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Biomedical subjects

R L Knill

Publications and source records attributed to R L Knill.

At least 37 records · Page 2Linked to original sources
PubMed1986

Ventilatory compensation for continuous inspiratory resistive and elastic loads during halothane anesthesia in humans.

Inspiratory mechanical loads were applied to the airway continuously for 5 min in healthy young adult volunteers maintained in a near steady-state of halothane anesthesia 1.1 MAC. The loads, both flow resistive and elastic in nature, had been selected to reduce the first loaded tidal volume approximately 10, 30 or 50%--these being designated "small," "medium," and "large" loads, respectively. The actual magnitudes of resistive load were 8 +/- 1, 21 +/- 3, and 48 +/- 6 cmH2O X l-1 X s, and of elastic load 6 +/- 1, 18 +/- 1, and 41 +/- 5 cmH2O X l-1 (mean +/- SEM). All loads caused an immediate reduction of ventilation proportional to the size of the load. This was followed by a gradual recovery of ventilation toward control values over approximately 2 min and then nearly stable ventilation for the rest of the loading period. Respiratory frequency was unchanged throughout. At 5 min of loading, ventilation and PaCO2 had been nearly steady for 3 min and O2 uptake and CO2 output at the airway were unchanged from control, suggesting the establishment of a near steady respiratory state. With the small and medium loads of both types, ventilation and PaCO2 in this near steady-state were not detectably different from control. With the large loads, however, ventilation was significantly reduced and PaCO2 slightly increased. The end-expiratory position of the chest wall and the relative contributions of the rib cage and abdomen-diaphragm to ventilation, as estimated by anteroposterior chest wall magnetometers, were not consistently altered by any load.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMed1985

Evaluation of arterial oxygenation during anaesthesia.

The clinical or physiological signs of hypoxaemia have limited value during anaesthesia. In the absence of surgical bleeding, the best signs are probably cyanosis and/or bradycardia-although neither is sensitive or specific. A moderate degree of hypoxaemia can be present without clinical signs! In the presence of surgical bleeding, the best sign may be darkening of fresh blood in the surgical field. The only reliable indicators of arterial oxygenation available for routine anaesthesia are the laboratory measurements of PaO2 and SaO2. Unfortunately, these measurements are intermittent and delayed. The modern Hewlett Packard and Biox ear oximeters can provide an immediate and continuous estimate of arterial oxygen saturation in anaesthetized humans. These instruments are extremely useful in clinical practice when the risks of hypoxaemia or hypoxaemic injury are high. Unfortunately, cost precludes their general use. The safety of anaesthesia would no doubt be improved with an inexpensive reliable monitor of arterial oxygenation.

Anesthesia, General↗
PubMed1985

Ventilatory responses to acute metabolic acidemia in humans awake, sedated, and anesthetized with halothane.

The authors produced metabolic acidemia acutely in human subjects awake, sedated with halothane (0.1 MAC), and anesthetized with halothane (1.0 MAC) by infusing L-arginine hydrochloride, 5-6 mmol X kg-1, over 3 h. Ventilation was recorded at resting arterial hydrogen ion concentration [( H+]a) and at 2-4 isocapnic increments of [H+]a, in each case, while end-tidal oxygen tension (PETO2) was varied between greater than 300 mmHg and 45 mmHg. Total increments of [H+]a in awake, sedated, and anesthetized subjects were 13 +/- 4, 12 +/- 2, and 12 +/- 3 nmol X 1(-1) (means +/- SD). In the awake state, metabolic acidemia increased ventilation (VI) in proportion to [H+]a. The magnitude of response increased with reduced PETO2, such that the response to acidemia and hypoxemia combined was synergistic. The delta VI/delta [H+]a slopes at PETO2 values of greater than 300, 100-120, and 45 mmHg were 0.47 +/- 0.27, 0.85 +/- 0.24, and 3.01 +/- 1.30 1 X min-1 X nmol-1 X 1, respectively (means +/- SD). Halothane sedation reduced the responses to added [H+]a determined at PETO2 values of 100-120 and 45 mmHg, as well as the response to hypoxemia and to the interaction of acidemia and hypoxemia, each to less than half awake values. Halothane anesthesia further impaired the responses to [H+]a and virtually abolished the response to hypoxemia and to acidemia-hypoxemia interaction. A small residual response to added [H+]a during anesthesia could be accounted for by a slight concurrent increase of PaCO2, leaving no response attributable to metabolic [H+]a itself.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1984

Site of selective action of halothane on the peripheral chemoreflex pathway in humans.

Halothane in humans depresses the ventilatory response to hypoxemia in a manner that suggests a selective action on one or more components of the peripheral chemoreflex arc. To test the hypothesis that this action is at the carotid bodies themselves, the authors studied the ventilatory response to subanesthetic concentrations of halothane (0.15-0.30% inspired) in six fit volunteers maintained in a steady state of isocapnic hypoxemia (PEO2 50 mmHg). Upon exposure to halothane, hypoxemia-driven ventilation decreased promptly and progressively (from 7.5 +/- 1.2 1 X min-1 X m-2 in the control state to 5.9 +/- 0.9 and 4.8 +/- 0.7 1 X min-1 X m-2 at 30 s and 60 s of inhalation respectively, means +/- SEM). The relationship of hypoxemia-driven ventilation to end-tidal halothane tensions at 30 and 60 s of halothane wash-in (PEHal 0.4 and 0.6 mmHg, respectively) approached the relationship observed in near steady states of halothane inhalation. The results are interpreted as indicating that the site of selective action is at a tissue that accumulates halothane very rapidly during the first minute of inhalation. To make possible such pharmacokinetics, that tissue would require a location having a brief circulatory transit time from the lungs, and an extremely high rate of perfusion in relation to its capacity for uptake of halothane. The only tissue of the peripheral chemoreflex pathway that can satisfy these requirements is that of the carotid bodies.

Adult↗
PubMed1983

Diazepam sedation reduces functional residual capacity and alters the distribution of ventilation in man.

We measured ventilation and static lung volumes in five fit volunteers in the right lateral decubitus position, while they were fully awake and while sedated with diazepam. We also assessed the distributions of ventilation and perfusion in the lungs, using inhalations and intravenous injections of xenon-127. Diazepam, 0.04 mg . kg-1, was administered every three to five minutes as required to induce and maintain a state of sedation which was moderately heavy. Total doses ranged from 0.16 to 0.38 mg . kg-1. Sedation did not alter minute ventilation, but reduced tidal volume, increased breathing frequency and reduced functional residual capacity slightly. Sedation also diminished the normal gradient of ventilation from non-dependent to dependent regions of the lungs. Spontaneous episodes of very small tidal volume breathing during sedation were associated with a marked reduction or cessation of ventilation of the most dependent region of the lungs. There were no sedation-related changes in the distribution of perfusion. These effects of moderately heavy sedation may contribute to the hypoxaemia and impairment of pulmonary gas exchange often present during recovery from general anaesthesia.

Adult↗
PubMed1983

Blood solubility of isoflurane measured by a multiple gas phase equilibration technique.

Using a multiple gas phase equilibration technique, we determined the solubility of isoflurane in arterial blood at 37 degrees C obtained from patients anaesthetized with isoflurane. Goodness of fit of individual sets of data to a predicted decline of isoflurane concentration in successive equilibrated gas phases and reproducibility of results indicate that the analytical technique was acceptably accurate. In blood samples taken from twenty-three patients undergoing minor surgical procedures, the blood/gas partition coefficient of isoflurane was 1.20 +/- 0.08 (mean +/- S.D.). Individual values were not detectably related to absolute tension of isoflurane, preoperative haemoglobin concentration nor patient age. In samples taken from twenty neurosurgical patients, the blood/gas partition coefficient was slightly less, 1.14 +/- 0.09 (p less than 0.05), a difference we attribute to the effect of previously infused mannitol. In vitro, blood solubility of isoflurane was decreased by haemodilution with normal saline, mannitol 20 per cent or plasma, was increased by hypothermia (30 degrees C) and was decreased by hyperthermia (40 degrees C). We conclude that the solubility of isoflurane in human blood is approximately half that of halothane.

Adult↗
PubMed1983

Chemical regulation of ventilation during isoflurane sedation and anaesthesia in humans.

To assess the effects of isoflurane on chemical regulation of ventilation, we studied the ventilatory responses to (1) hyperoxic hypercarbia, (2) isocapnic hypoxaemia, and (3) a single half vital capacity breath of carbon dioxide 20 per cent in oxygen in 12 human subjects, awake and sedated or anaesthetized with isoflurane, 0.1 or 1.1 MAC. Sedation did not alter ventilation nor the ventilatory response to hypercarbia but reduced the responses to hypoxaemia and to the half vital capacity breath of CO2. Anaesthesia reduced ventilation and the response to hypercarbia and nearly abolished the responses to hypoxaemia and to the breath of CO2. The results indicate that isoflurane reduces ventilatory responses to several chemical drives and that it selectively impairs those responses mediated by peripheral chemoreceptors. In these respects, isoflurane is similar to halothane and enflurane.

Adult↗
PubMed1982

Variable effects of anaesthetics on the ventilatory response to hypoxaemia in man.

We compared the ventilatory response to isocapnic hypoxaemia with a standard response to hyperoxic hypercarbia in human subjects sedated with methoxyflurane, diethyl ether or nitrous oxide, or anaesthetized with methoxyflurane. Compared to the awake state, methoxyflurane 0.1 MAC sedation did not alter either response significantly; methoxyflurane 1.1 MAC anaesthesia depressed both, with a somewhat greater effect on the hypoxaemic response. Diethyl ether 0.1 MAC sedation reduced only the hypoxaemic response. Nitrous oxide 0.1 MAC reduced both hypoxaemic and carbon dioxide responses in parallel. The evidence suggests that all three agents - like thiopentone, halothane and enflurane - can impair the ventilatory response to isocapnic hypoxaemia in man, but that in relation to the carbon dioxide responses, the magnitude of this depressive effect varies. Halothane and enflurane are the most depressant, nitrous oxide and thiopentone the least, with methoxyflurane and diethyl ether appearing to be intermediate in effect.

Adult↗
PubMed1982

Respiratory effects of nitrous during enflurane anesthesia in humans.

The authors measured resting ventilation, the ventilatory response to added CO2, the VD/VT ratio, the rate of carbon dioxide output, and arterial PCO2 in four healthy volunteers, awake and anesthetized with, in order (I) enflurane 0.4 MAC with nitrous oxide 70 per cent, (II) enflurane 1.1 MAC with nitrous oxide 70 per cent, and (III) enflurane 1.1 MAC alone. Enflurane 1.1 MAC reduced ventilation and the response to added CO2 markedly, increased the VD/VT radio, reduced rate of CO2 output, and elevated values of PaCO2 from 41 +/- 1 to 65 +/- 3 mmHg (mean +/- SEM). Enflurane 1.1 MAC with nitrous oxide 70 per cent had similar effects. Enflurane 1.1 MAC with nitrous oxide 70 per cent had similar effects. Enflurane 0.4 MAC with nitrous oxide 70 per cent caused much smaller changes in each measured respiratory variable, increasing PaCO2 values to only 49 +/- 1 mmHg. The results indicate that enflurane 1.1 MAC alone is too potent a depressant of alveolar ventilation to permit spontaneous breathing, but that the "equi-anesthetic" enflurane 0.4 MAC with nitrous oxide 70 per cent may not be. The magnitude of the beneficial respiratory effects of substituting nitrous oxide for an equivalent amount of vapor is substantially greater with enflurane than with either halothane or isoflurane.

Adult↗
PubMed1982

Assessment of two noninvasive monitors of arterial oxygenation in anesthetized man.

The Hewlett-Packard 47201A ear oximeter and the Radiometer TCM1 transcutaneous oxygen monitor were evaluated for use as noninvasive monitors of arterial oxygenation during inhalational anesthesia in man. Thirty-four healthy adult volunteers were anesthetized to steady states with halothane, enflurane, or isoflurane, and were studied either before or during surgery. Oxygen levels were varied over ranges that included hypoxemia, by manipulating FIO2. Oximeter estimates of SaO2 values and transcutaneous estimates of PaO2 values were compared with conventional measurements of each. Oximeter readings responded rapidly to changes of inspired oxygen concentration and were acceptably accurate estimates of SaO2, except at lower SaO2 levels (less than 80%) during anesthesia without surgery. Transcutaneous oxygen tension readings responded relatively slowly to changes of FIO2 and were frequently inaccurate reflections of PaO2 values. We consider this oximeter suitable as a monitor of arterial oxygenation during anesthesia, but find the transcutaneous electrode unsatisfactory.

Adult↗
PubMed1981

Lumbar epidural morphine as an effective analgesic following cholecystectomy.

Relief of pain with epidural morphine was evaluated in five patient subjects during two consecutive twenty-four periods after cholecystectomy. In one period, each subject received lumbar epidural morphine, first 4-6mg, and twelve hours later, 2-3 mg; in the other period, epidural placebo at the same times. Except for four hours before each injection and twenty minutes thereafter, intramuscular morphine was administered as required throughout. The experiments were double-blind. Epidural morphine, unlike epidural placebo, reduced both a visual pain analogue score (p less than 0.05) and a pain questionnaire score (p less than 0.01) twenty minutes after injection. Epidural morphine compared to placebo reduced by one-half the total amount of narcotic (epidural plus intramuscular) administered over the twenty-four hour period (p less than 0.05). Four of five subjects clearly preferred analgesia with epidural morphine over the effect of placebo plus therapeutic doses of intramuscular morphine. We conclude that epidural morphine, administered in this manner, is effective in relieving pain after cholecystectomy and that it may be preferred by patients over conventional intramuscular morphine.

Adult↗
PubMed1981

Regional analgesic effect of epidural morphine in volunteers.

Limb ischaemia induced by a sub-maximum effort tourniquet technique was used to characterize the analgesic effects of lumbar epidural morphine in volunteers. As an index of pain threshold, we measured the time to perception of pain in and upper an a lower limb before and at intervals up to six hours following epidural injections of morphine 3.5 mg an 7.0 mg, and before and after subcutaneous injections of the same doses. Subcutaneous morphine had no significant effect on the times to perception of pain in either limb. Lumbar epidural morphine did not alter upper limb times, but markedly delayed the onset of pain in the lower limbs. This lower limb analgesic effect was apparent thirty minutes after injection, peaked at about ninety minutes and was still present after six hours. Serum levels of morphine were nearly identical after subcutaneous and epidural injections of the same dose. We conclude that lumbar epidural morphine produces marked analgesia for this type of experimental pain primarily by a "regional" effect rather than as a result of systemic absorption. This regional effect develops slowly and is prolonged.

Analgesics↗
PubMed1981

Epidural morphine causes delayed and prolonged ventilatory depression.

We measured ventilation, PETCO2 and the Ventilatory response to added carbon dioxide before and at intervals up to six hours after epidural morphine 3.5 mg and 7.0 mg, and before and after subcutaneous injections of the same dose in volunteers. Subcutaneous morphine increased PETCO2 slightly, but did not alter the sensitivity of the response to added carbon dioxide. Epidural morphine reduced ventilation and increased PETCO2 progressively with time and, six hours after injection, reduced the ventilatory response to carbon dioxide considerably. In two subjects tested, these ventilatory effects persisted for twenty-four hours. The added effects of epidural morphine were due primarily to reductions in tidal volume and the tidal volume response to added carbon dioxide. We conclude that epidural morphine causes delayed and very prolonged ventilatory depression, which is of a greater magnitude and a different ventilatory pattern than that which follows the same does of morphine given subcutaneously. Ventilatory depression after lumbar epidural morphine develops slowly, as the lower limb analgesic effect is waning.

Adult↗