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Biomedical subjects

N T Smith

Publications and source records attributed to N T Smith.

At least 37 records · Page 2Linked to original sources

Supervisory adaptive control of arterial pressure during cardiac surgery.

A supervisory adaptive controller has been designed for the closed-loop control of mean arterial pressure during cardiac surgery, using sodium nitroprusside. This controller consists of a pole-placement and proportional-plus-integral feedback regulator, multiple-model adaptation, and a supervisor. The pole-placement and proportional-plus-integral regulator was designed to meet aggressive step response characteristics. Multiple-model adaptation was chosen to ensure rapid and stable adjustments for changes in key patients parameters. The supervisor was designed to provide safety and efficacy of control during disturbances that are common during cardiac surgery. We studied the ability of this supervisory adaptive controller to regulate arterial pressure during cardiac surgery on nineteen patients. The controller, through the action of the supervisor, detected and responded appropriately to the great majority of disturbances. This study demonstrated that supervisory adaptive control has the potential to provide clinically acceptable regulation of arterial pressure.

Cardiac Surgical Procedures↗

Brain sites mediating opiate-induced muscle rigidity in the rat: methylnaloxonium mapping study.

Previous work has demonstrated that direct injections of methylnaloxonium (MN), a hydrophilic quaternary opiate antagonist, in the area of the nucleus raphe pontis (RPn) significantly attenuated alfentanil-induced muscle rigidity in the rat. To extend these observations and to explore further the regions important for opiate-induced rigidity, rats were implanted with chronic guide cannulae aimed at discrete brain sites with an emphasis on the region from the periaqueductal grey (PAG) to the RPn. Each animal was pretreated by a blinded observer with an intracerebral injection of MN (125 ng total dose) or saline, and electromyographic (EMG) activity was recorded from the gastrocnemius muscle. Alfentanil (ALF; 500 micrograms/kg) was then administered subcutaneously and the magnitude of tonic EMG activity was assessed as a measure of hindlimb rigidity. The administration of MN into the pontine raphe nucleus (RPn) and also into the more lateral nucleus reticularis tegmenti pontis significantly attenuated ALF rigidity compared with saline-pretreated controls. Within the midbrain, MN selectively reversed rigidity when injected into the periaqueductal grey (PAG). The dorsal PAG appeared to be a more important site than the ventral PAG. There was no significant effect on ALF rigidity of MN injections into brain regions between the ventral PAG and the RPn while MN injections into the deep layers of the superior colliculus, lateral to the dorsal PAG, partially attenuated ALF rigidity. In contrast, rigidity was not consistently reversed after MN injections into the basal ganglia, the dorsal superior colliculus, or the region of the decussation of the dorsal tegmentum. This study provides strong evidence that nuclei of the reticular formation, specifically the PAG, raphe pontis, and reticularis tegmenti pontis that are known to play a role in other opioid-mediated behaviors, are important in opiate-induced muscle rigidity in the rat. These results could have implications for the prevention of this undesirable effect of high-dose opiate administration.

Alfentanil↗

Recognition accuracy with a voice-recognition system designed for anesthesia record keeping.

We tested on three occasions, with anesthetists as subjects, the accuracy of two voice-recognition systems designed for anesthetic record keeping. Initially, a prototype system was tested (10 subjects); several years later the resulting commercial system was tested in a quiet environment (11 subjects) and in noisy operating rooms (10 subjects). For each test an anesthetist first trained the system to recognize his or her voice by reading aloud a list of common anesthetic terms. To determine recognition accuracy, the percentage of words recognized correctly by the computer, each subject repeated the vocabulary words ten times. Although accuracy was similar during the three tests, it was slightly higher with the laboratory test (mean percent of words recognized correctly, 96.5%; range of accuracy for individual anesthetists, 91.6 to 98.8%) than with the prototype test (95.9%; range, 89.1 to 99.6%). Accuracy was lowest with the operating room test (95.3%; range, 87.8 to 98.4%). Twenty-four words caused particular difficulty during the laboratory test and were eliminated from the vocabulary of the subsequent operating room test. Omitting these 24 words from the laboratory vocabulary list allowed a more nearly direct comparison with the results from the operating room list; recognition accuracy improved in the former to 97.5% (range, 92.1 to 98.9%). Two anesthetists--one each from the laboratory and operating room tests--performed poorly, and eliminating their scores changed the respective overall scores to 98.2% (range, 96.7 to 98.9%) and 96.5% (range, 94.3 to 98.4%). Thus, the corrected difference between the laboratory accuracy and the operating room accuracy was 1.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Pulse oximetry and finger blood pressure measurement during open-heart surgery.

Pulse oximeter arterial hemoglobin oxygen saturation (SpO2) and finger arterial pressure (FINAP) were continuously monitored before, during, and after cardiopulmonary bypass in 15 male patients. SpO2 was monitored simultaneously with two pulse oximeters, a Nellcor N-100 and an Ohmeda Biox III. The readings obtained from the two pulse oximeters were compared with arterial blood measurements obtained using a CO-oximeter. FINAP was monitored by a prototype device (Finapres) based on the Penaz volume-clamp method. FINAP was correlated with intraarterial pressure (IAP). Both pulse oximeters functioned well before cardiopulmonary bypass. The correlations with CO-oximeter values were 0.927 for the N-100 and 0.921 for the Biox III. Immediately after the onset of cardiopulmonary bypass, the N-100 pulse oximeter stopped displaying values. The Biox III pulse oximeter continued to display values during the cardiopulmonary bypass period; the correlation with CO-oximeter values was 0.813. After cardiopulmonary bypass, the N-100 began displaying values in 2 to 10 minutes. After cardiopulmonary bypass the correlation with CO-oximeter values was 0.792 for the N-100 and 0.828 for the Biox III pulse oximeter. The Finapres finger blood pressure device functioned well in 13 of 15 patients before cardiopulmonary bypass. The mean bias +/- precision of FINAP-IAP for mean pressure was 8.3 +/- 10.2 mm Hg (SD) and the correlation coefficient was 0.814. During cardiopulmonary bypass, the Finapres device functioned well in 10 of 15 patients. The mean bias precision of FINAP-IAP, for mean pressure in these 10 patients was 6.6 +/- 8.7 mm Hg and the correlation coefficient was 0.902.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Aging and alfentanil disposition in healthy volunteers and surgical patients.

We studied the pharmacokinetic disposition of alfentanil in 20 volunteers and in 15 surgical patients 20-72 years old. Pharmacokinetic disposition was first order and was well described by a two-compartment open model. Central-compartment volume of distribution was 0.131 +/- 0.087 L.kg-1 (mean +/- SD) in young healthy volunteers and decreased modestly with increasing age (r = -0.32, P less than 0.05). However, apparent volume of distribution at steady-state, 0.404 +/- 0.205 L.kg-1 for the whole study cohort, was not age-related. Plasma clearance of alfentanil in young healthy subjects, 9.3 +/- 6.3 ml.kg-1.min-1, also showed an inverse relationship with age (r = -0.54, P less than 0.001), and was not affected by surgical stress in subjects older than 60 years. Cigarette smoking and sex of the subjects did not contribute to interindividual differences in the kinetic disposition of this drug. Our finding that interindividual differences in disposition of alfentanil were the least in older subjects suggests that its pharmacological effects related to pharmacokinetic disposition should be most predictable in the elderly.

Adult↗

Seizures during opioid anesthetic induction--are they opioid-induced rigidity?

The tape recorded EEGs of 127 patients anesthetized with large doses of opioids were retrospectively analyzed for evidence of opioid-induced seizures, and in particular, correlated with movements that occurred during induction and could be clinically interpreted as seizures. Bilateral EEG leads in patients receiving fentanyl (20), sufentanil (20), or alfentanil (87) were recorded. Forty-six of these patients from all opioid groups manifested intense rigidity, as assessed both clinically and by EMGs recorded from eight muscles in 69 of the patients receiving alfentanil. This intense rigidity often resembled seizures, in that the phenomenon entailed severe stiffness of both limbs and trunk, with an explosive onset of myoclonic limb movements, and associated vertical nystagmus. Electroencephalographic observations were extensive, entailing 69 h of paper recordings played back from the tapes, at paper speeds of 30 or 60 mm/s, with detailed annotations from the voice track. These paper recordings were examined in detail independently by three of the investigators, who were unaware of the clinical phenomena that had occurred. The only observed EEG activity that could have been interpreted as epileptiform consisted of small sharp waves related to muscle activity or other artifact. The EEG never indicated seizure activity during these drug-induced movements and rigidity. Reports of opioid-induced seizures are reviewed and a set of criteria is offered to help achieve future consistency and credibility in evaluating this phenomenon. The available evidence does not support the existence of opioid-induced seizures in the clinical setting.

Alfentanil↗

Localization of brainstem sites which mediate alfentanil-induced muscle rigidity in the rat.

Previous work has demonstrated that direct injections of methylnaloxonium (MN), a relatively lipophobic quaternary opiate antagonist, in the area of the nucleus raphe pontis (RPn) significantly attenuated alfentanil-induced rigidity. It was hypothesized that other hindbrain sites, particularly the other raphe nuclei, might play a role in this rigidity. Therefore, a study was performed in which 57 rats, divided into four groups, were implanted with chronic guide cannulae directed at brain sites anterior, lateral, or posterior to the RPn. After each animal was pretreated with intracerebral injections of MN, alfentanil (0.5 mg/kg) was administered subcutaneously. Electromyographic activity was recorded from the gastrocnemius muscle as a measure of hindlimb rigidity. Each animal was subsequently injected at 4 to 5 day intervals with MN two additional times at sites 1 and 2 mm deeper, respectively, than the initial injection. Data were thus obtained on animals treated with either MN or saline at 3 successive histologically identified sites which were either anterior, lateral or posterior to the RPn. The administration of MN into two specific sites in the region just lateral to the nucleus raphe pontis significantly [F(1,38) = 18.68 and 5.02 respectively, p less than 0.05] reversed the rigidity produced by systemic alfentanil administration. There was a weak effect of MN injections anterior to the RPn but this could not be localized to any one site. These results suggest that discrete brainstem regions involved in opiate action can be sensitively and selectively identified by direct intracranial injections of a lipophobic opiate antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Alfentanil↗

Prebypass hemodynamic stability of sufentanil-O2, fentanyl-O2, and morphine-O2 anesthesia during cardiac surgery: a comparison of cardiovascular profiles.

Cardiovascular responses and the need for intervention with vasoactive agents were measured prospectively in a randomized study of 50 adult patients receiving sufentanil (n = 20), fentanyl (n = 20), or morphine (n = 10) anesthesia for cardiac surgery. Measurements were recorded and compared during induction and prebypass at intervals during which airway or surgically induced stress responses were likely to be greatest. Randomized, double-blinded doses of opioids were administered slowly and titrated according to clinical responses (hemodynamics) and the electroencephalogram. Mean doses were as follows: from induction until time of incision, sufentanil, 9.1 microg/kg; fentanyl, 58 microg/kg; and morphine, 2.5 mg/kg; and total dose for surgery; sufentanil, 18.9 microg/kg; fentanyl, 95.4 microg/kg; and morphine, 4.4 mg/kg. Equi-anesthetic depth in patients receiving sufentanil or fentanyl was confirmed by continuous electroencephalographic monitoring. Patients anesthetized with sufentanil and fentanyl showed marked cardiovascular stability and rarely responded to stimuli. Systolic arterial pressure, mean arterial pressure, heart rate, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, stroke volume index, and stroke work index values were similar in the two groups. Patients receiving morphine experienced large changes in several variables. Pharmacologic intervention was made when systolic arterial pressure deviated more than 30% from pre-event values and was uncontrolled by additional opioids. Interventions were necessary more often in patients receiving morphine (nine of ten) or fentanyl (12 of 20) than in patients receiving sufentanil (six of 20), P < 0.05. Results from this study suggest that morphine is a relatively unsatisfactory anesthetic, while sufentanil and fentanyl, at equi-anesthetic depths, provide stable and satisfactory hemodynamics.

Aged↗

Noninvasive continuous blood pressure measurement from the finger: optimal measurement conditions and factors affecting reliability.

We recorded finger arterial blood pressure (FINAP) in 50 male patients during various types of surgical operations. Three different types of cuffs were used on four fingers of each patient. Measurements were made by the arterial volume-clamp method of Penaz. The FINAP measurements were compared with pressure data obtained ipsilaterally from a radial artery catheter-transducer system (intraarterial pressure [IAP]) to find optimal recording conditions and to document factors affecting FINAP readings. The thumb, with a specially designed cuff, gave the most accurate results. The mean FINAP - IAP difference for the thumb was -4.8 mm Hg for systolic pressure, 1.49 mm Hg for diastolic pressure, and 0.29 mm Hg for mean pressure. The differences were statistically significant for systolic and diastolic pressure but not for mean pressure. The regression slope for thumb systolic FINAP/IAP was 0.979, that for thumb diastolic FINAP/IAP was 0.963, and that for mean thumb FINAP/IAP was 0.996, whereas the intercepts were 7.499 for systolic pressure, 0.802 for diastolic pressure, and 0.083 for mean pressure. The correlation coefficients were 0.945 (systolic), 0.884 (diastolic), and 0.949 (mean). The correlation coefficients with the other fingers ranged from 0.502 to 0.922 for systolic pressure, 0.757 to 0.932 for diastolic pressure, and 0.767 to 0.892 for mean pressure. The slopes for the various finger-cuff combinations ranged from 0.537 to 0.996, and the intercepts ranged from 0.083 to 32.387 from mean pressure. In 3 patients (6%) the FINAP measurement was not possible because of insufficient peripheral circulation. In 9 other patients (18%) the FINAP measurements were not accurate during some periods of time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Computer model analysis of the radial artery pressure waveform.

Simultaneous measurements of aortic and radial artery pressures are reviewed, and a model of the cardiovascular system is presented. The model is based on resonant networks for the aorta and axillo-brachial-radial arterial system. The model chosen is a simple one, in order to make interpretation of the observed relationships clear. Despite its simplicity, the model produces realistic aortic and radial artery pressure waveforms. It demonstrates that the resonant properties of the arterial wall significantly alter the pressure waveform as it is propagated from the aorta to the radial artery. Although the mean and end-diastolic radial pressures are usually accurate estimates of the corresponding aortic pressures, the systolic pressure at the radial artery is often much higher than that of the aorta due to overshoot caused by the resonant behavior of the radial artery. The radial artery dicrotic notch is predominantly dependent on the axillo-brachial-radial arterial wall properties, rather than on the aortic valve or peripheral resistance. Hence the use of the radial artery dicrotic notch as an estimate of end systole is unreliable. The rate of systolic upstroke, dP/dt, of the radial artery waveform is a function of many factors, making it difficult to interpret. The radial artery waveform usually provides accurate estimates for mean and diastolic aortic pressures; for all other measurements it is an inadequate substitute for the aortic pressure waveform. In the presence of low forearm peripheral resistance the mean radial artery pressure may significantly underestimate the mean aortic pressure, as explained by a voltage divider model.

Blood Pressure↗

Ketanserin pretreatment reverses alfentanil-induced muscle rigidity.

Systemic pretreatment with ketanserin, a relatively specific type-2 serotonin receptor antagonist, significantly attenuated the muscle rigidity produced in rats by the potent short-acting opiate agonist alfentanil. Following placement of subcutaneous electrodes in each animal's left gastrocnemius muscle, rigidity was assessed by analyzing root-mean-square electromyographic activity. Intraperitoneal ketanserin administration at doses of 0.63 and 2.5 mg/kg prevented the alfentanil-induced increase in electromyographic activity compared with animals pretreated with saline. Chlordiazepoxide at doses up to 10 mg/kg failed to significantly influence the rigidity produced by alfentanil. Despite the absence of rigidity, animals that received ketanserin (greater than 0.31 mg/kg i.p.) followed by alfentanil were motionless, flaccid, and less responsive to external stimuli than were animals receiving alfentanil alone. Rats that received ketanserin and alfentanil exhibited less rearing and exploratory behavior at the end of the 60-min recording period than did animals that received ketanserin alone. These results, in combination with previous work, suggest that muscle rigidity, a clinically relevant side-effect of parenteral narcotic administration, may be partly mediated via serotonergic pathways. Pretreatment with type-2 serotonin antagonists may be clinically useful in attenuating opiate-induced rigidity, although further studies will be necessary to assess the interaction of possibly enhanced CNS, cardiovascular, and respiratory depression.

Adjuvants, Anesthesia↗

The role of the nucleus raphe pontis and the caudate nucleus in alfentanil rigidity in the rat.

Attempts to eliminate or reduce the rigidity induced with high-dose narcotic anesthesia in the operating room have been only partially successful. Previous investigations of opioid receptor sites mediating this rigidity have implicated two central regions: the nucleus raphe pontis (NRP) within the reticular formation and the caudate nucleus (CN) within the basal ganglia. The present study used systemically administered alfentanil (ALF), a potent, short-acting fentanyl analog, and intracerebrally infused methylnaloxonium (MN), a quaternary derivative of naloxone, to elucidate further the functional role of the NRP and CN in rigidity. ALF (0.5 mg/kg s.c.) produced a reliable model of rigidity, as documented by gastrocnemius electromyography. The onset of this rigidity was within 60 s of ALF administration, with a total duration of approximately 40-50 min. Intracerebroventricular (i.c.v.) injections of 2.0 or 4.0 micrograms of MN 15 min prior to ALF treatment prevented rigidity, while 0.125 or 0.5 microgram had no significant effect on rigidity. MN injected directly into the NRP at doses as low as 0.125 microgram significantly antagonized ALF-induced rigidity, while injections of MN into the caudate nucleus at doses as high as 4.0 micrograms failed to antagonize ALF-induced rigidity. These observations demonstrate that injection of MN into the NRP is at least 16-fold more effective in blocking ALF-induced rigidity than MN injected into the ventricle and, more importantly, at least 32-fold more effective than MN injected into the CN. The results suggest that the NRP may be an important site for the neural control of muscular rigidity associated with high-dose narcotic administration.

Alfentanil↗