 50 microl/kg air versus saline: 38 +/- 28% versus 102 +/- 32%, respectively, P < 1 x 10(-7). Neurologic impairment scores were greater in animals receiving 50 microl/kg air versus saline: at 4 h, 43 +/- 16 versus 23 +/- 9, P < 1 x 10(-7); at 24 h, 24 +/- 12 versus 15 +/- 8, P = 0.013. Nevertheless, there was no difference between 50 microl/kg air and saline in nonstaining brain: 5.5 +/- 2.9% versus 6.8 +/- 5.4%, P = 0.83.

Conclusions

Neurologic injury after CAAE is dose-dependent. Although microscopic CAAE causes somatosensory evoked potential abnormalities and neurologic dysfunction, severe cerebral injury or infarction is not present at 24 h. The author's findings are consistent with clinical imaging studies that suggest microscopic CAAE causes neurologic dysfunction even though overt infarction is absent.
The Influence of Age on Propofol Pharmacodynamics
Authors: Schnider Thomas W. , Minto Charles F. , Shafer Steven L. , Gambus Pedro L. , Andresen Corina , Goodale David B. , Youngs Elizabeth J.
Published: November 2003

Background

The authors studied the influence of age on the pharmacodynamics of propofol, including characterization of the relation between plasma concentration and the time course of drug effect.

Methods

The authors evaluated healthy volunteers aged 25-81 yr. A bolus dose (2 mg/kg or 1 mg/kg in persons older than 65 yr) and an infusion (25, 50, 100, or 200 microg x kg(-1) x min(-1)) of the older or the new (containing EDTA) formulation of propofol were given on each of two different study days. The propofol concentration was determined in frequent arterial samples. The electroencephalogram (EEG) was used to measure drug effect. A statistical technique called semilinear canonical correlation was used to select components of the EEG power spectrum that correlated optimally with the effect-site concentration. The effect-site concentration was related to drug effect with a biphasic pharmacodynamic model. The plasma effect-site equilibration rate constant was estimated parametrically. Estimates of this rate constant were validated by comparing the predicted time of peak effect with the time of peak EEG effect. The probability of being asleep, as a function of age, was determined from steady state concentrations after 60 min of propofol infusion.

Results

Twenty-four volunteers completed the study. Three parameters of the biphasic pharmacodynamic model were correlated linearly with age. The plasma effect-site equilibration rate constant was 0.456 min(-1). The predicted time to peak effect after bolus injection ranging was 1.7 min. The time to peak effect assessed visually was 1.6 min (range, 1-2.4 min). The steady state observations showed increasing sensitivity to propofol in elderly patients, with C50 values for loss of consciousness of 2.35, 1.8, and 1.25 microg/ml in volunteers who were 25, 50, and 75 yr old, respectively.

Conclusions

Semilinear canonical correlation defined a new measure of propofol effect on the EEG, the canonical univariate parameter for propofol. Using this parameter, propofol plasma effect-site equilibration is faster than previously reported. This fast onset was confirmed by inspection of the EEG data. Elderly patients are more sensitive to the hypnotic and EEG effects of propofol than are younger persons.
Augmentation of the Rocuronium-induced Neuromuscular Block by the Acutely Administered Phenytoin
Authors: Spacek Anna , Nickl Stephan , Neiger Franz X. , Nigrovic Vladimir , Ullrich Odo-Winfried , Weindlmayr-Goettel Marta , Schwall Barbara , Taeger Kai , Kress Hans Georg
Published: November 2003

Background

The effects of an acute administration of phenytoin on the magnitude of the rocuronium-induced neuromuscular block were evaluated.

Methods

Twenty patients (classified as American Society of Anesthesiologists physical status I or II) scheduled for craniotomy were studied: 15 received phenytoin during operation (10 mg/kg), and the others served as controls. Anesthesia was induced with thiopental and fentanyl and maintained with nitrous oxide (65%) in oxygen and end-tidal isoflurane (1%). The ulnar nerve was stimulated supramaximally and the evoked electromyography was recorded using a neuromuscular transmission monitor. Continuous infusion of rocuronium maintained the neuromuscular block with first twitch (T1) between 10 and 15% for 45 min before the start of an infusion of either phenytoin or NaCl 0.9%. Twitch recordings continued for 60 min thereafter. Arterial blood samples were collected at the predefined time points (four measurements before and four after the start of the infusion) to determine the concentrations of phenytoin and rocuronium and the percentage of rocuronium bound to plasma proteins.

Results

The first twitch produced by an infusion of rocuronium remained constant during the 15 min before and the 60 min after the start of the saline infusion. After the phenytoin infusion, the twitch decreased progressively, but the plasma concentrations and the protein-bound fraction of rocuronium did not change.

Conclusion

Phenytoin acutely augments the neuromuscular block produced by rocuronium without altering its plasma concentration or its binding to plasma proteins.
L-Arginine Infusion Dilates Coronary Vasculature in Patients Undergoing Coronary Bypass Surgery
Authors: Wallace Arthur W. , Ratcliffe Mark B. , Galindez Daniel , Kong James S.
Published: November 2003

Background

Nitric oxide-dependent factors (serotonin, activated platelets, acetylcholine) cause vasodilation in normal coronary arteries but vasoconstrict atherosclerotic vessels. This experiment tested the hypothesis that intravenous systemic infusions of L-arginine, a precursor for nitric oxide production, dilate the coronary vascular bed of patients undergoing coronary artery bypass graft surgery.

Methods

Twenty patients scheduled for coronary artery bypass graft surgery surgery were studied in a prospective, blinded, randomized clinical trial. Saphenous vein graft blood flow was measured with a transit time flow probe, and coronary vascular resistance was calculated. After weaning from bypass, patients were given a venous infusion (placebo or 10% arginine hydrochloride [30 g]) over 15 min. Arterial blood samples for the determination of L-arginine and L-citrulline levels were drawn before, 10 min after starting infusion, and 10 min after end of infusion.

Results

The placebo group experienced an increase in mean arterial pressure and coronary vascular resistance and a decrease in graft blood flow. Patients in the L-arginine group maintained their baseline values. Mean arterial pressure (L-arginine, 88+/-17 to 92+/-13 mmHg vs. placebo, 80+/-12 to 92+/-9 mmHg, P = 0.021), coronary vascular resistance (L-arginine, 97,000+/-60,000 to 99,600+/-51,000 dynes x s x cm(-5) vs. placebo, 81,000+/-69,000 to 117,000+/-64,000 dynes x s x cm(-5), P = 0.05), and graft blood flow (L-arginine, 55+/-25 to 50+/-19 ml/min vs. placebo, 60+/-34 to 46+/-18, P = 0.05) remained more stable in the L-arginine-treated patients.

Conclusions

Systemic L-arginine infusion reduced postbypass coronary vasoconstriction. There were no adverse events associated with the drug infusion.
The effect of Pyrogen Administration on Sweating and Vasoconstriction Thresholds during Desflurane Anesthesia
Authors: Lenhardt Rainer , Negishi Chiharu , Sessler Daniel I. , Ozaki Makoto , Ettinger Katharine , Bastanmehr Hiva , Lobo Errol
Published: November 2003

Background

General anesthetics increase the sweating-to-vasoconstriction interthreshold range (temperatures not triggering thermoregulatory defenses), whereas fever is believed to only increase the setpoint (target core temperature). However, no data characterize thresholds (temperatures triggering thermoregulatory defenses) during combined anesthesia and fever. Most likely, the combination produces an expanded interthreshold range around an elevated setpoint. The authors therefore tested the hypothesis that thermoregulatory response thresholds during the combination of fever and anesthesia are simply the linear combination of the thresholds resulting from each intervention alone.

Methods

The authors studied eight healthy male volunteers. Fever was induced on the appropriate days by intravenous injection of 30 IU/g human recombinant interleukin 2 (IL-2), followed 2 h later by an additional 70 IU/g. General anesthesia consisted of desflurane 0.6 minimum alveolar concentration (MAC). The volunteers were randomly assigned to the following groups: (1) control (no desflurane, no IL-2); (2) IL-2 alone; (3) desflurane alone; and (4) desflurane plus IL-2. During the fever plateau, volunteers were warmed until sweating was observed and then cooled to vasoconstriction. Sweating was evaluated from a ventilated capsule and vasoconstriction was quantified by volume plethysmography. The tympanic membrane temperatures triggering significant sweating and vasoconstriction identified the respective response thresholds. Data are presented as the mean +/- SD; P < 0.05 was considered significant.

Results

The interthreshold range was near 0.40 degrees C on both the control day and during IL-2 administration alone. On the IL-2 alone day, however, the interthreshold range was shifted to higher temperatures. The interthreshold range increased significantly during desflurane anesthesia to 1.9+/-0.6 degrees C. The interthreshold range during the combination of desflurane and IL-2 was 1.2+/-0.6 degrees C, which was significantly greater than on the control and IL-2 alone days. However, it was also significantly less than during desflurane alone.

Conclusion

The combination of desflurane and IL-2 caused less thermoregulatory inhibition than would be expected based on the effects of either treatment alone. Fever-induced activation of the sympathetic nervous system may contribute by compensating for a fraction of the anesthetic-induced thermoregulatory impairment.
Comparison of Ropivacaine and Lidocaine for Intravenous Regional Anesthesia in Volunteers
Authors: Chan Vincent W. S. , Weisbrod Mitchell J. , Kaszas Zsuzsanna , Dragomir Camelia
Published: November 2003

Background

Ropivacaine may be useful for intravenous regional anesthesia, but its anesthetic effectiveness and toxicity have not been evaluated.

Methods

Two doses of ropivacaine (1.2 and 1.8 mg/kg) and one dose of lidocaine (3 mg/kg) were compared for intravenous regional anesthesia in 15 volunteers. An arm tourniquet was inflated for 30 min after injection and then deflated in two cycles. Sensory block was measured by response to touch, cold, pinprick, and transcutaneous electric stimulation, and motor function was measured by hand grip strength and muscle power. Median, ulnar, radial, and musculocutaneous nerve functions were tested before local anesthetic injection and then at 5-min intervals until blocks resolved. The plasma ropivacaine and lidocaine concentrations were determined from arterial and venous blood samples drawn from the unanesthetized arm.

Results

Sensory and motor blocks were complete within 25 min and 30 min, respectively, in all three treatment groups. However, recovery of sensory and motor block after tourniquet release was slowest in the high-dose ropivacaine group. Anesthesia to pinprick and transcutaneous electric stimulation was sustained in all the volunteers in the high-dose ropivacaine group for 55 min and 85 min, respectively, whereas complete recovery was observed in the lidocaine group (P = 0.008) and partial recovery in the low-dose ropivacaine group (P < 0.05) during the same period. Motor block also was sustained in the high-dose ropivacaine group for 70 min, which was significantly longer than in the lidocaine group (P < 0.05). All volunteers (five of five) given lidocaine and one volunteer given high-dose ropivacaine reported light-headedness and hearing disturbance during tourniquet release when the arterial plasma lidocaine and ropivacaine concentrations were 4.7+/-2.1 microg/ml (mean) and 2.7 micro/ml, respectively.

Conclusion

Compared with lidocaine, intravenous regional anesthesia with ropivacaine appears to be comparable but has longer-lasting residual anesthesia.
Shivering and Shivering-like Tremor during Labor with and without Epidural Analgesia
Authors: Panzer Oliver , Ghazanfari Naghme , Sessler Daniel I. , Yucel Yuksel , Greher Manfred , Akca Ozan , Donner Andrew , Germann Peter , Kurz Andrea
Published: November 2003

Background

Effective treatment and prevention of hyperthermia and shivering-like tremor during labor is hindered by a poor understanding of their causes. The authors sought to identify the incidence of nonthermoregulatory shivering-like tremor and the factors associated with this activity.

Methods

The authors studied women in spontaneous full-term labor who chose epidural analgesia (n = 21) or opioid sedation (n = 31). Shivering-like tremor and sweating were evaluated by observation. Core temperature was recorded in the external auditory canal using a compensated infrared thermometer. Arteriovenous shunt tone was evaluated with forearm minus fingertip skin temperature gradients; gradients less than 0 were considered evidence of vasodilation. Tremor was considered nonthermoregulatory when core temperature exceeded 37 degrees C and the arms were vasodilated. Pain was evaluated using a visual analog scale.

Results

Shivering-like tremor was observed in 18% of 290, 30-min data-acquisition epochs before delivery. The patients were both normothermic and vasodilated during 15% of these epochs. Shivering was observed in 16% of 116 postdelivery epochs and was nonthermoregulatory in 28%. Sweating was observed in 30% of predelivery epochs, and the patients were both hypothermic and vasoconstricted during 12%. The mean core temperature in patients given epidural analgesia was approximately 0.2 degrees C greater than in those given sedation. Hyperthermia was observed during 10 epochs (38.4+/-0.3 degrees C) during epidural analgesia and during 10 epochs (38.4+/-0.3 degrees C) with sedation. The patients were vasoconstricted in more than 50% of these epochs in each group. Multivariate mixed-effects modeling identified high pain scores and vasoconstriction as significant predictors of shivering. There were no predictors for shivering epochs in patients who were simultaneously normothermic and vasodilated. Significant predictors of sweating were time before delivery, high pain scores, hypothermia with vasoconstriction, high thermal comfort, and low mean skin temperature. There were no predictors for sweating epochs in patients who were simultaneously hypothermic and vasoconstricted.

Conclusions

This study confirms the clinical impression that some peripartum shivering-like tremor is nonthermoregulatory. The authors also identified nonthermoregulatory sweating. These data indicate that shivering-like tremor and sweating in the peripartum period is multifactorial.
Pharmacokinetics of ε-aminocaproic Acid in Patients Undergoing Aortocoronary Bypass Surgery
Authors: Butterworth John , James Robert L. , Lin Yonggu , Prielipp Richard C. , Hudspeth Allen S.
Published: November 2003

Background

Epsilon-aminocaproic acid (EACA) is commonly infused during cardiac surgery using empiric dosing schemes. The authors developed a pharmacokinetic model for EACA elimination in surgical patients, tested whether adjustments for cardiopulmonary bypass (CPB) would improve the model, and then used the model to develop an EACA dosing schedule that would yield nearly constant EACA blood concentrations.

Methods

Consenting patients undergoing elective coronary artery surgery received one of two loading doses of EACA, 30 mg/kg (group I, n = 7) or 100 mg/kg (group II, n = 6) after CPB, or (group III) a 100 mg/kg loading dose before CPB and a 10 mg x kg(-1) x h(-1) maintenance infusion continued for 4 h during and after CPB (n = 7). Two patients with renal failure received EACA in the manner of group III. Blood concentrations of EACA, measured by high-performance liquid chromatography, were subjected to mixed-effects pharmacokinetic modeling.

Results

The EACA concentration data were best fit by a model with two compartments and corrections for CPB. The elimination rate constant k10 fell from 0.011 before CPB to 0.0006 during CPB, returning to 0.011 after CPB. V1 increased 3.8 l with CPB and remained at that value thereafter. Cl1 varied from 0.08 l/min before CPB to 0.007 l/min during CPB and 0.13 l/min after CPB. Cl2 increased from 0.09 l/min before CPB to 0.14 l/min during and after CPB. Two patients with renal failure demonstrated markedly reduced clearance. Using their model, the authors predict that an EACA loading infusion of 50 mg/kg given over 20 min and a maintenance infusion of 25 mg x kg(-1) x h(-1) would maintain a nearly constant target concentration of 260 microg/ml.

Conclusions

EACA clearance declines and volume of distribution increases during CPB. The authors' model predicts that more stable perioperative EACA concentrations would be obtained with a smaller loading dose (50 mg/kg given over 20 min) and a more rapid maintenance infusion (25 mg x kg(-1) x h(-1)) than are typically employed.
Neurokinin-1 Receptors Are Involved in Behavioral Responses to High-intensity Heat Stimuli and Capsaicin-induced Hyperalgesia in Mice
Authors: Mansikka Heikki , Shiotani Masako , Winchurch Richard , Raja Srinivasa N.
Published: November 2003

Background

The neurokinin-1 (NK-1) receptor and its ligand, substance P, are thought to play important roles in nociception and hyperalgesia. This study evaluated the role of the NK-1 receptor in processing noxious stimuli in normal and inflammatory states.

Methods

Behavioral responses to heat and mechanical and chemical stimuli were studied in NK-1 receptor knockout mice and wild-type control mice. Thermal nociception was evaluated by measuring paw lick or jump latencies to hot plate (52, 55, and 58 degrees C) and paw withdrawal latencies to radiant heat applied to the hind paws. Mechanical nociception was measured by von Frey monofilament applications to the hind paws. Intraplantar capsaicin-induced (10 microg/20 microl) paw licking and mechanical and heat hyperalgesia were compared in NK-1 knockout and wild-type mice.

Results

Withdrawal responses to radiant heat (4.3+/-0.18 s for knockout and 4.4+/-0.8 s for wild-type mice) and von Frey monofilaments were similar in knockout and wild-type mice. In the hot plate test, increasing the hot plate temperature from 52 degrees C to 58 degrees C resulted in a decrease in the response latency in the wild-type mice (30.4+/-17.5 s to 15.2+/-6.8 s, P < 0.05), whereas in the knockout mice the response latencies remained constant (28.2+/-19.8 s to 29+/-15.1 s, not significant). Capsaicin-induced paw licking (14.5+/-12.8 s for knockout and 41.3+/-37.3 s for wild-type mice, P < 0.05) and mechanical and heat hyperalgesia were attenuated in the knockout mice.

Conclusion

NK-1 receptors contribute to the withdrawal responses to high-intensity heat stimuli and to capsaicin-induced mechanical and heat hyperalgesia.
Interaction of Halogenated Anesthetics with Dobutamine in Rat Myocardium
Authors: Gueugniaud Pierre-Yves , Hanouz Jean-Luc , Martino Jean-Marc , Lecarpentier Yves , Coriat Pierre , Riou Bruno
Published: November 2003

Background

Halogenated anesthetics potentiate the positive inotropic effects of alpha- and beta-adrenoceptor stimulations, but their interactions with dobutamine remain unknown.

Methods

The effects of halothane, isoflurane, sevoflurane, and desflurane (1 and 2 minimum alveolar concentration) on the inotropic responses induced by dobutamine (10(-8)-10(-4) M) were studied in rat left ventricular papillary muscles in vitro. Inotropic effects were studied under low (isotony) and high (isometry) loads. The authors also studied the lusitropic effects in isotonic (R1) and isometric (R2) conditions. Data are the mean percentage of baseline +/- SD.

Results

Dobutamine induced a positive inotropic effect (active isometric force: 185+/-36%, P < 0.001) and a positive lusitropic effect under low load (R1: 78+/-9%, P < 0.001), but not under high load (R2: 95+/-21%, not significant). Halothane, isoflurane, and sevoflurane did not modify the positive inotropic effect of dobutamine. Even in the presence of alpha-adrenoceptor blockade, isoflurane did not potentiate the positive inotropic effect of dobutamine. Desflurane significantly enhanced the positive inotropic effect of dobutamine (active isometric force: 239+/-35%, P < 0.001), but this potentiation was abolished by pretreatment with reserpine. In contrast to halothane, isoflurane, sevoflurane, and desflurane did not significantly modify the lusitropic effects of dobutamine.

Conclusions

Halogenated anesthetics, except desflurane, did not modify the positive inotropic effects of dobutamine. Desflurane enhanced the positive inotropic effect of dobutamine, but this effect was related to the desflurane-induced release in intramyocardial catecholamine stores.
Effects of Halothane and Isoflurane on Fast and Slow Inactivation of Human Heart hH1a Sodium Channels
Authors: Stadnicka Anna , Kwok Wai-Meng , Hartmann Hali A. , Bosnjak Zeljko J.
Published: November 2003

Background

Cloning and heterologous expression of ion channels allow biophysical and molecular studies of the mechanisms of volatile anesthetic interactions with human heart sodium channels. Volatile anesthetics may influence the development of arrhythmias arising from cardiac sodium channel dysfunction. For that reason, understanding the mechanisms of interactions between these anesthetics and cardiac sodium channels is important. This study evaluated the mechanisms of volatile anesthetic actions on the cloned human cardiac sodium channel (hH1a) alpha subunit.

Methods

Inward sodium currents were recorded from human embryonic kidney (HEK293) cells stably expressing hH1a channels. The effects of halothane and isoflurane on current and channel properties were evaluated using the whole cell voltage-clamp technique.

Results

Halothane at 0.47 and 1.1 mM and isoflurane at 0.54 and 1.13 mM suppressed the sodium current in a dose- and voltage-dependent manner. Steady state activation was not affected, but current decay was accelerated. The voltage dependence of steady state fast and slow inactivations was shifted toward more hyperpolarized potentials. The slope factor of slow but not fast inactivation curves was reduced significantly. Halothane increased the time constant of recovery from fast inactivation. The recovery from slow inactivation was not affected significantly by either anesthetic.

Conclusions

In a heterologous expression system, halothane and isoflurane interact with the hH1a channels and suppress the sodium current. The mechanisms involve acceleration of the transition from the open to the inactivated state, stabilization of the fast and slow inactivated states, and prolongation of the inactivated state by delayed recovery from the fast inactivated to the resting state.
4-Chloro-m-cresol is a Trigger of Malignant Hyperthermia in Susceptible Swine
Authors: Wappler Frank , Scholz Jens , Fiege Marko , Kolodzie Kerstin , Kudlik Christiana , Weibhorn Ralf , Schulte am Esch Jochen
Published: November 2003

Background

4-Chloro-m-cresol (4-CmC) induces marked contractures in skeletal muscle specimens from individuals susceptible to malignant hyperthermia (MHS). In contrast, 4-CmC induces only small contractures in specimens from normal (MHN) patients. 4-CmC is a preservative within a large number of commercially available drug-preparations (e.g., insulin, heparin, succinylcholine), and it has been suggested that 4-CmC might trigger malignant hyperthermia. This study was designed to investigate the effects of 4-CmC in vivo and in vitro in the same animals.

Methods

After approval of the animal care committee, six Pietrain MHS and six control (MHN) swine were anesthetized with azaperone 4 mg/kg intramuscularly and metomidate 10 mg/kg intraperitoneally. After endotracheal intubation, lungs were mechanically ventilated (inspired oxygen fraction 0.3) and anesthesia was maintained with etomidate 2.5 mg x kg(-1) x h(-1) and fentanyl 50 microg x kg(-1) x h(-1). Animals were surgically prepared with arterial and central venous catheters for measurement of hemodynamic parameters and to obtain blood samples. Before exposure to 4-CmC in vivo, muscle specimens were excised for in vitro contracture tests with 4-CmC in concentrations of 75 and 200 microM. Subsequently, pigs were exposed to cumulative administration of 3, 6, 12, 24, and 48 mg/kg 4-CmC intravenously. If an unequivocal episode of malignant hyperthermia occurred, as indicated by venous carbon dioxide concentration > or = 70 mmHg, pH < or = 7.25, and an increase of temperature > or = 2 degrees C, the animals were treated with dantrolene, 3.5 mg/kg.

Results

All MHS swine developed malignant hyperthermia after administration of 4-CmC in doses of 12 or 24 mg/kg. Venous carbon dioxide concentration significantly increased and pH significantly decreased. Temperature increased in all MHS animals more than 2 degrees C. Blood lactate concentrations and creatine kinase levels were significantly elevated. All MHS swine were treated successfully with dantrolene. In contrast, no MHN swine developed signs of malignant hyperthermia. After receiving 4-CmC in a concentration of 48 mg/kg, however, all MHN animals died by ventricular fibrillation. The in vitro experiments showed that both concentrations of 4-CmC produced significantly greater contractures in MHS than in MHN specimens.

Conclusions

4-CmC is in vivo a trigger of malignant hyperthermia in swine. However, the 4-CmC doses required for induction of malignant hyperthermia were between 12 and 24 mg/kg, which is about 150-fold higher than the 4-CmC concentrations within clinically used preparations.
Is Outpatient Laparoscopic Cholecystectomy Safe and Cost-effective?
Authors: Fleisher Lee A. , Yee Kelvin , Lillemoe Keith D , Talamini Mark A. , Yeo Charles J. , Heath Roberta , Bass Eric , Snyder Douglas S. , Parker Stephen D.
Published: November 2003

Background

There is increasing pressure to perform traditional inpatient surgical procedures in an outpatient setting. The aim of the current trial was to determine the safety and cost savings of performing laparoscopic cholecystectomy in an outpatient setting using a "mock" outpatient setting.

Methods

Patients who were scheduled for laparoscopic cholecystectomy by four attending surgeons and for whom operating time was available in the outpatient center were studied. All patients received a standardized anesthetic, including ondansetron, and were discharged from the outpatient postanesthesia care unit if appropriate. At discharge, all patients were admitted to a clinical research center where they were observed in a "mock home" setting and monitored for complications that would have necessitated readmission. A decision analysis was created assuming all patients underwent outpatient surgery with either direct admission or discharge to home and readmission if complications developed.

Results

Of 99 patients who were enrolled in this study, 96 patients would have met the discharge criteria for home. No major complications were observed in these 96 patients. Eleven patients experienced postoperative nausea and vomiting, 3 of whom required an additional 24 h of hospital observation. In the decision model, the optimal strategy would be to perform the procedure on an outpatient basis and readmit patients only for complications, with an average baseline cost savings of $742/patient.

Conclusions

The results show that outpatient laparoscopic cholecystectomy is safe and cost-effective in selected patients, and that the mock home setting provides a means of studying the safety of transition of care.
Effects of Perioperative Analgesic Technique on the Surgical Outcome and Duration of Rehabilitation after Major Knee Surgery
Authors: Capdevila Xavier , Barthelet Yves , Biboulet Philippe , Ryckwaert Yves , Rubenovitch Josh , d'Athis Francoise
Published: November 2003

Background

Continuous passive motion after major knee surgery optimizes the functional prognosis but causes severe pain. The authors tested the hypothesis that postoperative analgesic techniques influence surgical outcome and the duration of convalescence.

Methods

Before standardized general anesthesia, 56 adult scheduled for major knee surgery were randomly assigned to one of three groups, each to receive a different postoperative analgesic technique for 72 h: continuous epidural infusion, continuous femoral block, or intravenous patient-controlled morphine (dose, 1 mg; lockout interval, 7 min; maximum dose, 30 mg/4 h). The first two techniques were performed using a solution of 1% lidocaine, 0.03 mg/ml morphine, and 2 microg/ml clonidine administered at 0.1 ml x kg(-1) x h(-1). Pain was assessed at rest and during continuous passive motion using a visual analog scale. The early postoperative maximal amplitude of knee flexion was measured during continuous passive motion at 24 h and 48 h and compared with the target levels prescribed by the surgeon. To evaluate functional outcome, the maximal amplitudes were measured again on postoperative day 5, at hospital discharge (day 7), and at 1- and 3-month follow-up examinations. When the patients left the surgical ward, they were admitted to a rehabilitation center, where their length of stay depended on prospectively determined discharge criteria

Results

The continuous epidural infusion and continuous femoral block groups showed significantly lower visual analog scale scores at rest and during continuous passive motion compared with the patient-controlled morphine group. The early postoperative knee mobilization levels in both continuous epidural infusion and continuous femoral block groups were significantly closer to the target levels prescribed by the surgeon than in the patient-controlled morphine group. On postoperative day 7, these values were 90 degrees (60-100 degrees)(median and 25th-75th percentiles) in the continuous epidural infusion group, 90 degrees (60-100 degrees) in the continuous femoral block group, and 80 degrees (60-100 degrees) in the patient-controlled morphine group (P < 0.05). The durations of stay in the rehabilitation center were significantly shorter: 37 days (range, 30-45 days) in the continuous epidural infusion group, 40 days (range, 31-60 days) in the continuous femoral block group, and 50 days (range, 30-80 days) in the patient-controlled morphine group (P < 0.05). Side effects were encountered more frequently in the continuous epidural infusion group.

Conclusion

Regional analgesic techniques improve early rehabilitation after major knee surgery by effectively controlling pain during continuous passive motion, thereby hastening convalescence.
Ultrasound-guided Internal Jugular Venous Cannulation in Infants
Authors: Verghese Susan T. , McGill Willis A. , Patel Ramesh I. , Sell Jeffrey E. , Midgley Frank M. , Ruttimann Urs E.
Published: November 2003

Background

Percutaneous cannulation of the internal jugular vein in infants is technically more difficult and carries a higher risk of carotid artery puncture than in older children and adults. In this prospective study, the authors tested their hypothesis that using an ultrasound scanner would increase the success of internal jugular cannulation and decrease the incidence of carotid artery puncture in infants.

Methods

After approval from the institutional review board and receipt of written informed parental consent, 95 infants scheduled for cardiac surgery were randomized prospectively into two groups. In the landmarks group, the patients' internal jugular veins were cannulated using the traditional method of palpation of carotid pulsation and identification of other anatomic landmarks. In the ultrasound group, cannulation was guided using an ultrasound scanner image. The cannulation time, number of attempts, success rate, and incidence of complications were compared for the two groups.

Results

There were no significant differences between the two groups with regard to weight, age, and American Society of Anesthesiologists physical status classification. The success rate was 100% in the ultrasound group, with no carotid artery punctures, and 77% in the landmarks group, with a 25% incidence of carotid artery punctures. Both differences were significant (P > 0.0004). The cannulation time was less, the number of attempts was fewer, and the failure rate was significantly lower in the ultrasound group than in the landmark group.

Conclusion

Ultrasonographic localization of the internal jugular vein was superior to the landmarks technique in terms of overall success, speed, and decreased incidence of carotid artery puncture.
Bupivacaine Augments Intrathecal Fentanyl for Labor Analgesia
Authors: Palmer Craig M. , Van Maren Gretchen , Nogami Wallace M. , Alves Diane
Published: November 2003

Background

fentanyl has been shown to be an effective analgesic for labor; this study investigated the analgesic effect of low-dose bpivacaine added to intrathecal fentanyl for labor analgesia

Methods

Ninety parturients in active labor who requested regional analgesia were randomized to receive an intrathecal injection of either fentanyl, 25 microg; bupivacaine, 1.25 mg, with fentanyl, 25 microg; or bupivacaine, 2.5 mg, with fentanyl, 25 microg, as part of a combined spinal-epidural technique. Visual analog pain scores were recorded before and at intervals after injection until the patient requested further analgesia. Maternal blood pressure and fetal heart rate were recorded before and at intervals after injection. Lower-extremity muscle strength was tested before and 30 min after injection; anesthetic level to cold sensation and the presence and severity of pruritus were recorded.

Results

Duration of analgesia was longer in the group receiving bupivacaine, 2.5 mg, and fentanyl, 25 microg, than the group receiving plain fentanyl (108 vs. 92 min; P < 0.05). Onset of analgesia was faster in both groups receiving bupivacaine compared with plain fentanyl (P < 0.05). No differences in muscle strength after injection were found in any group, although anesthetic levels to cold were documented in all patients in the bupivacaine groups, and 21 of 30 in the plain fentanyl group. Baseline fetal heart rates did not change after injection in any group, and maternal blood pressure was unchanged.

Conclusions

The addition of 2.5 mg isobaric bupivacaine to 25 microg fentanyl for intrathecal labor analgesia modestly increases duration and speeds onset of analgesia compared with plain intrathecal fentanyl.
Can Postoperative Nausea and Vomiting Be Predicted?
Authors: Sinclair David R. , Chung Frances , Mezei Gabor
Published: November 2003

Background

Iletrospective studies fail to identify predictors of postoperative nausea and vomiting (PONV). The authors prospectively studied 17,638 consecutive outpatients who had surgery to identify predictors.

Methods

Data on medical conditions, anesthesia, surgery, and PONV were collected in the post-anesthesia care unit, in the ambulatory surgical unit, and in telephone interviews conducted 24 h after surgery. Multiple logistic regression with backward stepwise elimination was used to develop a predictive model An independent set of patients was used to validate the model

Results

Age (younger or older), sex (female or male), smoking status (nonsmokers or smokers), previous PONV, type of anesthesia (general or other), duration of anesthesia (longer or shorter), and type of surgery (plastic, orthopedic shoulder, or other) were independent predictors of PONV. A 10-yr increase in age decreased the likelihood of PONV by 13%. The risk for men was one third that for women. A 30-min increase in the duration of anesthesia increased the likelihood of PONV by 59%. General anesthesia increased the likelihood of PONV 11 times compared with other types of anesthesia. Patients with plastic and orthopedic shoulder surgery had a sixfold increase in the risk for PONV. The model predicted PONV accurately and yielded an area under the receiver operating characteristic curve of 0.785+/-0.011 using an independent validation set.

Conclusions

A validated mathematical model is provided to calculate the risk of PONV in outpatients having surgery. Knowing the factors that predict PONV will help anesthesiologists determine which patients will need antiemetic therapy.
Sevoflurane Increases Lumbar Cerebrospinal Fluid Pressure in Normocapnic Patients Undergoing Transsphenoidal Hypophysectomy
Authors: Talke Pekka , Caldwell James E. , Richardson Charles A.
Published: November 2003

Background

The data on the effect of sevoflurane on intracranial pressure in humans are still limited and inconclusive. The authors hypothesized that sevoflurane would increase intracranial pressure as compared to propofoL METHODS: In 20 patients with no evidence of mass effect undergoing transsphenoidal hypophysectomy, anesthesia was induced with intravenous fentanyl and propofol and maintained with 70% nitrous oxide in oxygen and a continuous propofol infusion, 100 microg x kg(-1) x min(-1). The authors assigned patients to two groups randomized to receive only continued propofol infusion (n = 10) or sevoflurane (n = 10) for 20 min. During the 20-min study period, each patient in the sevoflurane group received, in random order, two concentrations (0.5 times the minimum alveolar concentration [MAC] and 1.0 MAC end-tidal) of sevoflurane for 10 min each. The authors continuously monitored lumbar cerebrospinal fluid (CSF) pressure, blood pressure, heart rate, and anesthetic concentrations.

Results

Lumbar CSF pressure increased by 2+/-2 mmHg (mean+/-SD) with both 0.5 MAC and 1 MAC of sevoflurane. Cerebral perfusion pressure decreased by 11+/-5 mmHg with 0.5 MAC and by 15+/-4 mmHg with 1.0 MAC of sevoflurane. Systolic blood pressure decreased with both concentrations of sevoflurane. To maintain blood pressure within predetermined limits (within+/-20% of baseline value), phenylephrine was administered to 5 of 10 patients in the sevoflurane group (range = 50-300 microg) and no patients in the propofol group. Lumbar CSF pressure, cerebral perfusion pressure, and systolic blood pressure did not change in the propofol group.

Conclusions

Sevoflurane, at 0.5 and 1.0 MAC, increases lumbar CSF pressure. The changes produced by 1.0 MAC sevoflurane did not differ from those observed in a previous study with 1.0 MAC isoflurane or desflurane.
Rapid Tracheal Intubation with Rocuronium
Authors: Kirkegaard-Nielsen Hans , Caldwell James E. , Berry Peter D.
Published: November 2003

Background

Rapid tracheal intubation with rocuronium has not been studied using a probability-based approach. The authors aimed to predict doses of rocuronium giving 90% and 95% probability of in intubation within 60 s and to estimate their durations of action.

Methods

After premedication with midazolam, 2 mg, anesthesia was induced in 80 subjects with fentanyl, 2 microg/kg, followed 3 min later by propofol, 2 mg/kg. Patients received randomly rocuronium, 0.0, 0.4, 0.8, or 1.2 mg/kg (n = 20/ dose). Laryngoscopy began 40 s later, aiming for intubation at 60 s, and conditions were graded perfect, acceptable, or unacceptable, with the first two conditions being successful intubation. Anesthesia was maintained with isoflurane 0.5-1.0% (end-tidal) and fentanyL Duration of action was time until reappearance of the first tactile train-of-four response. The dose versus fraction of patients with successful intubation was analyzed by logistic regression. Doses giving 90% and 95% (D90 and D95) probability of successful intubation were calculated.

Results

intubation was successful in 7, 11, 18, and 19 patients in the 0.0, 0.4, 0.8, and 1.2 mg/kg groups, respectively. The D90 and D95 doses (95% confidence limits in parentheses) were 0.83 (0.59-1.03) and 1.04 (0.76-1.36) mg/kg, respectively. Estimated time until first tactile train-of-four response after D90 and D95 doses was 32 and 46 min, respectively.

Conclusions

After induction with fentanyl and propofol, rocuronium, 1.04 mg/kg gives 95% probability of successful intubation at 60 s.