Plasma concentrations of isoniazid in children with tuberculous infections.

Six children with tuberculous infection were given their daily prescribed doses of isoniazid by the oral and the intramuscular route on different days. The plasma concentrations reached after both routes of administration were nearly equivalent. The plasma half-life of isoniazid ranged from 1.6 to 4.8 hours. The observed plasma concentrations in these children were higher than those reported in many adults. This difference is due to the larger doses of isoniazid prescribed for children.

Hemodynamic response of calves to tiletamine-zolazepam-xylazine anesthesia.

Six healthy Holstein calves were anesthesized with isoflurane in O2 and instrumented for hemodynamic studies. A saphenous artery was catheterized for measurement of blood pressure and withdrawal of blood for determination of the partial pressure of carbon dioxide (PaCO2), oxygen (PaO2), and arterial pH (pHa). Respiration was controlled throughout the study. The ECG and EEG were monitored continuously. A thermodilution catheter was passed via the right jugular vein into the pulmonary artery for determination of cardiac output and measurement of central venous pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure. Baseline values (time 0) were recorded following recovery from isoflurane. Tiletamine-zolazepam (4 mg/kg)-xylazine (0.1 mg/kg) were administered IV immediately after recording baseline values. Values were again recorded at 5, 10, 20, 30, 40, 50, and 60 minutes after injection. Changes in left ventricular stroke work index, PaCO2, and pHa were insignificant. Arterial blood pressure and systemic vascular resistance increased above baseline at 5 minutes and then gradually decreased below baseline at 40 minutes, demonstrating a biphasic response. Values for pulmonary capillary wedge pressure, pulmonary arterial pressure, central venous pressure, and PaO2 were increased above baseline from 5 to 60 minutes. Stroke volume, stroke index, and right ventricular stroke work index were increased from 20 or 30 minutes to 60 minutes. Pulmonary vascular resistance increased at 10 minutes, returned to baseline at 20 minutes, and was increased again at 60 minutes. Heart rate, cardiac output, cardiac index, and rate pressure product were decreased at 5 minutes, and with the exception of cardiac output, remained so for 60 minutes. Cardiac output returned to the baseline value at 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in the arrhythmogenic dose of epinephrine after xylazine or medetomidine administration in halothane-anesthetized dogs.

Eight dogs (12.5 to 21.5 kg) were assigned at random to each of 3 groups that were not given glycopyrrolate (HS, HX, HM) and to each of 3 groups that were given glycopyrrolate (HGS, HGX, HGM). Dogs were anesthetized with halothane (1.31% end-tidal concentration), and ventilation was controlled (PCO2 35 to 40 mm of Hg end-tidal concentration). Glycopyrrolate was administered IV and IM at a dosage of 11 micrograms/kg of body weight, each. Saline solution, xylazine (1.1 mg/kg, IM), or medetomidine (15 micrograms/kg, IM) was administered 10 minutes after baseline arrhythmogenic dose of epinephrine (ADE) determination. Redetermination of the ADE at the same infusion rate was started 10 minutes after drug administration. Arrhythmogenic dose was determined by constant infusion of epinephrine at rates of 1.0 and 2.5 micrograms/kg/min. The ADE was defined as the total dose of epinephrine inducing at least 4 ectopic ventricular depolarizations within 15 seconds during a 3-minute infusion or within 1 minute after the end of the infusion. Total dose was calculated as the product of infusion rate and time to arrhythmia. Statistical analysis of the differences between baseline ADE and posttreatment ADE for groups HS, HX, and HM was performed by use of one-way ANOVA.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in the arrhythmogenic dose of epinephrine after xylazine or medetomidine administration in isoflurane-anesthetized dogs.

Eight dogs (body weight, 12.5 to 21.5 kg) were assigned at random to each of 3 treatment groups (IS, IX, IM) that were not given glycopyrrolate and to each of 3 groups that were given glycopyrrolate (IGS, IGX, IGM). Dogs were anesthetized with isoflurane (1.95% end-tidal concentration), and ventilation was controlled (PCO2, 35 to 40 mm of Hg end-tidal concentration). Glycopyrrolate was administered IV and IM at a dosage of 11 micrograms/kg of body weight, each. Saline solution, xylazine (1.1 mg/kg, IM), or medetomidine (15 micrograms/kg, IM) was administered 10 minutes after baseline ADE determination. Redetermination of the ADE at the same infusion rate was started 10 minutes after drug administration. Arrhythmogenic dose was determined by constant infusion of epinephrine at rates of 1.0, 2.5, and 5.0 micrograms/kg/min. The ADE was defined as the total dose of epinephrine that induced at least 4 ectopic ventricular depolarizations within 15 seconds during a 3-minute infusion, or within 1 minute after the end of the infusion. Total dose was calculated as the product of infusion rate and time to arrhythmia. Statistical analysis of the differences between baseline and treatment ADE values was performed by use of one-way ANOVA. Mean +/- SEM baseline ADE values for groups IS, IX, and IM were 1.55 +/- 0.23, 1.61 +/- 0.28, and 1.95 +/- 0.65 micrograms/kg, respectively. Differences for groups IS, IX, and IM were -0.12 +/- 0.05, -0.31 +/- 0.40, and -0.17 +/- 0.26, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic and analgesic effects of propofol infusion in medetomidine-premedicated dogs.

Hemodynamic and analgesic effects of medetomidine (30 micrograms/kg of body weight, IM), atropine (0.044 mg/kg, IM), and propofol (2 mg/kg, IV, as a bolus, and 165 micrograms/kg/min, IV, for 60 minutes, as an infusion) were evaluated in 6 healthy adult Beagles. Catheters were placed while the dogs were anesthetized with isoflurane in oxygen. Administration of isoflurane was then discontinued, and dogs were allowed to breath oxygen until end-tidal isoflurane concentration was < or = 0.5%. At this time, baseline measurements were recorded and medetomidine and atropine were administered. Ten minutes later, the bolus of propofol was given and the infusion was begun. Analgesia was evaluated with a tail clamp test and by use of a direct-current nerve stimulator. Sinoatrial and atrioventricular blockade developed in all 6 dogs within 2 minutes of administration of medetomidine and atropine, but disappeared within 10 minutes. Apnea did not develop after administration of propofol. Analgesia was strong and consistent throughout the entire 60-minute period of propofol infusion. Medetomidine significantly (P < 0.05) increased systemic vascular resistance and decreased cardiac output, compared with baseline values. Propofol infusion appeared to alleviate medetomidine-induced vasoconstriction. Recovery was smooth and uncomplicated. All dogs were able to walk normally at a mean time (+/- SEM) of 88.2 +/- 20.6 minutes after termination of propofol infusion. It was concluded that medetomidine, atropine, and propofol, as given in the present study, is a safe combination of anesthetic drugs for use in healthy Beagles.

Influence of anesthetic regimens on the perioperative catecholamine response associated with onychectomy in cats.

Plasma catecholamine concentrations in response to onychectomy were examined in 27 cats receiving different anesthetic regimens. Each cat was anesthetized with a dissociative-tranquilizer combination, and onychectomy was performed on 1 forefoot. One week later, each cat was anesthetized with the same dissociative-tranquilizer combination plus either butorphanol or oxymorphone, and onychectomy was performed on the other forefoot. Four treatment groups were studied: tiletamine-zolazepam and tiletamine-zolazepam-butorphanol combinations were administered to group-1 cats, ketamine-acepromazine and ketamine-acepromazine-butorphanol combinations were administered to group-2 cats, tiletamine-zolazepam and tiletamine-zolazepam-oxymorphone combinations were administered to group-3 cats, and ketamine-acepromazine and ketamine-acepromazine-oxymorphone combinations were administered to group-4 cats. All drug combinations were administered IM. Central venous blood samples were drawn for catecholamine analysis after injection of drug(s), after onychectomy, and 1, 2, and 4 hours after injection. Tiletamine-zolazepam alone or tiletamine-zolazepam-butorphanol prevented epinephrine release for 2 hours after injection of drug(s). Norepinephrine concentration increased significantly (P < 0.05) from baseline after onychectomy for tiletamine-zolazepam-butorphanol and at 4 hours for tiletamine-zolazepam and tiletamine-zolazepam-butorphanol. After onychectomy, there was no difference in epinephrine values between tiletamine-zolazepam and tiletamine-zolazepam-oxymorphone. Ketamine-acepromazine prevented increases in norepinephrine and epinephrine concentrations for up to 2 hours after surgery. Addition of butorphanol to ketamine-acepromazine decreased norepinephrine values immediately after onychectomy. Addition of oxymorphone to ketamine-acepromazine resulted in lower epinephrine values 4 hours after surgery.

Hemodynamic and anesthetic effects of etomidate infusion in medetomidine-premedicated dogs.

Hemodynamic and analgesic effects of medetomidine (15 micrograms/kg of body weight, IM) and etomidate (0.5 mg/kg, IV, loading dose; 50 micrograms/kg/min, constant infusion) were evaluated in 6 healthy adult Beagles. Instrumentation was performed during isoflurane/oxygen-maintained anesthesia. Before initiation of the study, isoflurane was allowed to reach end-tidal concentration < or = 0.5%, when baseline measurements were recorded. Medetomidine and atropine (0.044 mg/kg) were given IM after recording of baseline values. Ten minutes later, the loading dose of etomidate was given IM, and constant infusion was begun and continued for 60 minutes. Oxygen was administered via endotracheal tube throughout the study. Analgesia was evaluated by use of the standard tail clamp technique and a direct-current nerve stimulator. Sinoatrial and atrial-ventricular blocks occurred in 4 of 6 dogs within 2 minutes after administration of a medetomidine-atropine combination, but disappeared within 8 minutes. Apnea did not occur after administration of the etomidate loading dose. Analgesia was complete and consistent throughout 60 minutes of etomidate infusion. Medetomidine significantly (P < 0.05) increased systemic vascular resistance and decreased cardiac output. Etomidate infusion caused a decrease in respiratory function, but minimal changes in hemodynamic values. Time from termination of etomidate infusion to extubation, sternal recumbency, standing normally, and walking normally were 17.3 +/- 9.4, 43.8 +/- 14.2, 53.7 +/- 11.9, and 61.0 +/- 10.9 minutes, respectively. All recoveries were smooth and unremarkable. We concluded that this anesthetic drug combination, at the dosages used, is a safe technique in healthy Beagles.

Yohimbine/flumazenil antagonism of hemodynamic alterations induced by a combination of midazolam, xylazine, and butorphanol in dogs.

Reversal of hemodynamic alterations induced by midazolam maleate (1.0 mg/kg of body weight), xylazine hydrochloride (0.44 mg/kg), and butorphanol tartrate (0.1 mg/kg) with yohimbine (0.1 mg/kg) and flumazenil (0.25 mg/kg) was evaluated in 5 dogs. The dogs were anesthetized with isoflurane for instrumentation. With return to consciousness, baseline values were recorded, and the midazolam/xylazine/butorphanol mixture with glycopyrrolate was administered IV. Hemodynamic data were recorded for 60 minutes, and then a reversal mixture of yohimbine and flumazenil was administered IV. All variables were measured 1 minute from beginning of the reversal injection. Mean arterial pressure, pulmonary arterial pressure, systemic vascular resistance, and right ventricular stroke work index increased significantly (P < 0.05) above baseline at 60 minutes. Cardiac index and central venous pressure significantly decreased below baseline at 60 minutes. After reversal, mean arterial pressure and central venous pressure significantly decreased from baseline, whereas cardiac index, pulmonary arterial pressure, and right ventricular stroke work index increased significantly above baseline. Heart rate, cardiac index, and right ventricular stroke work index increased significantly above the 60-minute value after reversal. Mean arterial pressure and systemic vascular resistance decreased significantly (P < 0.05) below the 60-minute value after reversal. The hemodynamic alterations accompanying midazolam/xylazine/butorphanol sedation-anesthesia may be rapidly reversed with a combination of yohimbine and flumazenil.

Ability of flumazenil, butorphanol, and naloxone to reverse the anesthetic effects of oxymorphone-diazepam in dogs.

OBJECTIVE: To evaluate the ability of flumazenil (FLU), butorphanol (BUT), and naloxone (NAL) to reverse the anesthetic effects of oxymorphone-diazepam in dogs. ANIMALS: 6 healthy adult mixed-bread dogs. PROCEDURE: Dogs were randomly assigned to each of 6 reversal treatment groups. In each experiment, oxymorphone (0.22 mg/kg of body weight, i.v.) and diazepam (0.22 mg/kg. i.v.) were given sequentially 15 minutes after glycopyrrolate (0.01 mg/kg, i.v.) administration. Physiologic saline solution (SAL; 1 ml), FLU (0.01 mg/kg), BUT (0.44 mg/kg), or NAL (0.06 mg/kg) alone, or FLU-BUT or FLU-NAL (same dosages) was given i.v. as a reversal treatment 15 minutes after oxymorphone-diazepam administration. An individual unaware of the treatment protocol recorded time to extubation, sternal recumbency, and walking. RESULTS: Time to extubation was significantly (P < 0.05) less with BUT, NAL, FLU-BUT, or FLU-NAL treatment, compared with that for SAL treatment. Time to sternal recumbency was less with BUT, NAL, FLU-BUT, or FLU-NAL treatment, compared with that for SAL treatment. Time to walking was less with FLU-BUT or FLU-NAL treatment, compared with that for SAL treatment. CLINICAL IMPLICATIONS: Flumazenil, in combination with BUT or NAL, can be used to reverse the anesthetic effects of oxymorphone-diazepam in dogs.

Ketamine, Telazol, xylazine and detomidine. A comparative anesthetic drug combinations study in ponies.

This study was designed to assess the effects of 5 anesthetic drug combinations in ponies: (1) ketamine 2.75 mg/kg, xylazine 1.0 mg/kg (KX), (2) Telazol 1.65 mg/kg, xylazine 1.0 mg/kg (TX), (3) Telazol 2 mg/kg, detomidine 20 micrograms/kg (TD-20), (4) Telazol 2 mg/kg, detomidine 40 micrograms/kg (TD-40), (5) Telazol 3 mg/kg, detomidine 60 micrograms/kg (TD-60). All drugs were given iv with xylazine or detomidine preceding ketamine or Telazol by 5 min. Heart rate was decreased significantly from 5 min to arousal after TD-20 but only at 60 and 90 min after TD-40 and TD-60 respectively. Respiratory rate was decreased significantly for all ponies. Induction time did not differ between treatments. Duration of analgesia was 10 min for KX, 22.2 min for TX, 27.5 min for TD-20, 32.5 min for TD-40, and 70 min for TD-60. Arousal time was significantly longer with detomidine and Telazol. Smoothness of recovery was judged best in ponies receiving KX and TD-40. All ponies stood unassisted 30 min after signs of arousal.

Management by consent in human-machine systems: when and why it breaks down.

This study examined the effects of conflict type, time pressure, and display design on operators' ability to make informed decisions about proposed machine goals and actions in a management-by-consent context. A group of 30 B757 pilots were asked to fly eight descent scenarios while responding to a series of air traffic control clearances. Each scenario presented pilots with a different conflict that arose from either incompatible goals contained in the clearance or inappropriate implementation of the clearance by automated flight deck systems. Pilots were often unable to detect these conflicts, especially under time pressure, and thus failed to disallow or intervene with proposed machine actions. Detection performance was particularly poor for conflicts related to clearance implementation. These conflicts were most likely to be missed when automated systems did more than the pilot expected of them. Performance and verbal protocol data indicate that the observed difficulties can be explained by a combination of poor system feedback and pilots' difficulties with generating expectations of future system behavior. Our results are discussed in terms of their implications for the choice and implementation of automation management strategies in general and, more specifically, with respect to risks involved in envisioned forms of digital air-ground communication in the future aviation system. Actual or potential applications of this research include the design of future data link systems and procedures, as well as the design of future automated systems in any domain that rely on operator consent as a mechanism for human-machine coordination.

Pharmacokinetics of 3H-fentanyl in the dog anesthetized with enflurane.

Fentanyl is often used as an anesthetic supplement for short procedures because it has a rapid onset and brief duration of action. However, persistence of ventilatory depression several hours following the last dose has been seen. The authors studied the pharmacokinetics of fentanyl in the dog to find an explanation for the occasionally prolonged duration of action. 3H-fentanyl citrate, 10 or 100 microgram/kg, was injected intravenously in dogs anesthetized with enflurane-O2. Arterial plasma and urine were analyzed for unchanged 3H-fentanyl and for total 3H radioactivity. Kinetic indices were derived by nonlinear least-squares analysis of log concentration (ng/ml) vs. time relationships. Initially, the elimination of fentanyl from plasma was very rapid, and 98 per cent of the amount administered was removed from plasma in the first 5 min after an intravenous injection. However, the terminal elimination phase was prolonged (t1/2 = 199 +/- 17 min). The apparent volume of distribution was large (9.81/kg) and independent of dose. Repetitive doses produced an accumulation of fentanyl. 3H-labelled metabolites of fentanyl were present in the earliest samples of plasma, and accounted for the major portion of the total 3H radioactivity in both plasma and urine. Urine collected for six hours contained 36 per cent of the total 3H radioactivity administered, but only 4 per cent of fentanyl administered was excreted as unchanged fentanyl. The authors conclude that most of a single dose of fentanyl is rapidly eliminated from the body by biotransformation and leads to accumulation of the drug when administered in very large or repeated doses. Under these circumstances the slow release of drug from tissues results in persistent plasma levels of fentanyl and a prolonged duration of action.

Elimination kinetics of isoniazid in the newborn infant.

The elimination of isoniazid was followed in 2 newborn infants who had received the drug transplacentally, and in 1 of the mothers. The half-time for serum elimination for mother No. 1, babies No. 1 and 2 were calculated as 3.0, 7.8 and 19.8 h, respectively. Near equality existed between maternal and newborn serum isoniazid concentrations. Additional studies are required to determine the acetylation capacity of newborns.

Electromyography of the reticulum, abomasum and duodenum in dairy cows with left displacement of the abomasum.

Electromyographic (EMG) recordings of the reticulum, abomasal corpus, pyloric antrum and duodenum of six dairy cows with left displacement of the abomasum (LDA) were made in order to substantiate abomasal atony as a prerequisite to abomasal displacement. EMG recordings were made when LDA was present as well as when absent. Mean values were determined in five of six cows for the maximum peak or amplitude, mean peak values, peak-to-peak interval and count of the electrical response activity (ERA) for each 15 min segment of the waveform recordings. Segments containing phase III migrating myoelectric activity were not analysed. LDA positive periods were compared to LDA negative periods in each cow. The 6 h period (transition period) prior to the diagnosis of LDA was analysed separately. Paired t-tests were applied to group values with statistical significance established at the P = 0.05 level. There was a significant decrease in the ERA count during the LDA positive periods in the abomasal corpus (-1.40% to -7.88%, P = 0.0217) and in the pyloric antrum (-2.05% to -11.98%, P = 0.0430). A corresponding significant increase occurred in the peak-to-peak interval. During the transition period spike activity in the duodenum increased 0.5% to 48.31% (P = 0.0474) and the peak-to-peak interval was significantly decreased. No extended periods of atony were observed in the abomasum during this study.

Spectrophotofluorometric assay for isoniazid and acetyl isoniazid in plasma adapted to pediatric studies.

We modified the micro-scale spectrophotofluorometric method of Miceli et al. [Biochem. Med. 12, 348 (1975)] for the assay of "apparent" isoniazid (isoniazid acid-lable hydrazones) to improve its clinical application. We also adapted the method for determination of acetyl isoniazid. Data are presented showing how long plasma containing isoniazid may validly be stored. The applicability of the method was demonstrated in studies on children and small animals.

Hemodynamic effects of intravenous midazolam-xylazine-butorphanol in dogs.

The hemodynamic effects of a mixture of midazolam (1.0 mg/kg), xylazine (0.44 mg/kg), and butorphanol (0.1 mg/kg) were evaluated in six adult dogs. The dogs were anesthetized with isoflurane for instrumentation. As the dogs returned to consciousness, baseline values were recorded and the midazolam-xylazine-butorphanol mixture and glycopyrrolate (0.01 mg/kg) were administered intravenously (IV). Hemodynamic data were recorded 3, 10, 20, 30, 40, 50, and 60 minutes after injection. Mean arterial pressure (AP), mean pulmonary arterial pressure (PAP), heart rate (HR), rate-pressure product (RPP), mean pulmonary capillary wedge pressure (PCWP), systemic vascular resistance (SVR), and right ventricular stroke work index (RVSWI) were increased significantly above baseline values. Cardiac output (CO), stroke volume (SV), cardiac index (CI), stroke index (SI), mean central venous pressure (CVP), and left ventricular stroke work index (LVSWI) were decreased significantly below baseline values. When administered IV at the dosages used in this study, midazolam-xylazine-butorphanol-glycopyrrolate induced profound acute alterations in several critical hemodynamic variables.

A comparison of medetomidine-propofol and medetomidine-midazolam-propofol anesthesia in rabbits.

We evaluated and compared the effects of medetomidine-propofol and medetomidine-midazolam-propofol anesthesia in rabbits. Fourteen New Zealand White rabbits were randomly assigned to receive either medetomidine (0.25 mg/kg, i.m.)-atropine (0.5 mg/kg, i.m.)-propofol (4 mg/kg, i.v.) (n = 7) or medetomidine (0.25 mg/kg, i.m.)-atropine (0.5 mg/kg, i.m.)-midazolam (0.5 mg/kg, i.m.)-propofol (2 mg/kg, i.v.) (n = 7). Five minutes after medetomidine-atropine or medetomidine-atropine-midazolam i.m. injection, propofol was administered i.v. Both medetomidine and medetomidine-midazolam rapidly (within 5 minutes) immobilized all rabbits and greatly eased the i.v. administration of propofol. Endotracheal intubation was accomplished easily after propofol injection in both groups. There was no significant difference between medetomidine-propofol and medetomidine-midazolam-propofol-treated rabbits in heart rate, respiratory rate, mean arterial pressure, or end-tidal CO2. The addition of midazolam to the medetomidine-propofol regimen significantly (P < 0.05) prolonged the duration of ear-pinch analgesia (25.0 +/- 7.1 vs. 36.7 +/- 8.9 minutes), the time from extubation to sternal recumbency (0.0 vs. 26.7 +/- 8.1 minutes), and the time from extubation to standing (0.0 vs. 39.5 +/- 11.3 minutes) without inducing significant changes in arterial blood pressure and end-tidal alveolar CO2. We consider both medetomidine-propofol and medetomidine-midazolam-propofol combinations to be safe and effective regimens for induction and short-term anesthesia in rabbits.

The hemodynamic response of calves to tiletamine-zolazepam anesthesia.

Six isoflurane-anesthetized calves were instrumented for hemodynamic studies and allowed to recover from anesthesia. When the mean arterial blood pressure rose to 100 mmHg or when vigorous movement occurred, a 1:1 tiletamine-zolazepam mixture (4 mg/kg) was administered intravenously (IV). Values for cardiac output, cardiac index, stroke index, central venous pressure, and right ventricular stroke work index did not change significantly. Systolic, mean, and diastolic arterial blood pressures and systemic vascular resistance were significantly decreased below baseline at 5 minutes; they were significantly increased above baseline at 20 minutes and remained so throughout the 60 minute study. Changes in left ventricular stroke work index and rate pressure product were similar to those of arterial blood pressure and systemic vascular resistance, although they were not significant. Heart rate and pulmonary capillary wedge pressure decreased significantly but gradually returned to baseline at 40 minutes and then increased significantly above baseline by the end of the study. Minor venous-arterial shunting or perhaps mismatching of ventilation and perfusion appeared to have developed in the later stages of the study. This was reflected in a minor increase in the arterial partial pressure of carbon dioxide (PaCO2) and a decrease in the arterial partial pressure of oxygen (PaO2) and arterial pH. At the dose administered, the hemodynamic changes induced by tiletamine-zolazepam were minimal and were compatible with safe anesthesia in calves.