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Biomedical subjects

T A Bowdle

Publications and source records attributed to T A Bowdle.

At least 37 records · Page 2Linked to original sources
PubMed1991

Effect of serum protein binding on the entry of lidocaine into brain and cerebrospinal fluid in dogs.

To test the hypothesis that lidocaine passage into the central nervous system is a function of free rather than total lidocaine concentration, we examined the effect of serum protein binding on the distribution of lidocaine into brain and cerebrospinal fluid (CSF) in dogs. Six of the 13 dogs studied were pretreated with rifampin to induce a 4-fold increase (P = 0.019) in serum concentration of alpha 1-acid glycoprotein, which is a major binding protein for lidocaine. The dogs were anesthetized and prepared surgically to obtain samples of cortical brain tissue or CSF from the cisterna magna. Lidocaine at a dose of 3 mg/kg was infused intravenously over 15 s. Arterial blood and brain cortex or CSF were sampled serially during a 60-min interval and analyzed for lidocaine content. Unbound or free fraction of lidocaine in serum was measured by equilibrium dialysis. Rifampin pretreatment led to a significant decrease in average serum free fraction of lidocaine, from 0.24 +/- 0.08 to 0.080 +/- 0.030 (P less than 0.001). Total lidocaine concentration in serum was higher, but free lidocaine concentration was lower in the rifampin group. Equilibration of lidocaine between serum and brain or CSF was reached by 10 min after lidocaine administration. Rifampin-pretreated dogs had consistently lower partition ratios of lidocaine between brain and serum or between CSF and serum. A strong and positive correlation between time-averaged brain to serum or CSF to serum ratios and serum free fractions were observed (r = 0.92, P less than 0.001 for brain; r = 0.90, P less than 0.01 for CSF).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Hypokalemia before induction of anesthesia and prevention by beta 2 adrenoceptor antagonism.

We have observed that serum potassium levels measured immediately before induction of anesthesia ("preinduction K+") are often lower than those measured 1-3 days preoperatively ("preoperative K+"). The purpose of this investigation was to determine, in two studies, the magnitude of this difference and to elucidate the mechanism by which this occurs. In the first study, preinduction K+ (3.6 +/- 0.4 mEq/L, mean +/- SD) was significantly lower than K+ levels measured during routine preoperative testing (4.4 +/- 0.4 mEq/L, n = 47, P less than 0.001). Twenty-three patients (49%) had preinduction K+ levels that were considered hypokalemic (less than or equal to 3.5 mEq/L), but 22 of these 23 patients had normal preoperative K+ levels. The second study tested the hypothesis that preinduction decreases in serum K+ are mediated by beta 2-adrenergic receptors. Preinduction K+ changes were determined in patients given a single preoperative dose of propranolol (beta 1/beta 2-antagonist), atenolol (beta 1-antagonist), or no beta-blocker (control). The difference between preoperative and preinduction serum K+ in patients receiving propranolol (0.1 +/- 0.4 mEq/L) was significantly attenuated (P less than 0.02) compared with the difference in control subjects (0.5 +/- 0.4 mEq/L), but was not significantly different from controls in patients pretreated with atenolol (0.3 +/- 0.4 mEq/L). These results demonstrate that serum K+ levels measured intraoperatively just before anesthetic induction are consistently and significantly less than those measured 1-3 days preoperatively. The ability of propranolol but not atenolol to block this change suggests that the acute decrease in K+ levels was due to beta 2-adrenergic receptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Induction of anesthesia with small doses of sufentanil or fentanyl: dose versus EEG response, speed of onset, and thiopental requirement.

The purpose of this study was to examine the dose versus EEG response relationship, the speed of onset, and the thiopental requirement for induction of anesthesia with small doses of sufentanil and fentanyl. The power spectrum of the electroencephalogram (EEG) was used to quantify the effect of the opioids. Eight male surgical patients, 52-80 yr old, were randomly divided into eight groups of ten to receive fentanyl, 5, 7, 10, or 13 micrograms/kg, or sufentanil, 0.5, 0.7, 1.0, or 1.3 micrograms/kg. The opioid was given iv over 1 min at a constant rate of infusion. Three to four minutes after the start of the opioid dose, thiopental was given iv in 25 mg increments every 30 s until the patient was unconscious. Power in the 1-3 Hz band reached maximum levels in less than 4 min after the start of opioid administration. At fentanyl doses of 7.0 micrograms/kg or less, or sufentanil doses of 1.0 micrograms/kg or less, the EEG effects did not increase in proportion to the dose of opioid. There was not a significant difference in the maximum power achieved in the 1-3 Hz band for sufentanil, 0.5, 0.7 and 1.0, and fentanyl, 5 and 7 micrograms/kg. Doses of fentanyl, 10 or 13 micrograms/kg, or sufentanil, 1.3 micrograms/kg were substantially more effective; the maximum power increased significantly between 7 and 10 micrograms/kg of fentanyl and 1.0 and 1.3 micrograms/kg of sufentanil (P less than 0.0001). The potency of sufentanil and fentanyl were compared by super-imposing, the dose versus response (power) curves. The potency ratio was 1:8 (sufentanil:fentanyl).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Treatment of air embolism with a special pulmonary artery catheter introducer sheath in sitting dogs.

The treatment of venous air embolism by aspiration from central venous catheters is well established. However, some anesthesiologists prefer to use a pulmonary artery catheter to monitor patients undergoing a neurosurgical procedure in the sitting position. While offering certain advantages, pulmonary artery catheters may be of limited use in the treatment of venous air embolism because the small diameter of the proximal port is poorly suited for efficient air aspiration. The authors have designed a special pulmonary artery catheter introducer sheath which can be positioned by intravascular electrocardiography to provide an efficient and effective means of air aspiration, while permitting the simultaneous use of a pulmonary artery catheter for pressure monitoring. The flow characteristics of this sheath, with and without side holes, were tested in vitro by measuring the time required to aspirate 50 ml of blood. The introducer sheath was compared to a Sorenson CVP catheter, a Bunegin-Albin Air Aspiration CVP Catheter, and the proximal port of a pulmonary artery catheter. The rank order of flow rate was: Bunegin-Albin CVP greater than introducer sheath without side holes = introducer sheath with side holes greater than Sorenson CVP greater than pulmonary artery catheter (P = 0.0001). The introducer sheath was then compared to a pulmonary artery catheter for the treatment of a 4 ml/kg venous air embolism in sitting, anesthetized dogs. The mean proportion of air retrieved by the sheath with or without side holes, 57% and 80%, respectively, was significantly greater than that retrieved by simultaneous aspiration of atrial and distal ports of the pulmonary artery catheter, 16% (P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Clinical pharmacology of antagonists of narcotic-induced respiratory depression. A brief review.

A variety of drugs have been used to antagonize the respiratory depression caused by narcotics. Some of these drugs, such as nalorphine, naloxone, butorphanol, and nalbuphine, are opiates, which interact directly with opiate receptors. Others, such as physostigmine, doxapram, and aminophylline, probably act indirectly by stimulating neuronal pathways involved in the regulation of ventilation. None of these drugs is ideal, and all have adverse side effects. Cardiovascular instability and eradication of analgesia have been troublesome, especially with the use of naloxone. The newer mixed agonist-antagonist agents, butorphanol and nalbuphine, may have significant advantages compared with naloxone. The purpose of this review is to summarize the pharmacology of the common narcotic antagonists, with an emphasis on obtaining acceptable results while avoiding adverse side effects.

Animals↗
PubMed1987

Propranolol reduces bupivacaine clearance.

Propranolol reduces the clearance of lidocaine by both reducing hepatic blood flow and inhibiting lidocaine metabolism. The authors investigated the possibility that propranolol reduces the clearance of bupivacaine as well. Bupivacaine, 30-50 mg, was administered intravenously to six normal human volunteers, over 10-15 min on two occasions, at least 2 weeks apart. Propranolol, 40 mg orally every 6 h, was used on one occasion, beginning 24 h prior to the bupivacaine administration. The sequence of the sessions was randomized. Twenty-two venous blood samples were obtained over 36 h in order to determine bupivacaine clearance, terminal elimination rate constant, and volume of distribution. All subjects experienced mild CNS toxicity, consisting of tinnitus, facial tingling, or subtle visual disturbances, associated with peak venous plasma concentrations of 0.81 to 2.7 micrograms/ml. Mean bupivacaine clearance was 0.33 +/- 0.12 l/min for the control session and 0.21 +/- 0.12 l/min during propranolol use, a significant 35% reduction (P less than 0.01). The terminal elimination rate constant (beta) was 0.27 +/- 0.16 h-1 for the control session and 0.14 +/- 0.069 h-1 with propranolol (P less than 0.05); terminal elimination half-lives were 2.6 and 4.9 h, respectively. Volume of distribution was unchanged. Because bupivacaine clearance should be relatively insensitive to hepatic perfusion, it appeared that propranolol caused a substantial inhibition of bupivacaine metabolism at the level of the hepatocyte. These data suggest that concomitant use of propranolol could result in the accumulation of a toxic concentration of bupivacaine.

Adult↗
PubMed1987

Butorphanol improves CO2 response and ventilation after fentanyl anesthesia.

We have determined that the mixed agonist-antagonist narcotic, butorphanol, improves CO2 response and ventilation after fentanyl anesthesia. A tentative dosage range has been established. Twenty-two patients were anesthetized with isoflurane, nitrous oxide, and fentanyl, which was continuously infused throughout the study. Postoperatively three 1-mg doses of butorphanol were administered IV. Blood pressure, heart rate, plasma epinephrine and norepinephrine concentrations, and pain intensity were essentially unchanged after butorphanol. Most of the improvement in breathing occurred after the first 1-mg dose. Mean respiratory rate increased from 7.8 +/- 5.0 to 11.0 +/- 4.8 min-1 (P less than or equal to 0.005), tidal volume increased from 469 +/- 302 to 844 +/- 390 ml (P less than or equal to 0.005), minute ventilation increased from 4.32 +/- 2.97 to 8.51 +/- 3.14 L/min (P less than or equal to 0.005), and the slope of the ventilatory response to CO2 increased from 0.36 +/- 0.37 to 0.90 +/- 0.80 L X min-1 X mm Hg-1 (P less than or equal to 0.05). Resting PaCO2 decreased from a baseline of 57.8 +/- 11.1 to 51.7 +/- 5.12 mm Hg (P less than or equal to 0.05) after the third dose.

Anesthesia Recovery Period↗
PubMed1984

Caudal anesthesia with lidocaine or bupivacaine: plasma local anesthetic concentration and extent of sensory spread in old and young patients.

Continuous caudal peridural anesthesia with 2% lidocaine (6 mg/kg) or 0.75% bupivacaine (2.2 mg/kg), both with epinephrine 1:200,000, was studied in two groups of male patients, younger than 40 or older than 55 yr old, respectively. Patients receiving lidocaine in the younger group (n = 6) were 32 +/- 5.2 (mean +/- SD) yr old and weighed 75 +/- 12 kg, while those in the older group (n = 16) were 66 +/- 5.3 yr old and weighed 72 +/- 8.2 kg. Patients receiving bupivacaine in the respective groups were 27 +/- 7.0 yr old (n = 5), and 76 +/- 10 kg compared to 69 +/- 10 yr (n = 14) and 75 +/- 10 kg. Anesthesia was satisfactory in all patients. Extent of sensory anesthesia, peak plasma lidocaine or bupivacaine concentrations, and area under the plasma concentration-time curves were independent of age. No local anesthetic toxicity was observed and peak drug concentrations were below those commonly associated with toxicity.

Adult↗
PubMed1982

The influence of free fatty acids on valproic acid plasma protein binding during fasting in normal humans.

The effect of physiologic variations of free fatty acid levels on in vivo valproic acid plasma protein binding was studied in 6 healthy adult subjects. 14 blood samples were taken during a 12-h dosing interval at steady state while in a fed condition and also during a 27 h fast. Free fraction and total valproate concentration were determined by equilibrium dialysis and GLC, respectively. Free fatty acid levels were determined from both fresh samples and samples incubated at 37 degrees C for 12 h, the latter in order to simulate equilibrium dialysis conditions. Fasting resulted in increased serum free fatty acid levels in all subjects, ranging from 34-182% (p less than 0.01). Incubation also caused free fatty acid levels to rise, more so in fed samples (50-87%, p less than 0.01) than in fasting samples (10-50%, p less than 0.01). Fasting resulted in a 9% increase in the mean free fraction for all subjects combined (P less than 0.01). Regression analysis of 180 sets of values for free fraction, total valproate concentration and free fatty acid level suggested that valproate concentration accounts for 17% and free fatty acid level for 37% of the variation in free fraction. Mean clearance was unchanged by fasting despite an increased free fraction suggesting decreased intrinsic clearance (i.e. decreased metabolism) of valproate under these conditions.

Adult↗
PubMed1980

Phenytoin pharmacokinetics in burned rats and plasma protein binding of phenytoin in burned patients.

Unexpectedly low serum phenytoin levels occurred in burned epileptic patients, suggesting the possibility of altered phenytoin disposition. Subsequently, phenytoin log-linear elimination kinetics after a 10 mg/kg i.v. single dose was examined in a burned rat model. Clearance increased from 1.08 +/- 0.28 liters/hr/kg in control rats to 1.50 +/- 0.38 liters/hr/kg in burned rats (P less than .05). The volume of distribution increased from 0.82 +/- 0.058 liters/kg in control rats to 1.01 +/- 0.11 liters/kg in burned rats (P less than .0005). The first order elimination rate constant (KE) did not change significantly (1.31 +/- 0.37) hr-1 in control rats vs. 1.52 +/- 0.48 hr-1 in burned rats; P greater than .05). The increase in clearance and in volume of distribution could be explained on the basis of a decrease in plasma protein binding. The free fraction in plasma increased from 27.1% +/- 1.2 in controls to 33.4% +/- 1.6 in burned rats (P less than .0005). The change in binding was consistent with a decrease in serum albumin from 2.64 +/- 0.33 g/dl in controls to 1.98 +/- 0.16 g/dl in burned rats (P less than .0005). Plasma samples of four burned human subjects revealed low serum albumin and markedly decreased plasma protein binding of phenytoin (2- to 3-fold increase in free fraction in plasma).

Adult↗