Ming-Hwang Shyr

Concentration and regional distribution of propofol in brain and spinal cord during propofol anesthesia in the rat

We evaluated the pharmacokinetics and regional distribution of propofol in the brain and spinal cord during propofol anesthesia in Sprague-Dawley rats, using high-performance liquid chromatographic determination of propofol concentration in brain, whole blood and plasma. We found that the concentration of propofol in the brain increased and decreased expeditiously during and after a 15-min and 30-min period of i.v. infusion of an anesthetic dose (60 mg/kg per h) of propofol. Furthermore, propofol was evenly distributed in the brain and spinal cord during infusion, with a significant inter-individual variation. Upon the establishment of anesthesia 15 and 30 min following intravenous infusion of propofol, the concentration of propofol in the brain, whole blood and plasma was respectively 15.7 +/- 1.9 and 39.4 +/- 2.7 micrograms/g, 4.5 +/- 1.2 and 13.6 +/- 1.3 micrograms/ml and 1.8 +/- 0.5 and 5.1 +/- 0.9 micrograms/ml (mean +/- SEM, n = 6 or 7). These high brain/blood and brain/plasma ratios during anesthesia suggest that propofol manifests a pharmacokinetic profile that is different from at least thiopental.

Video-assisted mitral valve operations

BACKGROUND Video-assisted endoscopy has been applied frequently in the management of a variety of surgical diseases. However, it has rarely been applied in mitral valve surgery. METHODS We report 2 patients who received emergency operations for thrombosis of a mitral prosthesis (patient 1, a 68-year-old man) and acute mitral regurgitation due to rupture of anterior chordae (patient 2, a 75-year-old woman). They both had severe congestive heart failure. Cardiogenic shock was noted in patient 2. The mitral valve was approached through a right anterior minithoracotomy with the aid of an endoscope by means of projected images on the video monitor under femorofemoral cardiopulmonary bypass. The aorta was not cross-clamped, and the myocardium was protected by continuous coronary perfusion with hypothermic fibrillatory arrest. The left atrium was entered posterior to the interatrial groove. Thrombectomy and mitral valve repair were performed successfully. RESULTS The duration of extracorporeal circulation was 204 and 147 minutes, respectively. Both patients recovered from the operation rapidly with uneventful postoperative courses. CONCLUSIONS Our preliminary results suggest that video-assisted endoscopic cardiac surgery is technically feasible and could be performed in the milieu of open heart surgery.

A dose ranging study of dexamethasone for preventing patient-controlled analgesia-related nausea and vomiting: A comparison of droperidol with saline

We designed this study to determine the minimum dose of dexamethasone for preventing nausea and vomiting associated with the use of morphine by patient-controlled analgesia (PCA). Two hundred forty female patients were randomly assigned to receive dexamethasone 2, 4, 8, or 12 mg IV immediately before induction of anesthesia. Droperidol (0.1 mg/mL with morphine 1 mg/mL in PCA pump) and saline were used as controls. The complete response (no postoperative nausea and vomiting and no need for rescue antiemetic for a 24-h postoperative period) rates for dexamethasone 8 mg (72.2%) and 12 mg (78.9%) were significantly more than for saline (42.9%) (P < 0.05). Patients who received dexamethasone 12 or 8 mg also reported higher patient satisfaction than those who received saline (P < 0.05). These results were as effective as adding droperidol 0.1 mg/mL to the morphine PCA without causing drowsiness, restlessness, or arrhythmias. Smaller doses of dexamethasone (4 or 2 mg) were not effective for this propose. The results suggest that dexamethasone 8 mg IV is the minimum effective dose for the reduction of PCA morphine-related nausea and vomiting.

The intubating LMA: a comparison of insertion techniques with conventional tracheal tubes

Purpose: To compare the performance of the intubating laryngeal mask airway (ILMA) in assisting blind tracheal intubation with conventional tracheal tubes of different curvatures and the frequency of possible associated complications.Methods: After informed consent, 240 ASA I–II adults undergoing elective surgery participated in a randomized, single blind clinical trial to receive blind trachea intubation via ILMA with a conventional tracheal tube curved with normal (Normal group) or reversed (Reverse group) direction. More than three attempts at intubation was regarded as failure. The lowest oxygen saturation during intubation was recorded and postintubation sore throat and hoarseness were evaluated with verbal analog scales.Results: The overall success rates of intubation with Normal and Reverse groups were not different (96.7% and 94.2% respectively). Successful intubation at the first attempt was higher in the Reverse group than in the Normal group (86.7% vs 75.0%,P=0.033). The incidence of sore throat was higher in the Normal group than in the Reverse group (19.2% vs 9.2% respectively,P=0.042).Conclusions: Blind trachea intubation via an ILMA with the conventional curved tracheal tube is feasible and highly successful. Reverse curve direction is preferable at the first attempt of intubation for its higher success rate and lower incidence of complications.RésuméObjectif: Comparer le fonctionnement du masque laryngé d’intubation (MLI) utilisé avec des tubes endotrachéaux de différentes courbures, pour faciliter l’intubation endotrachéale à l’aveugle, et la fréquence de complications possibles.Méthode: Ayant donné leur consentement éclairé, 240 adultes d’état physique ASA I–II devant subir une intervention planifiée ont participé à un essai clinique randomisé et à l’insu. L’intubation, à l’aveugle avec le MLI et un tube endotrachéal de courbure habituelle (groupe normal) ou par insertion inversée (groupe inversé), était notée comme un échec si elle exigeait plus de trois essais. On a enregistré la plus faible saturation en oxygène pendant l’intubation et évalué, selon une échelle verbale analogique, le mal de gorge et la raucité de la voix qui ont pu suivre l’intubation.Résultats: Le taux de succès de l’intubation n’a pas présenté de différence intergroupe significative (96,7 % et 94,2 % respectivement). Une intubation réussie au premier essai a été plus fréquente dans le groupe inversé que dans le groupe normal (86,7 % vs 75,0 %,P=0,033). L’incidence de mal de gorge a été plus élevée dans le groupe normal que dans le groupe inversé (19,2 % vs 9,2 % respectivement,P=0,042).Conclusion: L’intubation endotrachéale à l’aveugle avec un MLI et un tube endotrachéal de courbure habituelle est possible et fréquemment réussie. L’insertion par inversion de la courbure, préférable au premier essai d’intubation, présente un meilleur taux de réussite et moins de complications.

Propofol anesthesia increases dopamine and serotonin activities at the somatosensory cortex in rats: a microdialysis study.

We sought to estimate the activities of dopamine and serotonin in animals receiving propofol anesthesia.The in vivo microdialysis technique was used in Sprague-Dawley rats (n = 6) to measure the major metabolites of dopamine and serotonin, i.e. 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (4-hydroxy-3-methyphenylacetic acid; HVA) and 5-hydroxy indole acetic acid (5-HIAA) in the somatosensory cortex. We also measured the levels of propofol in the brain and blood by microdialysis sampling in another group of rats (n = 6). During the experiment, the rat was infused intravenously (IV) with propofol at a rate of 10 mg [centered dot] kg-1 [centered dot] h-1 for 60 min and 60 mg [centered dot] kg-1 [centered dot] h-1 for 40 min. We found that IV infusion of propofol at a rate of 60 mg [centered dot] kg-1 [centered dot] h-1 significantly increased DOPAC, HVA, and 5-HIAA. We also determined that these changes correlated well with propofol levels in the brain and blood. We concluded that anesthetic doses of propofol increased the functional activities of dopamine and serotonin in the cortex. These increases correlate well with propofol levels in the cortex and blood. (Anesth Analg 1997;84:1344-8)

Prostacyclin analogue (OP-2507) induces delayed ex vivo neutrophil apoptosis and attenuates reperfusion-induced hepatic microcirculatory derangement in rats.

Leukocyte-endothelial adherence and changes of blood flow in microcirculation are associated with the development of ischemia-reperfusion injury in the liver. Polymorphonuclear neutrophil (PMN) apoptosis is essential to maintain homeostasis and plays a major role in limiting the reperfusion-related systemic effects. This study investigates the effects of a prostacyclin analogue (OP-2507) on hepatic ischemia-reperfusion injury. Adult, male Sprague-Dawley rats were used. Five groups were evaluated: (1) sham-operated control, n = 8; (2) ischemia control (1-h ischemia, 5-h reperfusion), n = 8; (3) intravenous infusion with OP-2507 ([15 cis-14-propylcyclohexyl]-16,17,18,19,20-pentanor-9-deoxy-9alpha,6-ni-trilo-PGF, methyl eater) at a dose of 1 microg/kg/min plus ischemia, n = 8; (4) intravenous infusion with OP-2507 at a dose of 0.1 microg/kg/min plus ischemia, n = 8, and (5) sham-operated control and intravenous infusion with OP-2507 at a dose of 1 microg/kg/min, N =8. Laser-Doppler flowmetry and an in vivo microscopy were used to investigate hepatic microcirculation. PMN apoptosis was quantitated by flow-cytometric labeling of DNA strand breaks. Tissue malondialdehyde and adenosine triphosphate were determined at the end of the experiment. Compared with the ischemia control group, OP-2507 significantly improved harmful insults following ischemia-reperfusion. The changes of mean systemic arterial pressure following ischemia-reperfusion have been significantly attenuated by OP- 2507 at both doses. OP-2507 lessened adherent leukocyte count in the post-sinusoid venules, and improved flow velocity in these areas. OP-2507 at both doses reduced malondialdehyde and increased adenosine triphosphate levels and this effect was dose-related. The activity of delayed ex vivo PMN apoptosis was significantly lower in the ischemia group than that of control and treatment groups. OP-2507 induced the activity of PMN apoptosis and its effect is dose-related, also. The PMN apoptosis activity is strongly correlated with parenchymal damages. This study demonstrates that OP-2507 treatment with ischemia may ameliorate the ischemia-reperfusion injury of the liver in the rat model, and increase spontaneous neutrophil apoptosis ex vivo.

Simultaneous determination of unbound ropivacaine in rat blood and brain using microdialysis

To investigate the pharmacokinetics of ropivacaine in rat blood and brain, a sensitive HPLC method and microdialysis were developed for the simultaneous determination of unbound ropivacaine in rat blood and brain. Adult, male Sprague-Dawley rats (290-350 g) were anesthetized with sodium pentobarbital (50 mg/kg, i.p.). Two microdialysis probes were inserted, one into the jugular vein toward right atrium, and one into the brain striatum of rats. Ropivacaine (5 mg/kg, i.v.) was then administered via the femoral vein. Blood and brain dialysates were collected and eluted with a mobile phase containing methanol-acetonitrite-20 mM monosodium phosphoric acid (pH 5.5) (10:40:50, v/v/v) in a liquid chromatographic system. Separation of ropivacaine was achieved by a CN column (Phenomenex Luna, 250x4.6 mm, particle size 5 microm; Torrance, CA, USA) within 10 min. The UV detector wavelength was set at 205 nm and the detection limit of ropivacaine was 20 ng/ml. The intra- and inter-day accuracy and precision of the analyses were less than 10% in the ranges of 0.02-5 microg/ml. The pharmacokinetic data were calculated from the individual animal measurements of dialysate concentration versus time. This method exhibits no endogenous interference and its sensitivity is sufficient for the determination of biological samples. The present results confirm that microdialysis sampling followed by LC separation with UV detection represents a viable approach for the measurement of free ropivacaine in rat brain and plasma.

Spinal nitric oxide participates in the control of the blood pressure during graded hemorrhage in the conscious rat

We sought to evaluate the role of spinal nitric oxide (NO) in the control of blood pressure in the conscious animal and determine its possible participation in the progression of hemorrhagic shock. Adult, male Sprague-Dawley rats were chronically prepared with intrathecal, intravenous, and intra-arterial catheters. We first investigated the role of spinal NO on blood pressure control by intrathecal administration of N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) at 0.37 micromol, 0.74 micromol. or 1.48 micromol. A dose-related increase in blood pressure was observed. We next pretreated animals with intrathecal or intravenous L-NAME at 0.37 micromol and induced the animal to shock by graded hemorrhage. Animals that received vehicle control or intravenous L-NAME had a decrease in blood pressure after 12% of the total circulatory blood volume (TBV) had been removed and developed severe hypotension after 24% TBV was bled. On the other hand, intrathecal pretreatment of L-NAME significantly attenuated the decrease in blood pressure. The blood pressure was maintained until 40% TBV had been withdrawn. We concluded that inhibition of NO synthase, in the spinal cord, increased blood pressure in a dose-dependent manner, and hemorrhagic shock induced by graded hemorrhage may involve an upregulation mechanism of spinal NO synthase in producing severe hypotension in conscious rats.

Power spectral analysis of arterial and central venous pressure signals during graded hemorrhage in anesthetized rats

Based on simultaneous power spectral analysis of systemic arterial pressure (SAP) and central venous pressure (CVP) signals in rats anesthetized with pentobarbital sodium, we assessed the hypotheses that subtle changes in the SAP spectrum exist during hemorrhagic shock, and that the CVP spectrum is a feasible index for central blood volume during acute graded blood loss. During Stage I hemorrhagic shock seen after reduction in 10% of total blood volume (TBV), there was a significant increase in the power of both the very low frequency (VLF, 0-.25 Hz) and low frequency (LF, .25-.8 Hz) components, along with a moderate decrease in the very high frequency (VHF, 5-9 Hz) component, of SAP signals. Substantial reduction in VLF, LF, and VHF components in the SAP spectrum occurred after a blood loss of 25% of TBV (Stage II), which persisted during Stage III hemorrhagic shock when the withdrawn blood reached 50% of TBV and the mean SAP maintained at 40 mm Hg. The depressed SAP-VLF and SAP-LF components sustained the period of spontaneous recovery and subsequent retransfusion of shed blood, although the power of SAP-VHF component gradually elevated during these two periods. The power of the high-frequency (HF, .8-2.4 Hz) component of SAP signals increased discernibly only during Stage III, became significant on spontaneous recovery, and declined during retransfusion. Although CVP and CVP-VHF component progressively declined, the power of the CVP-HF component manifested a gradual increase that was significantly and reversely correlated with the reduction in TBV. We conclude that differential changes in individual components of the SAP spectrum occur during hemorrhagic shock, and that the CVP-HF component may be a reliable indicator for central blood volume during acute graded blood loss.

Severe Accidental Hypothermia, Diagnostic Confirmation Without a Low Reading Thermometer: A Case Report

We present a patient who, griefstruck at his mothers death,　 first tried to drown his sorrows in alcohol and then smashed his head into his mothers tombstone injuring his neck and rendering him quadriplegic. Unable to move, he spent a cold January night outside in the rain. On arrival at the Emergency Department (ED), he had a decreased level of consciousness and profound bradycardia. While hypothermia was suspected, the severity was not appreciated due to lack of a low reading thermometer. Through a careful review of the clinical and laboratory findings, we describe a process for extrapolating the core temperature and discuss the potential risks and front line needs for hypothermia patients in Taiwan.