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Biomedical subjects

R R Bartkowski

Publications and source records attributed to R R Bartkowski.

At least 19 recordsLinked to original sources
PubMed2001

Rapacuronium: first experience in clinical practice.

Rapacuronium is a new non-depolarizing relaxant with a fast onset and rapid recovery. It was approved for the market in the United States in August 1999. The reasons for its acceptance in practice and the niche it fills are the subject of this review. Rapacuronium has been accepted wherever rapid onset and short duration of action are advantageous. It has received the greatest acceptance in brief outpatient procedures that require tracheal intubation. The average time of recovery to a train-of-four ratio of 80% is about 25 min after a usual intubating dose of 1.5 mg kg-1, when block is reversed. Its rapid onset has led some to use it in rapid-sequence induction, but the exact place in this scenario is still being defined. Its spontaneous recovery is rapid enough that many practitioners do not reverse the block if the procedure is long enough. Data suggest that this is reasonable after 60 min and may even be earlier, even 30 min, if verified by monitoring. The main adverse effects of rapacuronium are bronchospasm, hypotension and tachycardia. Of these, only bronchospasm has had significant clinical impact. These effects are dose related and the recommended dose of 1.5 mg kg-1 may keep problems to a minimum. Because rapacuronium is a new drug with unique properties its use gradually increased in its first year. Because of the problems associated with succinylcholine, rapacuronium may have advantages for brief outpatient procedures and in cases where rapid termination of block is desired, provided its adverse effects can be minimized.

Ambulatory Surgical Procedures↗
PubMed1999

Recent advances in neuromuscular blocking agents.

Factors driving the development of neuromuscular blocking agents are discussed. The goal of recent development of neuromuscular blocking agents is to develop agents with fewer adverse effects than succinylcholine and greater control. Greater control can be achieved through a short duration of action and a fast onset, similar to that found with succinylcholine. Duration control can be achieved through rapid, reliable metabolism that is organ independent, as with cisatracurium, or that occurs in the liver, because this will fail only in patients with severe hepatic disease. Rapid onset can be achieved by giving higher doses of drugs that have a fast, reliable metabolism or a rapid distribution to tissue. This has been done with succinylcholine, cisatracurium, and mivacurium. It has been shown that a low-potency drug has a faster onset than a higher-potency drug, even at the same relative dose. Rocuronium was the first neuromuscular blocking agent marketed that was developed specifically as a low-potency drug for achieving a rapid onset. In a comparison with two other intermediate-duration neuromuscular blocking agents at equipotent doses, rocuronium's onset was about one minute, which was two minutes faster than that of either vecuronium or atracurium. Rapacuronium is an investigational intermediate-duration agent and is even less potent than rocuronium. Clinical studies have shown it to have a very rapid onset (about 50 seconds) and a short duration of action (15-25 minutes, depending on the dose). Its short duration of action will make it potentially useful for short surgical procedures and procedures in which nerve integrity must be monitored. At the same time, its onset time approaches that of succinylcholine. Recent advances have made the administration of neuromuscular blocking agents much easier because the newer nondepolarizing relaxants offer faster onset and greater control.

Animals↗
PubMed1995

Intraoperative hemodynamic, renin, and catecholamine responses after prophylactic and intraoperative administration of intravenous enalaprilat.

This study was designed to evaluate effects of enalaprilat, an angiotensin-converting enzyme inhibitor, on hemodynamic and hormonal responses during surgery at endotracheal intubation, incision, and limb-tourniquet inflation. Thirty patients undergoing limb procedures with general anesthesia (N2O/narcotic technique) and a pneumatic tourniquet were randomized to receive either preoperative enalaprilat (1.25 mg intravenously [i.v.] 20 min prior to induction) or intraoperative enalaprilat (0.625 mg i.v. at the onset of tourniquet-associated hypertension), with appropriate placebo controls. Arterial blood pressure and heart rate increased significantly in response to intubation in the placebo group. Although there were no significant differences in catecholamine levels, plasma renin activity was significantly increased at postincision in the preoperative-enalaprilat group versus the placebo group. This suggests that activation of the renin-angiotensin system may play a key role in mediation of intraoperative hemodynamic responses to endotracheal intubation. With respect to tourniquet hypertension, preoperative or intraoperative treatment with enalaprilat reduced neither the pressor response to tourniquet inflation nor the amount of enflurane subsequently required to control arterial blood pressure. These findings suggest that this response is mediated by pain pathways, and may be treated more effectively with anesthesia/analgesia.

Adolescent↗
PubMed1993

The pharmacokinetics of droperidol in anesthetized children.

Despite the wide use of droperidol to reduce nausea and vomiting in children, its pharmacokinetics have not been described in pediatric patients. Twelve ASA Class I-II children, undergoing tonsillectomy and adenoidectomy, received standardized anesthesia; none of the children received premedication. After induction of general anesthesia, droperidol (0.05 mg/kg) was injected intravenously as a bolus. Droperidol plasma concentrations were determined by radioimmunoassay. Pharmacokinetic data were analyzed by model-independent methods. The pharmacokinetic parameters (mean +/- SD) for the studied population were elimination half-life: 101.5 +/- 26.4 min, mean residence time: 127.2 +/- 28.6 min, volume of distribution at steady state: 0.58 +/- 0.29 L/kg and clearance: 4.66 +/- 2.28 mL.kg-1 x min-1. The clearance and volume of distribution at steady state values are lower than those reported for the adult population, and they apparently decreased in a parallel fashion. The smaller volume of distribution at steady state is consistent with the lipophilic distribution of droperidol and the reduced content of adipose tissue in children. The elimination half-time and mean residence time values are similar to those reported previously for adults. The relatively short half-life of droperidol for our pediatric population does not explain its extended antiemetic action. It does, however, reaffirm that the pharmacokinetic duration of a drug's action is only one of the determinants of its clinical duration.

Anesthesia, Inhalation↗
PubMed1993

Rocuronium onset of action: a comparison with atracurium and vecuronium.

The onset, maximal neuromuscular block, and duration of rocuronium were compared with atracurium and vecuronium during enflurane anesthesia. Sixty patients received rocuronium (80, 100, 120, or 160 micrograms/kg). Enflurane enhanced a rocuronium neuromuscular block in a dose-related manner; the ED50 was 104 +/- 11 and 83 +/- 7 micrograms/kg (SEM) during 1% and 2% enflurane anesthesia, respectively. Patients receiving atracurium (0.12 mg/kg) or vecuronium (0.02 mg/kg) were studied during 1% enflurane anesthesia until seven in each group qualified by achieving a maximal block between 85% and 97%. These patients were matched with each other and with patients who had received rocuronium. Seven groups of three patients (rocuronium, vecuronium, and atracurium) were obtained. The average difference in maximal block was less than 2% between matched patients. The ratio of dose used to achieve a similar final block suggests potency ratios of 1, 8.5, and 1.2 for rocuronium, vecuronium, and atracurium. Rocuronium's onset time (time from drug administration to 50%, 75%, and 90% of final block) was significantly faster than either of the other two muscle relaxants (P < 0.01). Time to 90% of final block was 1.35 min for rocuronium, 3.06 min for atracurium, and 3.71 min for vecuronium. Using these equipotent doses, atracurium also had a shorter time to develop neuromuscular block than vecuronium (P < 0.05). For these three intermediate duration neuromuscular blockers, speed of onset was inversely related to their potency, confirming a relationship that had been demonstrated for the long-acting drugs pancuronium, d-tubocuranine, and gallamine.

Adult↗
PubMed1993

Drug interactions of clinical significance with opioid analgesics.

Opioid analgesics and other drugs interact through multiple mechanisms, resulting in pharmacological effects that depend upon the pharmacodynamic action studied, the interacting agents and the route of administration. Many interactions result from induction or inhibition of the hepatic cytochrome P450 mono-oxygenase system. The elimination of opioids is largely dependent on hepatic metabolism, and drug interactions involving this mechanism can therefore be clinically significant. Antibiotics are often used concomitantly with opioids in patients undergoing medical or surgical procedures; the best documented metabolic interactions are with erythromycin and rifampicin (rifampin). Erythromycin increases and rifampicin decreases the effects of opioids. Cimetidine may increase the effects of opioids by increasing their duration of action; there have been no documented cases of interactions with ranitidine. Carbamazepine, phenytoin and the barbiturates can enhance the metabolism of opioids that rely on hepatic metabolism. Other pharmacokinetic interactions include those with benzodiazepines, tricyclic antidepressants, phenothiazines and metoclopramide. Interactions involving pharmacodynamic mechanisms are more common than pharmacokinetic ones. Such interactions are manifested clinically as as a summation (additive or synergistic) of similar or opposing pharmacological effects on the same body system. Idiosyncratic interactions also occur, the mechanisms of which have not been proven to be solely modulated by either pharmacokinetic or pharmacodynamic means. The knowledge of particular opioid-drug interactions, and the causative pharmacokinetic, pharmacodynamic, and idiosyncratic mechanisms, allows for the safer administration of opioid analgesics.

Analgesics↗
PubMed1993

Sufentanil disposition. Is it affected by erythromycin administration?

BACKGROUND: Because oral erythromycin administration has been associated with reduced elimination of alfentanil, suspicion has been raised about related opioids with similar metabolic pathways. A controlled crossover study of sufentanil pharmacokinetics was undertaken to resolve this issue. METHODS: Six subjects had measurements of plasma concentrations for 9 h after intravenous administration of sufentanil (3 micrograms/kg). Each subject was studied following no erythromycin (control) and after 1- and 7-day courses of erythromycin base. RESULTS: Plasma concentrations during the 9 h of measurement were similar before and after erythromycin. Terminal half-life and clearance and distribution volume did not change significantly among treatment groups. Values measured after 7 days of erythromycin were similar to controls. CONCLUSIONS: Prior administration of erythromycin does not alter pharmacokinetics of sufentanil in the 9 h following sufentanil administration. Thus, there are no apparent clinical consequences of prior or concomitant erythromycin administration in patients receiving sufentanil for procedures of 9 h or less.

Adult↗
PubMed1992

Time-course of respiratory depression after an alfentanil infusion-based anesthetic.

Postoperative respiratory depression after alfentanil administration has been described in several case reports. The effects of a prolonged alfentanil infusion on the CO2 response curve or cognitive function have not been studied. Twenty-one ASA physical status I or II patients were studied after a prolonged alfentanil infusion (> 90 min) to determine the incidence of postoperative respiratory depression, arterial O2 desaturation, and impairment of cognitive function. Each patient's recovery was observed at 30-min intervals for evidence of respiratory depression (utilizing the Read CO2 rebreathing method), desaturation by pulse oximetry (severe desaturation defined as arterial O2 saturation < 90%), and cognitive function (utilizing Trieger dot and digit substitution tests). Plasma samples were also examined for secondary elevations in alfentanil plasma concentrations. Significant depression of the CO2 response curve and cognitive function was found up to 1 h postoperatively. Arterial O2 desaturation was seen in 11 of 21 patients (52%). No correlation was found between arterial O2 desaturation and cognitive function scores or CO2 rebreathing results. Increased depression of the CO2 response curve was not necessarily associated with severe desaturation episodes. A secondary increase in plasma alfentanil concentration was detected in 5 of the 21 patients (24%), but these patients did not experience further depression of the CO2 response curve. We conclude that prolonged alfentanil administration may result in severe arterial O2 desaturation with significant depression of the hypercapnic respiratory drive during the first hour in the postanesthesia care unit, even though the majority of our patients were easily aroused in response to verbal stimuli.

Adult↗
PubMed1991

Comparative accuracies of a finger blood pressure monitor and an oscillometric blood pressure monitor.

A noninvasive blood pressure monitor (Finapres) that uses the methodology of Penaz to continuously display the arterial waveform from the finger has been introduced recently. The Finapres monitor overestimated systolic pressure by 5.8 +/- 11.9 mm Hg, while the Dinamap monitor underestimated systolic pressure by -6.9 +/- 9.2 mm Hg (P = 0.003). Dinamap mean and diastolic pressure biases were less than 2 mm Hg, while the Finapres biases for these variables were significantly greater (7.7 +/- 10.0 and 8.2 +/- 9.8 mm Hg, respectively). There was no difference in systolic or mean pressure precision between the two devices (approximately 10 mm Hg), but the diastolic precision of the Dinamap unit was superior to that of the Finapres. While in most patients the Finapres monitor provided continuous blood pressure data equivalent to the data from the radial artery, marked bias (greater than 15 mm Hg) was exhibited in 2 patients for all three pressure variables. Despite this bias, blood pressure changes were tracked closely in these 2 patients. We conclude that, in its current form, the Finapres monitor cannot be relied upon independently to accurately measure blood pressure in patients undergoing general anesthesia. Since the Dinamap monitor measures mean pressure reliably and accurately, we suggest that mean blood pressure values between the Finapres and Dinamap monitors be compared to guide one in interpreting Finapres data.

Adolescent↗
PubMed1991

Continuous noninvasive finger blood pressure during controlled hypotension. A comparison with intraarterial pressure.

The Finapres is a noninvasive monitor that continuously displays the arterial waveform, pulse rate, and systolic, mean, and diastolic blood pressure. We determined its bias (mean prediction error) and precision (mean absolute error), relative to directly measured radial arterial blood pressure, in 16 otherwise healthy patients undergoing spinal fusion surgery under hypotensive anesthetic techniques. Data were recorded during three contiguous epochs: 20 min of normotension; 30 min following the initiation of hypotension; 20 min of hypotension. The Finapres demonstrated a systolic, mean, and diastolic bias (+/- standard deviation) of 3.6 +/- 12.3, 5.2 +/- 10.8, and 8.3 +/- 9.4 mmHg, respectively. There were no significant differences in systolic bias among the epochs, whereas mean and diastolic bias were both greater during the hypotensive epoch, compared to the normotensive epoch. In 2 of the 16 patients, systolic and mean arterial pressure bias exceeded 20 mmHg. Finapres precisions of systolic, mean, and diastolic blood pressures were 9.8 +/- 9.0, 8.7 +/- 7.6, and 10.4 +/- 8.2 mmHg, respectively. Precisions among the epochs were not significantly different. When Finapres pressures were "corrected" by subtracting the baseline difference between Finapres and oscillometrically determined mean pressure, bias decreased significantly. The correction process did not improve precision. The Finapres closely tracked changes in blood pressure, even in the presence of a large bias. In most patients, the Finapres is a useful continuous noninvasive blood pressure monitor. Periodic calibration of the Finapres by the difference between Finapres and oscillometrically determined mean arterial pressure is recommended.

Adolescent↗
PubMed1990

Relationship between train-of-four ratio and first-twitch depression during neuromuscular blockade: a pharmacokinetic/dynamic explanation.

Fade, as measured by train-of-four, lags behind twitch depression during the initial phase of nondepolarizing neuromuscular blockade, i.e., the ratio of the fourth to first twitch height in a train (T4/T1) is greater at the onset of the block than during spontaneous recovery for the same level of first twitch depression. We believe that these data can be explained by picturing the muscle as having localized regions that respond much more slowly than the rest, leading to a delay in drug effect in that area, especially when the drug concentration rises rapidly as during bolus administration. This was modeled by computer as a muscle of 15 compartments distributed in a log-normal fashion according to equilibration rate. Experimental data consisting of the time course of first twitch and train-of-four ratio were fitted by nonlinear regression to the model. A good fit was obtained with a median equilibration time t1/2 of 3.3 min and a standard deviation of 2.1. The difference between train-of-four during onset and regression of block at the same level of first twitch depression was reproduced.

Computer Simulation↗
PubMed1989

Inhibition of alfentanil metabolism by erythromycin.

To investigate a possible connection between erythromycin administration and reduced elimination of alfentanil, a controlled crossover study of alfentanil pharmacokinetics was undertaken. Six subjects were monitored for alfentanil plasma levels for 8 hours after alfentanil was administered. These measurements were obtained after a 0-, 1-, and 7-day course of erythromycin. Elimination half-life increased significantly (p less than 0.01) after 7 days from the control value of 84.0 +/- 8.2 minutes to 131.4 +/- 43.5 minutes. Clearance was decreased significantly (p less than 0.05) from 3.9 +/- 0.8 ml/kg/min to 2.9 +/- 1.2 ml/kg/min after 7 days. Values after 1 day were intermediate. Distribution volume did not change significantly. Subjects differed sharply in their sensitivity to erythromycin. Because of the interaction between erythromycin and alfentanil, we recommend that patients who are receiving erythromycin should be given alfentanil in reduced amounts or should avoid the drug completely.

Adult↗
PubMed1989

Clinical pharmacology of pipecuronium bromide.

The neuromuscular blocking and cardiovascular effects of pipecuronium, in doses ranging 2-3 times its ED95, were evaluated in 46 patients during thiopental, fentanyl, N2O/O2 anesthesia. The neuromuscular blocking effect of pipecuronium was evaluated by recording of the mechanical twitch of the adductor pollicis muscle in response to stimulation of the ulnar nerve at the wrist. Heart rate, systolic and diastolic blood pressures, and cardiac output were non-invasively measured during the onset of the neuromuscular blockade and compared to a saline control group to separate the effect of anesthesia from those of pipecuronium. The mean +/- SD time from administration of pipecuronium to 90% suppression of the first twitch (T1) of the train-of-four was 2.6 +/- 0.8, 2.0 +/- 0.6, and 2.1 +/- 0.6 min following the 70 micrograms/kg, 85 micrograms/kg, and 100 micrograms/kg dose, respectively. There was no significant difference between the different doses of pipecuronium in the time to 90% suppression of T1. In general, all three doses of pipecuronium provided good to excellent intubating conditions within 3 minutes after its administration. The time from the administration of pipecuronium to 5% recovery of T1 was 52.3 +/- 18.2 min in the group given 70 micrograms/kg. This was significantly longer in patients given 85 micrograms/kg (71.9 +/- 15.7 min) or 100 micrograms/kg (71.8 +/- 22.1 min). Times to the start of recovery of T1 and to 25% recovery of T1 showed a similar significant pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Incomplete reversal of pancuronium neuromuscular blockade by neostigmine, pyridostigmine, and edrophonium.

Three clinically used anticholinesterases--neostigmine, pyridostigmine, and edrophonium--were tested for their ability to reverse two levels (60% and 95%) of neuromuscular blockade produced by pancuronium. A controlled in vitro environment of the rat diaphragm-phrenic nerve system was used for the studies. Concentrations of anticholinesterases spanned the clinical range and were extended beyond to establish dose-response curves. Neostigmine was the most potent reversal drug (ED50 for 95% block 5.5 +/- 4 nM), followed by pyridostigmine (0.27 +/- 0.06 microM) and edrophonium (2.1 +/- 0.05 microM). The three drugs were equally effective at reversal of block and fade as measured by train-of-four stimulation. The dose-response curves for all three drugs showed a ceiling effect for reversal of tension and fade. Supraclinical concentrations of drug did not effect complete reversal, especially at 95% block. High concentrations of anticholinesterase led to randomly appearing hyperactivity manifested by spontaneous twitching and repetitive firing with severe fade on stimulation.

Animals↗
PubMed1984

ED50 of alfentanil for induction of anesthesia in unpremedicated young adults.

This study determined the ED50 and ED90 of alfentanil for unconsciousness and anesthesia. A bolus of alfentanil was given to 28 healthy unpremedicated adults undergoing gynecologic or orthopedic procedures in one of four dosages: 100, 150, 200, or 250 micrograms/kg. Three indicators of induction were assessed 90 s later: eyelid reflex, response to verbal commands to breathe, and response to placement of a nasopharyngeal airway. Succinylcholine, given at 90 s, was followed by tracheal intubation 1 min later. From probit analysis, the ED50 and ED90 for loss of voice response were 92 and 111 micrograms/kg, respectively, and for loss of nasopharyngeal airway response, 111 and 169 micrograms/kg. A high incidence of chest wall rigidity (75%) and movements of the limbs (54%) or eyes (25%) was seen. There were statistically significant increases of the heart rate prior to stimulation and of both the heart rate (21% rise) and systolic blood pressure (10% rise) from control to the peak value following intubation. Differences between alfentanil doses were not significant. Naloxone was required in 36% of patients for end-tidal PCO2 greater than 48 mmHg at emergence from anesthesia; no patient required additional naloxone. Nausea or vomiting occurred in 39% of all subjects. Two patients recalled placement of the nasopharyngeal airway. We conclude that alfentanil is an anesthetic, and its ED50 (analogous to MAC of inhalational agents) is 111 micrograms/kg. The blood pressure and heart rate responses to laryngoscopy and intubation were modest after doses that allowed for extubation as early as 51 min after induction.

Adjuvants, Anesthesia↗
PubMed1984

Alfentanil as an anesthetic induction agent--a comparison with thiopental-lidocaine.

Alfentanil (0.175 mg/kg) and a combination of thiopental (3-4 mg/kg) and lidocaine (1.5 mg/kg) during anesthetic induction were compared. Each was administered rapidly to eight patients with cardiovascular disease (average age, 64 yr), followed by succinylcholine (1.5 mg/kg) for laryngoscopy and intubation. Chest wall rigidity or flexor spasm of arm and jaw were seen transiently in 7 of 8 patients receiving alfentanil. Both drugs led to decreases in mean arterial pressure averaging 31 mm Hg (P less than 0.01). In patients given thiopental-lidocaine, intubation led to a 28 mm Hg (P less than 0.01) increase over control in arterial pressure and a 10 beats . min-1 increase in heart rate (P less than 0.01). In patients given alfentanil, after intubation arterial pressure returned to levels no different from control and the heart rate remained stable. Five of the patients given alfentanil required a single dose of naloxone (0.08-0.15 mg) to achieve a PCO2 less than 50 torr at the end of surgery. Rapidly administered alfentanil blunted the cardiovascular response to intubation but decreased arterial pressure as much as thiopental-lidocaine.

Aged↗