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Biomedical subjects

A R Bjorksten

Publications and source records attributed to A R Bjorksten.

54 records · Page 3Linked to original sources
PubMed1994

Oxygen supplementation during upper gastrointestinal endoscopy: a comparison of two methods.

The optimal method of oxygen supplementation during upper gastrointestinal endoscopy has not been clearly defined. The aim of this study was to compare oxygen supplementation via nasal prongs with that via a catheter passed into the low oropharynx to eliminate the effect of mouth breathing. Patients were stratified according to the American Society of Anesthesiologists (ASA) classification of physical status into lower-risk (ASA 1 and 2) and higher-risk (ASA 3) groups. The lower-risk group received intranasal, intrapharyngeal, or no oxygen supplementation, and higher-risk patients received either intranasal or intrapharyngeal oxygen. Continuous arterial oxygen saturation (SpO2) was recorded, using a pulse oximeter, before and during endoscopy. Critical desaturations (SpO2 < or = 90%), minimum SpO2 during endoscopy, and maximum desaturation from the baseline oxygen on air, were evaluated. There was no significant difference in the number of patients desaturating, minimum SpO2, or in the maximum desaturation from the baseline between the groups receiving intranasal or intrapharyngeal oxygen supplementation. In lower-risk patients receiving no supplementary oxygen (n = 27), ten patients (37%) desaturated, compared with one of 52 patients (2%) receiving supplementary oxygen (p < 0.001). There was also a significant difference between these groups in the minimum SpO2 (91% vs 97%, p < 0.001) and the maximum desaturation from the baseline (-5.2% vs +0.7%, p < 0.001) during endoscopy. We conclude that the intranasal and intrapharyngeal methods of oxygen supplementation are of similar efficacy, and that supplementary oxygen significantly decreases the incidence of critical arterial oxygen desaturation that occurs even in healthy patients undergoing upper gastrointestinal endoscopy.

Administration, Intranasal↗
PubMed1994

Propofol causes a dose-dependent decrease in the thermoregulatory threshold for vasoconstriction but has little effect on sweating.

BACKGROUND: Volatile anesthetics increase the core temperature required to trigger sweating and decrease the core temperature required to trigger vasoconstriction. However, little is known about the effects of intravenous anesthetics on thermoregulation. We therefore tested the hypothesis that propofol increases the sweating threshold and decreases the vasoconstriction threshold, thereby increasing the inter-threshold range (core temperatures not triggering autonomic thermoregulatory responses). The study was conducted using a new model in which thermal manipulations were restricted to insensate skin, and sensate skin temperature was controlled. METHODS: Six healthy, male volunteers were studied on 3 randomly ordered days: no propofol, target propofol blood concentration 2 micrograms/ml, and target blood propofol concentration 4 micrograms/ml. Each day, epidural anesthesia (approximately T11 level) was induced, using 2% 2-chloroprocaine (one volunteer received bupivacaine). Thermal manipulations were confined to the legs, and we attempted to maintain upper-body (sensate) skin temperature constant. Propofol was infused by a computer-controlled infusion pump. Volunteers were heated until sweating was observed, then cooled until fingertip vasoconstriction was observed. The sweating threshold was defined as the tympanic membrane temperature triggering sustained evaporative heat loss > 40 g.m-2.h-1. Similarly, the vasoconstriction threshold was defined as the tympanic membrane temperature triggering a sustained reduction in fingertip blood flow to < 0.25 ml/min. Central venous blood was assayed for propofol blood concentration. RESULTS: Increasing propofol concentration produced a linear decrease the vasoconstriction threshold (slope = -0.53 +/- 0.34 degrees C.microgram-1.ml-1; R2 = 0.98 +/- 0.04 [mean +/- SD]), but had little effect on the sweating threshold. The inter-threshold range was 0.51 +/- 0.46 degrees C during epidural anesthesia alone, and increased significantly, by 0.49 +/- 0.31 degrees C.microgram-1.ml-1 during propofol administration. CONCLUSIONS: Like volatile anesthetics, propofol reduces the vasoconstriction threshold and increases the inter-threshold range. However, propofol differs in leaving the sweating threshold unchanged.

Adult↗
PubMed1993

Pharmacodynamics of atracurium in clinical practice: effect of plasma potassium, patient demographics, and concurrent medication.

To determine which factors influenced the pharmacodynamics of atracurium in clinical practice, the steady-state plasma concentration of atracurium for 90% paralysis (Cpss90) was measured in 100 adult patients. Neuromuscular block was maintained at 88%-92% of the control response by adjusting the target concentration being delivered by preprogrammed intravenous atracurium infusion. The Cpss90 was measured empirically from plasma samples taken when the block had been stable for 15 min with no adjustment in the infusion rate for 20 min. To describe how factors influenced the Cpss90 of atracurium, a model was developed by multiple stepwise linear regression analysis. Influencing variables retained in the final model were plasma potassium concentration, intraoperative administration of gentamicin, and premedication with papaveretum and hyoscine. The model predicted that the Cpss90 of atracurium would decrease with decreasing serum potassium according to the relationship log10(Cpss90) = 2.380 + 0.171 x [K mmol/L] (n = 100; ANOVA, P < 0.001). Intraoperative administration of gentamicin modified this relationship resulting in a 25.1% decrease in the predicted Cpss90 (n = 15; ANOVA, P < 0.001). Premedication with papaveretum and hyoscine also modified this relationship resulting in a 21.2% decrease in predicted Cpss90 (n = 30; ANOVA, P < 0.001). The model predicted that administration of both would decrease the Cpss90 by 41.0%. Patients aged > or = 70 yr had a slight, but statistically insignificant, increase in the Cpss90 compared to younger adult patients. No other factor was found to influence the Cpss90, including patient sex, body fluid, and other drugs administered in the perioperative period, including calcium channel antagonists and ranitidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effect of body build on the clearance of atracurium: implication for drug dosing.

To determine factors that influenced the clearance (Cl) of atracurium, 80 adult patients of varying body build were given an atracurium infusion according to a predetermined profile, which was scaled by lean body mass (LBM). Cl was estimated at 50-60 min by the constant infusion rate required to maintain the steady-state plasma concentrations. The efficacy of scaling the absolute Cl estimate by body build variables, in which the absolute Cl estimate is divided by the body build variable to achieve similar scaled estimates in all patients, was assessed by the bias and precision of the individual scaled Cl estimates to those in patients with a "normal" body build (23%-27% body fat). The efficacy of scaling the dose of atracurium by differing body build variables to achieve similar plasma concentrations was also assessed by bias and precision, in which the plasma concentrations from an infusion scaled by other body build variables were generated by linear simulation. Body size, as quantified by LBM, total body mass (TBW), height, and body surface area, had a significant influence on Cl, with the effect best described by LBM (respective R2, 0.487, 0.368, 0.265, 0.445). No other factors could be identified, including blood pH, serum creatinine, and drugs given during the peroperative period. The efficacy of scaling Cl by TBW (absolute Cl estimate divided by patient TBW) to achieve similar estimates in all patients was poor; Cl.TBW estimates varied inversely with patient body fat content and resulted in obese patients having smaller estimates, a mean bias of -29%, compared with those in patients with a normal body build (P = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Stability of fentanyl, bupivacaine and adrenaline solutions for extradural infusion.

Fentanyl and bupivacaine were tested for their stability when diluted with 0.9% sodium chloride to 4 micrograms ml-1 and 0.1% respectively, in 100-ml polyvinyl chloride (PVC) bags, alone and in combination, with and without adrenaline 1:200,000. Changes in drug concentration and pH were investigated for 56 days. The combination of fentanyl, bupivacaine and adrenaline was tested under varying environmental conditions of 35 degrees C, 4 degrees C, -18 degrees C, room temperature, darkness and after autoclaving. Fentanyl and bupivacaine were adsorbed onto PVC, resulting in reductions of 12.6% and 9.6% drug mass, respectively, at day 3, but remained stable thereafter. Adrenaline was progressively degraded to a maximum reduction of 37.3% at 35 degrees C by day 56. Solutions containing adrenaline became more acidic over 56 days. Fentanyl and bupivacaine were stable.

Anesthesia, Epidural↗
PubMed1991

Determinants of the reversal time of competitive neuromuscular block by anticholinesterases.

We have assessed, in 200 patients, the determinants of the reversal time of competitive neuromuscular block by anticholinesterase when alcuronium and atracurium neuromuscular block were antagonized by neostigmine 0.04 and 0.08 mg kg-1 and edrophonium 0.5 and 1.0 mg kg-1. A biexponential relationship was found between the reversal time (time from injection of anticholinesterase to a train-of-four ratio of 70%) and the degree of neuromuscular block at reversal (all groups; F ratio, P less than 0.05). Reversal time was determined by two processes: direct antagonism by the anticholinesterase and spontaneous recovery of the neuromuscular blocking agent, with the latter becoming the major determinant at profound levels of neuromuscular block (0-10% of control twitch height). Neostigmine, in the doses studied, appeared to have a higher "ceiling" of neuromuscular block which it completely antagonized, although edrophonium had a more rapid onset of action. The reversal time for alcuronium became progressively longer relative to atracurium as neuromuscular block increased because of the slower spontaneous recovery rate. Avoidance of profound neuromuscular block at the completion of surgery is required to ensure reliable antagonism of the block within 5-10 min by an anticholinesterase. Neostigmine 0.08 mg kg-1 was found to be the most effective agent in antagonizing profound neuromuscular block.

Adult↗
PubMed1990

Pharmacokinetics of atracurium during continuous infusion.

The pharmacokinetics of atracurium were investigated by a model-independent method during continuous infusion under propofol anaesthesia. Following an intubating dose of suxamethonium, atracurium was infused according to a predetermined profile which continually set the infusion rate to maintain stable muscle paralysis and a target steady state plasma concentration when equilibrium between the biophase and plasma had occurred. Atracurium was infused for the first 1 h to maintain a target steady state plasma concentration of 1.0 microgram ml-1. Thereafter, the target plasma concentration was adjusted to maintain 90% muscle paralysis. The maintenance infusion rate required to maintain 90% paralysis was 4.25 (SD) 1.11 micrograms kg-1 min-1, with an estimated steady state plasma concentration of atracurium required to maintain 90% paralysis (Cpss90) of 1.13 (0.24) microgram ml-1. The clearances of atracurium, estimated by the constant infusion rate required to maintain the steady state plasma concentration, at 50-60 min and during estimation of Cpss90 were 3.8 (1.0) and 3.9 (1.1) ml kg-1 min-1 (ns), respectively. The volume of distribution at steady state of atracurium after 1 h of infusion, calculated using the clearance and the area under the plasma concentration-time curve to 1 h, was 130 (50) ml kg-1. These estimates of the pharmacokinetic parameters of atracurium are markedly different from those derived from pharmacokinetic analysis of single bolus dose data. Normalization of the pharmacokinetic parameter estimates by lean body mass decreased interpatient variability and improved precision in comparison with the un-weighted data and normalization by total body weight.

Anesthesia, Intravenous↗
PubMed1990

Pharmacodynamics of atracurium during propofol, thiopentone and opioid anaesthesia.

We have assessed in 20 patients the accuracy and precision of an infusion profile for atracurium, which continually set the infusion rate to maintain stable muscle paralysis and a target steady state plasma concentration, when equilibrium between the biophase and plasma had occurred. Muscle paralysis was stable after 20 min, with a mean absolute drift in muscle paralysis in the succeeding 40 min of 0.13 (SD 0.07)% T1/Tc (height of first twitch/height of control twitch) per min. The plasma samples after 30 min, which were assessed empirically as being in equilibrium with the biophase, had an overall mean bias of 8.0 (SEM 3.7)% (P less than 0.05) and an overall mean absolute prediction error of 16.4 (SEM 2.5)% from the target steady state concentration being delivered by the infusion. The profile was then used to estimate the steady state plasma concentration of atracurium required to maintain 90% paralysis (Cpss90), by manually adjusting the delivered target concentration of the infusion until muscle paralysis was stable at 88-92% inhibition of T1/Tc for 15-20 min, with three plasma samples taken over the next 10 min. Measurements were completed within 60-90 min. The mean Cpss90 of atracurium with propofol was 1.039 (SD 0.224) microgram ml-1 (n = 10), with thiopentone 1.334 (0.378) microgram ml-1 (n = 10), and with opioid anaesthesia 0.915 (0.221) microgram ml-1 (n = 10). These differences in the Cpss90 explain some of the variability in response which occurs with neuromuscular blocking drugs. The technique enables the Cpss90 of a myoneural blocker to be determined by a simple model-independent method.

Adult↗
PubMed1990

Accurate monitoring of neuromuscular blockade using a peripheral nerve stimulator--a review.

For normal anaesthetic practice, monitoring of neuromuscular blockade is best performed by stimulation of the ulnar nerve at the wrist with a peripheral nerve stimulator and evaluation of the response of the thumb. Determination of the initial threshold for stimulation in the awake patient to allow estimation of the current required for supramaximal stimulation is an important set-up procedure to improve accuracy. The degree of paralysis of specific muscle groups such as the diaphragm can be inferred from their sensitivity to neuromuscular blocking agents relative to adductor pollicis. Monitoring with different stimulation patterns allows a wide spectrum of muscle paralyses to be evaluated.

Electric Stimulation↗
PubMed1989

Production of laudanosine following infusion of atracurium in man and its effects on awakening.

Twenty patients were given maximal doses of atracurium or vecuronium by infusion during surgery. Anaesthesia was maintained with an infusion of thiopentone, nitrous oxide and fentanyl. In patients administered atracurium, the plasma laudanosine concentration at cessation of surgery was 0.34 (SD 0.22) micrograms ml-1; there was little tendency to cumulate during operation. A 20% higher arterial concentration of thiopentone was found at awakening in patients given atracurium, suggesting CNS stimulation by laudanosine, although the effect is too modest to be of clinical significance.

Anesthesia Recovery Period↗
PubMed1988

The effects of cardiopulmonary bypass on plasma concentrations and protein binding of methohexital and thiopental.

The effects of cardiopulmonary bypass (CPB) on plasma concentrations and protein binding of methohexital and thiopental were studied during continuous infusions in two groups of ten cardiac surgical patients. Patients were administered an infusion regimen designed to produce a stable total plasma concentration at 5 mg/L for methohexital and 10 mg/L for thiopental. Prior to the commencement of CPB the mean (+/-SD) total plasma methohexital concentration was 5.00 +/- 0.69 mg/L. This fell to 3.12 +/- 0.89 mg/L at two minutes after commencement of CPB, and rose to 4.67 +/- 1.11 mg/L by 75 minutes after commencement of CPB. The unbound fraction rose from 27.1 +/- 5.1% to 42.8 +/- 9.2% at five minutes after the start of CPB, and gradually decreased to 32.1 +/- 4.9% by 75 minutes. The unbound concentration (1.37 +/- 0.32 mg/L) was unaffected by the onset of CPB, being 1.51 +/- 0.49 mg/L at 75 minutes after the start of CPB. Thiopental followed a similar pattern to methohexital, with the total plasma thiopental concentration falling from 9.22 +/- 0.73 mg/L to 4.90 +/- 0.83 mg/L at two minutes after commencement of CPB, and rising again to 7.13 +/- 1.03 mg/L 75 minutes later. During the same period the unbound fraction of thiopental rose from 16.1 +/- 2.5% to 30.3 +/- 7.3% five minutes after the start of CPB, and fell gradually to 22.8 +/- 5.8% after 75 minutes. The unbound concentration (1.51 +/- 0.21 mg/L) was again unchanged by the onset of CPB, being 1.71 +/- 0.29 mg/L at 75 minutes. Plasma protein binding of both drugs correlated strongly with plasma albumin concentration, which decreased by 40% during CPB. It is concluded that hemodilution caused the reduction in total drug concentration and protein binding at the onset of CPB, but that the decrease in protein binding counteracted the dilution of unbound drug, resulting in a stable unbound concentration throughout CPB, and that this effect may be common for barbiturates.

Analysis of Variance↗
PubMed1988

Adverse reactions to atracurium and alcuronium. A prospective surveillance study.

A multicentre prospective surveillance study was undertaken to compare the incidence and severity of adverse reactions attributed to atracurium and alcuronium. Clinical manifestations were used by the anaesthetist to diagnose an adverse reaction (a cutaneous reaction, a greater than 20% change in arterial pressure or heart rate, and bronchospasm). Of the 1956 patients receiving atracurium, 10.1% had adverse reactions compared with 17.9% of the 1425 patients receiving alcuronium (P less than 0.001). There were no longterm sequelae. The atracurium group had a markedly lower incidence of hypotension (3.4% v. 13.7%; P less than 0.0001), but a higher incidence of cutaneous reactions (4.6% v. 2.3%; P less than 0.005) which were not associated with other adverse reactions. There was a low incidence of bronchospasm in both groups (0.2% v. 0.1%).

Adult↗
PubMed1987

Plasma drug efflux--a new approach to optimization of drug infusion for constant blood concentration of thiopental and methohexital.

Plasma Drug Efflux is a time-varying measure of the rate of loss of drug from the plasma during conditions of constant plasma concentration. Its practical use is to define the parameters required for a programmed infusion to maintain a desired plasma concentration. The method of deriving the Efflux function, which does not depend on conventional pharmacokinetic models, was developed and tested using thiopental and methohexital in a total of 51 unselected surgical patients free of hepatic or renal disease. Throughout a predetermined, known, but arbitrary computer-controlled drug infusion, the rate of which was modified according to patient lean body mass (LBM) and the desired concentration, blood samples were taken and the plasma assayed for either drug by an HPLC method. By dividing the known variable infusion rate at the time of each sampling by the arterial plasma concentration at each time, an estimate of the rate of loss of drug from the plasma at each point, the Plasma Drug Efflux, was obtained. An error correcting iterative process was used with successive groups of patients until the optimum infusion profile was achieved. Only three iteration steps were required to optimize the infusion profile for each drug. The optimized infusion profile for thiopental was 25.35e-.145t + 4.85e-.0148t + 8.8 ml X min-1 X kgLBM-1, and, for methohexital, 22.21e-.092t + 5.09e-.0121t + 15 ml X min-1 X kgLBM-1. It was concluded that the process of optimization under clinical conditions resulted in infusion profiles suitable for establishing and maintaining a designated arterial plasma concentration in adult surgical patients for periods up to 3 h.

Adult↗
PubMedDate not supplied

Lidocaine does not depress reflex dilation of the pupil.

BACKGROUND AND OBJECTIVES: Pupillary dilation in response to dermatomal electrical stimulation is one method of determining sensory block level during combined epidural and general anesthesia. Use of this technique may, however, be confounded by systemic absorption of epidurally administered local anesthetics. Accordingly, the effects of intravenous lidocaine on the magnitude and duration of reflex pupillary dilation were evaluated. METHODS: Six volunteers were each anesthetized twice with desflurane 3.5-6.0%. During one anesthetic, intravenous lidocaine was administered to a plasma concentration of 5.3 +/- 1.5 micrograms/mL. When the plasma concentrations were stable, a 5-second tetanic electrical stimulus was applied. Pupil size was then recorded for 8 minutes. RESULTS: Lidocaine, at plasma concentrations near 5 micrograms/mL, did not significantly alter the pupillary response to electrical stimulation. In contrast, stimulus-induced increase in heart rate was obliterated. Painful stimulation did not increase systolic blood pressure in either case. CONCLUSIONS: Typical plasma lidocaine concentrations observed during epidural anesthesia are unlikely to prevent the use of pupillary responses to evaluate sensory block level.

Adult↗
PubMedDate not supplied

Effect of amlodipine on cardiopulmonary performance in volunteers.

1. In order to exclude a significant effect of the calcium channel antagonist amlodipine on cardiopulmonary performance in normal subjects, we performed a double-blind cross-over study of amlodipine (10 mg daily for 2 weeks) on oxygen uptake and catecholamine responses during exercise in eight volunteers. 2. Despite a therapeutic plasma concentration of amlodipine (22.8+/-9 ng/mL), there was no change in resting heart rate or blood pressure. Amlodipine did not cause significant change in oxygen uptake at the anaerobic threshold or at maximum exercise and there was also no change in heart rate or catecholamine responses. 3. Although there was an awareness of peripheral vasodilation and reports of lethargy during the active treatment period, the volunteers had no objective evidence of a decrease in cardiopulmonary performance. We suggest that use of amlodipine as a vasodilator in the perioperative period would not add to the myocardial depressant effects of general anaesthesia in patients with normal cardiac function.

Adult↗