Search PubMed⌕ Search

Biomedical subjects

N T Smith

Publications and source records attributed to N T Smith.

At least 19 recordsLinked to original sources
PubMed1995

A role for CNS alpha-2 adrenergic receptors in opiate-induced muscle rigidity in the rat.

A number of potential neurochemical mediators of opiate-induced muscle rigidity have been proposed based on the results of systemic drug studies and on knowledge of the brain sites implicated in opiate rigidity. The effects of i.c.v. pretreatment with selected opioidergic, alpha adrenergic and serotonergic drugs on muscle rigidity induced with systemic injection of the potent opiate agonist alfentanil (ALF) were investigated in spontaneously ventilating rats. The opiate antagonist methylnaloxonium (MN; 0.2-14 nmol), alpha-2 adrenergic agonists dexmedetomidine (DEX; 0.4-42 nmol) or 2-(2,6-diethylphenylamino)-2-imidazoline hydrochloride (ST91; 4-400 nmol), alpha-1 adrenergic antagonist prazosin (PRZ; 7-70 nmol) or serotonergic antagonist ketanserin (KET; 18-550 nmol) were injected i.c.v. (10 microliters) and ALF (500 micrograms/kg s.c.) was administered 10 min later. S.c. electrodes were used to record gastrocnemius electromyographic activity. Both MN and DEX dose-dependently and potently antagonized ALF-induced rigidity. ST91 produced shorter-lived, less profound, antagonism of ALF rigidity. PRZ, at the highest dose tested, produced a delayed and modest reduction in ALF rigidity. A large, non-selective, dose of KET incompletely attenuated ALF rigidity. These results lend support to the hypothesis that central opioid and alpha-2 adrenergic receptors mediate opiate-induced muscle rigidity in the rat.

Adrenergic alpha-Agonists↗
PubMed1995

Wakeful response to command indicates memory potential during emergence from general anesthesia.

OBJECTIVE: An important aspect of assessing anesthetic depth is determining whether a patient will remember events during surgery. We looked for a clinical sign that would indicate a patient's potential for memory formation during emergence from anesthesia. A clinical sign indicating memory potential could be a useful endpoint for measuring the performance of anesthetic depth monitors and for titrating administration of anesthetic agents. METHODS: We evaluated patients' responses to commands to open the eyes, squeeze the hand four times, and count 20 numbers. These responses were correlated with results on recall, cued recall, and multiple-choice memory tests. MAIN RESULTS: Patients did not have evidence of memory formation until they sustained wakefulness sufficiently long to complete at least four hand squeezes or count four numbers. Of 28 patients, 13 (46%) with this sustained wakeful response had memory. Of 22 patients, 0 (0%) had evidence of memory formation when they demonstrated a brief wakeful response, defined as being responsive to command but unable to complete more than one hand squeeze or count, or an intermediate response, defined as two or three hand squeezes or counts. CONCLUSIONS: We conclude that a brief wakeful response to command indicates that a patient is unlikely to form memories, while a sustained wakeful response indicates that a patient may form memories. Thus, a patient's wakeful response to command could be a useful indicator of potential for memory.

Adult↗
PubMed1995

Brief wakeful response to command indicates wakefulness with suppression of memory formation during surgical anesthesia.

OBJECTIVE: In a previous study of patients emerging from anesthesia following surgery, we found that a brief wakeful response to command of an eye opening or single hand squeeze or count was not associated with memory formation, while the response of four hand squeezes or counts was associated with memory. We wanted to determine the anesthetic requirements for obtaining this brief wakeful response endpoint during surgery and to determine if memory occurred at this endpoint during surgical anesthesia. METHODS: Six different combinations of isoflurane, 70% N2O, and fentanyl were administered to 326 patients undergoing pelvic laparoscopy. After insertion of the trocar, anesthesia was reduced while patients were given verbal commands, and they were observed for movement responses to surgery and to command. Patients were classified as either not arousing, arousing with a movement response to surgery, or arousing with a wakeful response to command. For the patients who aroused, we calculated the percentage of arousal responses that were wakeful responses to command. The effect of fentanyl dosage upon the percentage of arousal responses that were wakeful responses to command was determined by using a Mann-Whitney test to compare a group of patients receiving fentanyl 2 micrograms/kg or less, with a group receiving fentanyl 4 micrograms/kg. In a subset of 39 patients, the potential for memory formation was evaluated by presenting a target sound to 29 patients during a period of either no arousal, movement response to surgery, or wakeful response to command; for a control group of 10 patients, no target sound was presented. All 39 patients were tested for memory of the target sound; the results from each group receiving a target sound were compared with the results of the control group, using a Mann-Whitney test. MAIN RESULTS: A total of 68 patients aroused with either a movement response or a wakeful response to command. Wakeful responses occurred with only 1 of 39 patients (3%) receiving fentanyl 2 micrograms/kg or less; but, wakeful responses occurred with 17 of 29 patients (59%) receiving fentanyl 4 micrograms/kg. The difference between the groups was significant at p = 0.01. None of the 68 patients had recall of intraoperative events or unpleasant dreams. None of these patients who were in the multiple-choice memory subset recalled the target sound. There were no statistically significant differences on the multiple-choice memory test between the groups presented with the target sound and the control group. Patient anecdotes suggested that some patients may have had memory of the target sound; but, memory was no more likely in patients with a brief wakeful response to command than in those who responded with a movement to surgical stimulation or those who did not have an arousal response. CONCLUSIONS: A brief wakeful response to a command of opening the eyes or squeezing the hand was not associated with increased memory formation during surgery. A brief wakeful response to command was found during surgery when patients received fentanyl 4 micrograms/kg; but it was rarely found at fentanyl dosages of 2 micrograms/kg or less.

Adolescent↗
PubMed1992

Cardiovascular simulation using a multiple modeling method on a digital computer--simulation of interaction between the cardiovascular system and angiotensin II.

A cardiovascular system model that simulates interactive responses to drugs has been developed on a small digital computer. The overall model basically consists of three models. The first is a momentum transport model that represents relations between blood pressure and flow in the cardiovascular system. In this model, the cardiovascular system is divided into 14 components and modeled by using equivalent electrical circuits. The second is a mass transport model comprising 14 compartments corresponding to the respective components of the cardiovascular system. This model represents the distribution of the administered drug in the various cardiovascular components. The third is an interaction model that represents the relationships between the momentum and mass transport models. This model causes variations in the resistance and capacitance parameters of the momentum transport model as a function of the current drug concentrations in the appropriate compartments of the mass transport model. The capacitances representing the ventricles are varied in a time-dependent fashion to simulate the beat of the heart. Simulation is performed by using the Euler method to solve a system of 28 ordinary differential equations governing the momentum and mass transport models on a 32-bit microcomputer, a Macintosh II. The model was assessed by performing two demonstrations of the cardiovascular response to the vasopressor angiotensin II (AT II). They first examined the interaction between the cardiovascular system and AT II. The effect of AT II on the cardiovascular system was incorporated into the interaction model. Administration of AT II as a constant infusion (200 micrograms/hr) resulted in an elevation of mean arterial pressure from approximately 100 to 150 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

Improved safety and efficacy in adaptive control of arterial blood pressure through the use of a supervisor.

This paper presents a dual approach to adaptive control of arterial blood pressure using sodium nitroprusside. In the clinical environment, a controller must be aggressive to achieve specific step response characteristics (less than 10 min settling time, less than 10 mm Hg overshoot), yet conservative enough to prevent overreactions to large disturbances, which are common in both the operating room and the intensive care unit. These mutually exclusive requirements make it difficult to design a closed-loop controller for this environment. To prevent possible overreactions, while maintaining proper step response, an aggressive adaptive controller has been designed to achieve the desired step response, and a SUPERVISOR has been designed around the adaptive controller to limit potential overreactions in the presence of disturbances. Simulations and dog experiments demonstrate the potential for increased safety and efficacy using this dual approach to the control of a complex physiological system.

Animals↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗