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Biomedical subjects

D R Morel

Publications and source records attributed to D R Morel.

At least 91 records · Page 5Linked to original sources
PubMed1989

[Post-traumatic pulmonary insufficiency: therapeutic measures].

The pathophysiology of posttraumatic pulmonary failure is today reasonably well known. Interaction of altered granulocytes with the pulmonary parenchyma in the form of an inflammatory reaction plays an important role. Gas exchange failure can be a major problem in these patients and influence the prognosis. No effective preventive treatment is known at present except for rapid and appropriate surgical management together with an adequate fluid resuscitation. In addition, the risk of infection and sepsis must be reduced as far as possible and dysfunction of other organ systems prevented if the prognosis is to be improved. Administration of anti-inflammatory agents and corticosteroids has been shown to be without beneficial effect and dangerous in this situation. Intubation and ventilatory assistance should be used depending on respiratory status and pulmonary gas exchange, although potentially lifethreatening side effects of this treatment must be considered. Continuous specific monitoring of respiratory function must be started in the patient after multiple trauma to follow the course of pulmonary dysfunction and adapt therapy.

Granulocytes↗
PubMed1989

Pipecuronium-induced neuromuscular blockade during nitrous oxide-fentanyl, isoflurane, and halothane anesthesia in adults and children.

To determine in adults and children the dose-response relationship and the duration of action of pipecuronium bromide during fentanyl-nitrous oxide (N2O), isoflurane, and halothane anesthesia, the authors studied 30 ASA Physical Status 1-2 adults (age: 16-55 yr) and 30 ASA Physical Status 1-2 children (age: 1.7-11.5 yr) during minor elective surgery. Patients were anesthetized with N2O/O2 (60:40) supplemented with either fentanyl (4 micrograms/kg), or isoflurane (adults, 0.9%; children, 1.2%), or halothane (adults, 0.6%; children, 0.7%). Neuromuscular (NM) blockade was measured by electromyography. Incremental iv doses of pipecuronium were administered to determine the cumulative dose-response relationship of pipecuronium until a 95% twitch depression (ED95) had been obtained. In adults, ED50 was 31.7 +/- 2.9 micrograms/kg (mean +/- SE) during fentanyl-N2O/O2, reduced by isoflurane (18.0 +/- 4.8 micrograms/kg, P less than 0.05) but not by halothane (25.0 +/- 2.6 micrograms/kg, NS). ED95 was 59.4 +/- 5.4 micrograms/kg during fentanyl-N2O/O2, reduced by isoflurane (42.3 +/- 2.5 micrograms/kg, P less than 0.05), but not by halothane (49.7 +/- 3.1 micrograms/kg, NS). In children, ED50 was 43.9 +/- 4.7 micrograms/kg during fentanyl-N2O/O2, reduced by isoflurane (23.1 +/- 1.6 micrograms/kg, P less than 0.05), and halothane (33.2 +/- 3.2 micrograms/kg, P less than 0.05). ED95 was 79.3 +/- 9.8 micrograms/kg during fentanyl-N2O/O2, and reduced by isoflurane (49.1 +/- 3.1 micrograms/kg, P less than 0.05), but not by halothane (62.5 +/- 7.3 micrograms/kg, NS). Comparison between adults and children reveals no statistically significant differences, except for ED50 during fentanyl-N2O/O2 anesthesia which was increased in children.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Effect of the knee-chest position on cerebral blood flow in patients undergoing lumbar spinal surgery.

The cerebral haemodynamic effect of the knee-chest position was evaluated in 15 anaesthetised patients undergoing elective lumbar disc surgery and divided into a control group (n = 8) where cerebral blood flow (CBF) was measured twice in the supine position and an experimental group (n = 7) where the first CBF was measured in the supine position and the second in the knee-chest position. CBF was measured by a modified intravenous 133xenon washout technique. Mean global CBF did not change in control group (56.1, SD 9.2 versus 52.8, SD 10.8 units) and was not significantly modified by the knee-chest posture, 51.8, SD 8.8 units versus 53.9, SD 7.4 units in the supine position. The results indicate that mean global CBF in the knee-chest position is not different from CBF in the supine position in healthy patients.

Adult↗
PubMed1988

Lung uptake of 131I-metaiodobenzylguanidine in sheep. An in vivo measurement of pulmonary metabolic function.

Circulating biogenic amines are known to be cleared by the mammalian lung. Their lung uptake is considered as an indicator of pulmonary endothelial integrity. Unfortunately, their use as markers of pulmonary metabolic function in human pathology is precluded by their biological effects and by the type of radiolabeling (3H and 14C), making them harmful for repeat injections and unfit for scintigraphy. Metaiodobenzylguanidine (MIBG) is structurally related to the neuron blocking agent guanethidine, devoid of significant biological effects, and has been shown to be extracted by the same active sodium dependent, saturable transport as norepinephrine in perfused rat lungs in vitro. We studied the single pass lung extraction of 131I-MIBG in five awake and five anaesthetised sheep using the standard double indicator dilution technique with 99mTc-human serum albumin (HSA) as an intravascular reference tracer. Intravenous bolus injection of increasing doses of MIBG up to 400 nmol resulted in a significant (F ratio = 7.778, P less than 0.0001) dose dependent decrease of MIBG extraction in both awake and anaesthetised sheep, without significant differences of extraction values between the two groups. For the 10 sheep, the averaged percentage single pass pulmonary uptake of MIBG at the peak of the dilution curve decreased from 32% +/- 3% (mean +/- SE, n = 27 measurements) with 20 nmol to 18% +/- 2% (n = 32) with 400 nmol. Estimates of the apparent Michaelis-Menten constant (Km) averaged 2 +/- 1.2 microM (n = 7), whereas estimates of the apparent maximum velocity of removal (Vmax) was 1.1 +/- 0.5 mumol/min (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗
PubMed1988

A new imaging approach to quantitative evaluation of pulmonary vascular endothelial metabolism.

There has been no noninvasive, readily available method for clinically evaluating changes in pulmonary metabolism of biogenic aminelike substances. Such metabolic changes, which almost surely take place on the surface or within the endothelial cells that line the pulmonary vasculature, are likely to be significant components of the overall clinical response of the lung to many disorders. Radioiodinated metaiodobenzylguanidine (MIBG) shows properties in isolated, perfused lung preparations that simulate those of biogenic amines (eg, its uptake is sodium-dependent and virtually abolished by ouabain). New data from studies in sheep and humans indicate that changes in first transit pulmonary extraction of this compound can easily be monitored externally using conventional gamma camera-computer systems. MIBG labeled with iodine 123 may provide an important new means for clinical assessment of changes in pulmonary endothelial metabolism.

3-Iodobenzylguanidine↗
PubMed1988

Acute pulmonary vasoconstriction and thromboxane release during protamine reversal of heparin anticoagulation in awake sheep. Evidence for the role of reactive oxygen metabolites following nonimmunological complement activation.

When protamine (2 mg/kg) was injected intravenously into awake sheep 5 minutes after infusing heparin (200 units/kg), there was transient diffuse pulmonary vasoconstriction with mean pulmonary arterial pressure increasing from 18.0 +/- 0.7 to 43.8 +/- 2.7 mm Hg at 1 minute (x +/- SEM; n = 10). In addition, there was profound leukopenia (36.9 +/- 7.7% of baseline values at 2 minutes) with transpulmonary leukocyte sequestration and transiently elevated plasma concentrations of C3a (from 420 +/- 146 to 1,599 +/- 249 ng/ml; n = 3, p less than 0.01) and thromboxane B2 (from 0.30 +/- 0.05 to 6.3 +/- 2.8 ng/ml; n = 10, p less than 0.0001), without significant increases of plasma 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha, leukotrienes, or histamine. Intravenous injection of protamine alone produced no hemodynamic effects and did not increase plasma levels of vasoconstrictor eicosanoids. Intravenous pretreatment with either a cyclooxygenase inhibitor or a hydrogen peroxide scavenger (dimethylthiourea) blocked both the increases of thromboxane levels and the pulmonary vasoconstriction.

Animals↗
PubMed1987

Dose-dependent effects of a pyridoquinazoline thromboxane synthetase inhibitor on arachidonic acid metabolites and hemodynamics during E. coli endotoxemia in anesthetized sheep.

We investigated the effects of a new pyridoquinazoline thromboxane synthetase inhibitor infused before administering Escherichia Coli endotoxin into 18 anesthetized sheep with lung lymph fistulas. In normal sheep increasing plasma Ro 23-3423 concentrations were associated with increased plasma levels of 6-keto-PGF1 alpha, a reduced systemic vascular resistance (SVR, r = -0.80) and systemic arterial pressure (SAP, r = -0.92), the mean SAP falling from 80 to 50 mm Hg at the 20 and 30 mg/kg doses. Endotoxin infused into normal sheep caused transient pulmonary vasoconstriction associated with increased TxB2 and 6-keto-PGF1 alpha levels while vasoconstriction and TxB2 increase were significantly inhibited by pretreatment with Ro 23-3423 in a dose-dependent manner. When compared to controls, plasma and lymph levels of 6-keto-PGF1 alpha, PGF2 alpha and PGE2 after endotoxin infusion were increased several-fold by administering Ro 23-3423 up to plasma levels of 10 micrograms/ml. Doses over 30 mg/kg with blood levels above 10 micrograms/ml reduced plasma and lymph levels of 6-keto-PGF1 alpha, PGF2 alpha and PGE2, suggesting cyclooxygenase blockade at this dose. The peak 6-keto-PGF1 alpha levels at 60 min after endotoxin infusion in sheep with Ro-23-3423 levels below 10 micrograms/ml were associated with the greatest systemic hypotension due to a reduced SVR (r = -0.86). After endotoxin infusion the leukotrienes B4, C4, D4 and E4 in lung lymph were assayed by radioimmunoassay and high pressure liquid chromatography and remained at baseline values.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

C5a and thromboxane generation associated with pulmonary vaso- and broncho-constriction during protamine reversal of heparin.

The authors conducted a study in humans to determine the mediators associated with acute pulmonary vaso- and broncho-constriction occurring episodically with protamine reversal of heparin anticoagulation. Of 48 adult patients investigated prospectively after termination of cardiopulmonary bypass, two presented a sudden increase of airway pressure, acute pulmonary hypertension, and systemic hypotension 1-3 min after right atrial protamine injection. In these two subjects, plasma levels of C5a increased from 0.7 and 2.2 to 9.8 and 9.9 ng/ml, respectively, and thromboxane B2 increased from 0.26 and 0.34 to 7.5 and 16.2 ng/ml 1 minute after drug injection. A third subject not identified prospectively had an identical reaction and mediator profile (C5a, 10.2 ng/ml; TxB2, 18.6 ng/ml at 1 min). The plasma levels of these mediators were unchanged in the remaining patients (C5a, 0.7 +/- 1.1 [x +/- S.D.] to 0.6 +/- 0.9 ng/ml; TxB2, 0.16 +/- 0.12 to 0.15 +/- 0.07 ng/ml). Plasma histamine was not involved in this type of reaction, but increased from 0.7-10.4 ng/ml in a fourth patient who became hypotensive without acute pulmonary hypertension, bronchoconstriction, or elevation of C5a or TxB2. The authors' data indicate that the generation of high plasma levels of C5a anaphylatoxins and thromboxane is associated with pulmonary vaso- and broncho-constriction induced by protamine reversal of heparin in humans.

Adult↗
PubMed1986

Noninvasive evaluation of breathing pattern and thoraco-abdominal motion following the infusion of ketamine or droperidol in humans.

The authors compared the respiratory effects of an intravenous infusion of ketamine (1 mg X kg-1) with droperidol (0.1 mg X kg-1), or placebo on three different occasions in a double-blind, randomized fashion in eight healthy volunteers. Breathing pattern, thoraco-abdominal motion, end-expiratory positions of the rib cage and abdomen, arterial hemoglobin oxygen saturation (SaO2), and end-tidal carbon dioxide concentration (FECO2) were continuously measured with noninvasive techniques. During the 1-h monitoring period following drug injection, droperidol produced occasionally significant but clinically unimportant differences in respiratory variables when compared with placebo. In contrast, ketamine induced a significant (P less than 0.001) and persistent increase in minute ventilation (+75%) from 5 to 20 min after start of infusion by increasing both the driving (i.e., tidal volume/inspiratory time [VT/Ti]) and the timing (i.e., inspiratory time/total respiratory cycle time [Ti/Ttot]) components of ventilation (Milic-Emili J, Grunstein MM: Chest 70 (Suppl): 131-133, 1976). This was obtained without any significant change in end-expiratory positions or change in relative rib cage contribution to tidal volume. Despite multiple apneic episodes observed with ketamine, the subjects maintained a stable SaO2 and FECO2, indicating no resting respiratory depression. This study, performed with a noninvasive respiratory monitoring technique, confirms that droperidol infused over 5 min at a clinically used dosage does not cause respiratory depression in healthy subjects, whereas ketamine produces an important ventilatory stimulation.

Abdomen↗
PubMed1985

Pulmonary extraction of serotonin and propranolol in patients with adult respiratory distress syndrome.

Because injury to the pulmonary vascular endothelium is associated with the development of the adult respiratory distress syndrome (ARDS), we assessed the metabolic function of pulmonary endothelial cells by the measurements of the first-pass pulmonary extraction of [14C]serotonin and [3H]propranolol in 15 patients with ARDS and 15 patients at risk for developing ARDS. Serotonin extraction ratio was lower in patients with ARDS (0.85 +/- 0.10, mean +/- SD) than in patients at risk (0.91 +/- 0.04) (p less than 0.025), and both values were significantly reduced (p less than 0.005) when compared with a control group value (0.97 +/- 0.01). The decrease in serotonin extraction was correlated with the severity of ARDS (r = -0.67) (p less than 0.001) and with pulmonary function changes over time. Propranolol extraction ratio was decreased in patients at risk (0.66 +/- 0.11) (p less than 0.005) but not in patients with ARDS (0.75 +/- 0.11), when compared with those in the control group (0.81 +/- 0.03). Low values in patients at risk were restored to normal by continuous positive airway pressure breathing. We conclude that pulmonary extraction of serotonin, an index of pulmonary endothelial cell function, correlates with the severity of ARDS.

Adult↗
PubMed1984

Evaluation of I.V. labetalol for treatment of posttraumatic hyperdynamic state.

A hyperdynamic state, characterized by an elevated blood pressure and tachycardia is frequently seen during the first few days following severe multiple trauma. We examined the cardiovascular effects of the alpha and beta adrenoceptor blocking agent labetalol in patients presenting a hyperdynamic cardiovascular state some days after major trauma. Ten patients with a heart rate-systolic blood pressure product (RPP) of more than 2000 during 6 consecutive hours, despite normovolaemia, adequate ventilation, analgesia and sedation were investigated. After a mean dose of 2.1 +/- 1.2 mg X kg-1 (mean +/- SD) of labetalol injected intravenously over a 10-min period, heart rate decreased from 117 +/- 28 to 102 +/- 19 beats X min-1, systolic arterial pressure from 25 +/- 3.5 to 18.5 +/- 2.7 kPa, diastolic pressure from 11 +/- 1.7 to 9.5 +/- 1.7 kPa, mean arterial blood pressure from 15.5 +/- 2.1 to 12.4 +/- 2.1 kPa, and the RPP from 2880 +/- 867 to 1853 +/- 373. The beneficial effect of this dose lasted 24 h in 8 of 10 patients without additional administration. No important side effects such as cardiac arrhythmias, hypotension, or bronchospasm were noted. We conclude that labetalol used in fractional intravenous doses permits an adequate treatment of a "hypertension-tachycardia syndrome" in severely injured patients.

Adult↗
PubMed1984

Effect of intravenous midazolam on breathing pattern and chest wall mechanics in human.

Breathing pattern, thoracoabdominal motion, and separate end-expiratory positions of the rib cage and abdomen were measured noninvasively in eight healthy subjects before and after intravenous administration of either placebo or midazolam, a short-acting benzodiazepine. Compared with placebo, midazolam produced a significant (P less than 0.01) decrease in mean inspiratory flow of 29% from preinjection values, resulting in a 39% reduction in tidal volume (VT). This ventilatory depression was partly compensated by a 35% decrease in expiratory time producing an increase in respiratory rate (+39%). The fall in VT was almost entirely (91%) mediated by a reduction of the abdominal contribution to tidal breathing while sparing rib cage motion. This fact contrasts with the effects of inhalational anesthetics or morphine, which preferentially depress rib cage expansion, indicating that thoracoabdominal motion may selectively be depressed by different pharmacological agents. In addition, continuous recording of end-expiratory levels showed a significant transient fall in the rib cage's end-tidal position 2 min after midazolam administration associated with the occurrence of central apneas.

Abdominal Muscles↗
PubMed1983

[Studying pulmonary mechanics in intensive care].

Assessing pulmonary function in critically ill patients is difficult, mainly because of lack of cooperation, artificial ventilation and jeopardized vital functions. We describe bedside methods and mobile equipment used to measure lung volumes, static pulmonary and thoracic compliance. The analysis of single and multiple-breath nitrogen washout curves allows an estimation of closing volume and an assessment of the inhomogeneity of ventilation. The use of a microcomputer facilitates recording, calculation, reproduction and classification of the data; it also permits the collection of more information in a shorter time, allowing the adjustment of mechanical ventilation to the underlying pulmonary disease.

Critical Care↗
PubMed1983

Noninvasive ventilatory monitoring with bellows pneumographs in supine subjects.

We compared simultaneous measurements of ventilatory movements obtained by a bellows pneumograph (BP) and a respiratory inductive plethysmograph (RIP) vs. integrated volume from a pneumotachograph in seven healthy volunteers during different respiratory patterns. The purpose of this study was to assess if a computer-aided calibration procedure could improve the accuracy of BP, a simple semiquantitative method for noninvasive ventilatory monitoring in supine subjects. Both devices were repeatedly calibrated against a pneumotachograph in the same posture with a computer-aided least-squares method. One calibration maneuver was sufficient to achieve a minimal relative difference in volume measurements between the RIP as well as the BP and the pneumotachograph of less than 1.2 +/- 4.5 (SD) %. The accuracy remained in this range during the subsequent calibrations with time (1 h) and after body movements. However, this difference increased significantly with both devices when the subjects were studied in the lateral decubitus position. The present study indicates that despite theoretical advantages of the RIP, the BP, when properly calibrated, has similar performances in supine subjects for monitoring ventilation; it is simpler and less expensive than the RIP and is devoid of electrical drift and artifacts.

Adult↗
PubMed1982

I.v. labetalol in the treatment of hypertension following coronary-artery surgery.

The cardiovascular effects of incremental fixed i.v. doses of labetalol were evaluated in 10 normovolaemic sedated patients presenting with hypertension and tachycardia in the early period after myocardial revascularization. At first dose of 20 mg was sufficient to provoke a significant (P less than 0.01) mean decrease in systolic (-9.3%), diastolic (-8.2%) and mean arterial (-7.9%) pressure (AP) and in the rate-pressure product (RPP) (-13.1%). The mean heart rate (HR) did not change significantly, but a linear correlation could be established between the change at 2 min and the value before injection (r = 0.73). A second dose of labetalol 40 mg given 5 min later did not decrease AP further, but a significant decrease in HR was noted. A marked difference in the individual response among patients was found as the range of effective total doses per kg body weight was 0.6-4.1 mg kg-1 (mean 2.2) Apart from one patient, no patient needed vagolytic or sympathomimetic drugs to oppose the alpha or beta actions of labetalol during the 24-h follow-up period.

Aged↗