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Biomedical subjects

L I Eriksson

Publications and source records attributed to L I Eriksson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Acute quadriplegia and loss of muscle myosin in patients treated with nondepolarizing neuromuscular blocking agents and corticosteroids: mechanisms at the cellular and molecular levels.

OBJECTIVE: Long-term treatment with nondepolarizing neuromuscular blocking agents and corticosteroids in the intensive care unit is not benign, and an increasing number of patients with acute quadriplegic myopathy have been reported with increased use of these drugs. The purpose of this study was to investigate the mechanisms underlying acute quadriplegic myopathy. DESIGN: Percutaneous muscle biopsy samples were obtained, and electrophysiologic examinations were performed during the acute phase and during recovery in patients with acute quadriplegic myopathy. Regulation of muscle contraction and myofibrillar protein synthesis was studied using cell physiologic techniques, ultrasensitive electrophoresis, in situ hybridization, and histopathologic techniques. SETTING: All patients were seen in the intensive care unit of different university hospitals. PATIENTS: All patients were critically ill with sepsis. They had been given massive doses of corticosteroids in combination with variable doses of neuromuscular blocking agents. All patients developed paralysis of spinal nerve-innervated muscles. On the other hand, cranial nerve-innervated muscle and sensory and cognitive functions were well maintained after discontinuation of treatment with neuromuscular blocking agents. INTERVENTION: Muscle biopsy samples were obtained and electrophysiologic examinations were performed in all patients. MEASUREMENTS AND MAIN RESULTS: The major observations in patients with acute quadriplegic myopathy were, as follows: a) a general decrease in myofibrillar protein content; b) specific but highly variable partial or complete loss of myosin and myosin-associated proteins; c) very low thick-filament/thin-filament protein ratios; d) absence of myosin messenger RNA; and e) a dramatically impaired muscle cell force-generating capacity in the acute phase of acute quadriplegic myopathy. During clinical improvement, normal expression of myosin messenger RNAs, reexpression of thick-filament proteins, and increased specific tension were observed. CONCLUSIONS: Acute quadriplegic myopathy is associated with a specific decrease in thick-filament proteins related to an altered transcription rate. Although the decreased content of thick-filament proteins is important for prolonged muscle weakness, it is not the primary cause of muscle paralysis in the acute stage, during which impaired muscle membrane excitability probably plays a more significant role. Several factors contribute to this condition, but the action of corticosteroids seems to be the predominant one, along with potentiation by neuromuscular blocking agents, immobilization, and probably also concurrent sepsis.

Acute Disease↗
PubMed1999

The effects on resting ventilation of intravenous infusions of morphine or sameridine, a novel molecule with both local anesthetic and opioid properties.

UNLABELLED: Sameridine has both local anesthetic and partial mu-opioid receptor agonistic properties. The aim of this single-blinded, randomized, three-way cross-over study of 12 subjects was to investigate the effects on resting ventilation of two doses of sameridine: 0.15 mg/kg (S-Small) and 0.73 mg/kg (S-Large) compared with 0.10 mg/kg morphine. Each drug was infused IV over 20 min. Ventilation was measured by pneumotachography and in-line capnography, and sedation was rated by the subjects using a visual analog scale (VAS). Plasma was collected and analyzed for sameridine and morphine. At the end of drug infusion, minute ventilation (VE) and tidal volume (VT) were reduced in the S-Large group, and VE was reduced in the morphine group. End-tidal CO2 increased in both groups (P < 0.05), but respiratory rates remained unchanged. In the S-Small group, no ventilatory changes were recorded. In the S-Large group, the median sedation score was 6.8 cm with corresponding values in the morphine and S-Small groups of 3.3 and 2.5 cm, respectively. There was a relationship between the plasma concentration of sameridine and the depression of ventilation. We conclude that sameridine influences resting ventilation and that this effect is directly related to plasma concentrations of sameridine. From a ventilatory aspect, a clinical dose of sameridine with both local anesthetic and opioid properties seems safe. IMPLICATIONS: Sameridine, a molecule with both local anesthetic and analgesic properties, impaired resting ventilation after a large IV dose (0.73 mg/kg), more so than 0.10 mg/kg IV morphine. A clinical dose of sameridine (0.15 mg/kg) did not have any effects on ventilation.

Adult↗
PubMed1998

Carotid body chemoreceptor function is impaired by vecuronium during hypoxia.

BACKGROUND: Neuromuscular blocking agents reduce the human ventilatory response to hypoxia at partial neuromuscular block. It was hypothesized that vecuronium impairs carotid body chemoreceptor function during hypoxia. METHOD: The effect of systemic administration of vecuronium on single chemoreceptor activity during hypoxia, as recorded from a single nerve fiber preparation of the carotid sinus nerve, was studied in seven mechanically ventilated New Zealand White rabbits during continuous thiopental anesthesia. During normoventilation, the isocapnic hypoxic chemosensitivity of the single carotid body chemoreceptor was measured at four levels of oxygenation; these measurements were repeated at six separate occasions: control recording before injection, after intravenous administrations of 0.1 mg and 0.5 mg of vecuronium, and then at three occasions during a 90-min recovery period. Chemoreceptor chemosensitivity during isocapnic hypoxia was expressed as a hyperbolic function: Chemoreceptor output (Hz) = a + b x PaO2(-1) (mmHg). RESULTS: Chemosensitivity was reduced after both 0.1 mg and 0.5 mg vecuronium intravenous administration compared with control measurements; the hypoxic response curve was significantly depressed after both doses (P < 0.05). Notably, there was variation in the effect of vecuronium; some chemoreceptor preparations showed only minimal impairment, whereas some showed an almost abolished response to hypoxia. The chemosensitivity remained significantly depressed at 30 and 60 min but had recovered spontaneously at 90 min after 0.5 mg vecuronium. DISCUSSION: It is concluded that vecuronium depresses carotid body chemoreceptor function to a varying extent during hypoxia and that the depression recovers spontaneously.

Action Potentials↗
PubMed1997

Functional assessment of the pharynx at rest and during swallowing in partially paralyzed humans: simultaneous videomanometry and mechanomyography of awake human volunteers.

BACKGROUND: Functional characteristics of the pharynx and upper esophagus, including aspiration episodes, were investigated in 14 awake volunteers during various levels of partial neuromuscular block. Pharyngeal function was evaluated using videoradiography and computerized pharyngeal manometry during contrast bolus swallowing. METHODS: Measurements of pharyngeal constrictor muscle function (contraction amplitude, duration, and slope), upper esophageal sphincter muscle resting tone, muscle coordination, bolus transit time, and aspiration under fluoroscopic control (laryngeal or tracheal penetration) were made before (control measurements) and during a vecuronium-induced partial neuromuscular paralysis, at fixed intervals of mechanical adductor pollicis muscle train-of-four (TOF) fade; that is, at TOF ratios of 0.60, 0.70, 0.80, and after recovery to a TOF ratio > 0.90. RESULTS: Six volunteers aspirated (laryngeal penetration) at a TOF ratio < 0.90. None of them aspirated at a TOF ratio > 0.90 or during control recording. Pharyngeal constrictor muscle function was not affected at any level of paralysis. The upper esophageal sphincter resting tone was significantly reduced at TOF ratios of 0.60, 0.70, and 0.80 (P < 0.05). This was associated with reduced muscle coordination and shortened bolus transit time at a TOF ratio of 0.60. CONCLUSIONS: Vecuronium-induced partial paralysis cause pharyngeal dysfunction and increased risk for aspiration at mechanical adductor pollicis TOF ratios < 0.90. Pharyngeal function is not normalized until an adductor pollicis TOF ratio of > 0.90 is reached. The upper esophageal sphincter muscle is more sensitive to vecuronium than is the pharyngeal constrictor muscle.

Adult↗
PubMed1997

Sequestration of vecuronium bromide during extremity surgery involving use of a pneumatic tourniquet.

BACKGROUND: We hypothesized that sequestration of a neuromuscular blocking agent could occur during surgery involving use of an extremity tourniquet and cause changes in neuromuscular function after tourniquet release. METHODS: Sixteen patients scheduled for total knee replacement were randomized to one of two groups. In Group I, 10 patients were administered 0.1 mg/kg of vecuronium 5 minutes prior to inflation of a pneumatic tourniquet; in Group II, 6 patients were administered 0.1 mg/kg of vecuronium after inflation of the tourniquet. The twitch (T1) and train-of-four (TOF) were analyzed before and after release of the tourniquet, as was the rate of recovery of T1 and TOF. Serial vecuronium plasma levels were drawn during the study. RESULTS: The T1 and TOF responses and the T1 and TOF recovery rates were not significantly different between groups at tourniquet deflation. In Group I, after release of the tourniquet, T1 and TOF recovery rate decreased significantly over a 10-min period (10% +/- 3 to 4% +/- 4 and 0.12 +/- 0.06 to 0.06 +/- 0.04, mean +/- SD, respectively); in Group II, T1 and TOF recovery rate increased significantly over a 10-min period following deflation of the tourniquet (10% +/- 6 to 14% +/- 7 and 0.10 +/- 0.03 to 0.18 +/- 0.02, respectively). Changes in pharmacodynamics were temporally associated with transient but statistically significant changes in vecuronium plasma levels. Overall pharmacokinetics during the study period were comparable between groups. After administration of neostigmine 30-40 micrograms/kg i.v. all subjects in both groups showed complete TOF recovery within 15 min. CONCLUSIONS: Sequestration of a bolus dose of vecuronium, by a pneumatic tourniquet, causes transient changes in pharmacokinetics and pharmacodynamics. These changes are of limited clinical importance and do not affect reversibility of neuromuscular block.

Hemostasis, Surgical↗
PubMed1996

Vecuronium-induced depression of phrenic nerve activity during hypoxia in the rabbit.

We investigated the effects of a close carotid injection of vecuronium on changes in phrenic nerve activity during different states of oxygenation. Experiments were performed on normothermic and mechanically ventilated adult New Zealand White rabbits with a tracheostomy under continuous thiopental infusion. Carotid arteries and carotid bodies were identified bilaterally followed by glomectomy on the contralateral side and positioning of a lingual artery catheter with its tip located in the carotid bifurcation on the ipsilateral side. From the dissected ipsilateral C-4 nerve root, changes in integrated phrenic nerve activity (IPA) were recorded after isocapnic step reductions from hyperoxia to normoxia (fraction of inspired oxygen [FIO2] 0.21, normoxic challenge) and from hyperoxia to moderate hypoxia (FIO2 0.15, hypoxic challenge) immediately after a close carotid bolus injection of either normal saline or 1 or 10 microgram of vecuronium. Arterial blood gases were analyzed during each ventilatory state. Phrenic nerve response to hypoxia expressed as chemosensitivity (Sch) was computed as the relative change in phrenic nerve activity per unit decrease in arterial oxygen saturation (Sao2), that is: Sch = (IPA challenge/IPA hyperoxia) - 1/Sao2 hyperoxia - Sao2 challenge. Hypoxic challenges were associated with reduced phrenic nerve response (Sch) after injection of 1 and 10 micrograms of vecuronium compared with normal saline. During normoxic challenges, no change occurred after 1 microgram, but reduced chemosensitivity was seen after 10 micrograms of vecuronium. We conclude that vecuronium depresses phrenic nerve activity during hypoxia.

Animals↗
PubMed1996

Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents.

Based on an international consensus conference held in Copenhagen in the autumn of 1994, a set of guidelines for Good Clinical Research Practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents are presented. The guidelines are intended to be a help for people working in this research field, and it is hoped that the guidelines will assist researchers, editors, and drug companies to enhance the quality of their pharmacodynamic studies of neuromuscular blocking agents.

Clinical Trials as Topic↗
PubMed1996

Reduced hypoxic chemosensitivity in partially paralysed man. A new property of muscle relaxants?

BACKGROUND: It was hypothesized that non-depolarizing neuromuscular blocking agents impair hypoxic chemosensitivity in man. METHODS: In thirty randomly allocated male volunteers the hypoxic and hypercarbic ventilatory responses were measured during partial paralysis (TOF ratio 0.70) due to either atracurium (n = 10), pancuronium (n = 10) or vecuronium (n = 10). RESULTS: Hypoxic ventilatory responses were depressed by 306, 287 and 296% (mean SD) at steady-state infusion of atracurium, pancuronium and vecuronium, respectively. At a TOF ratio of > 0.90, the HVR was not different from control measurements. CONCLUSION: It is concluded that non-depolarizing neuromuscular blocking agents impair hypoxic ventilatory regulation. Further experimental studies are warranted to fully describe the mechanism(s) responsible for this interaction.

Atracurium↗
PubMed1996

Fasting guidelines in different countries.

Abstention from food and drink prior to anaesthesia remains a cornerstone in safe practice. Despite the lack of scientific support, previous guidelines, similar for fluids and solids, have for more than three decades more often than not recommended "nil by mouth" ("nothing-per-os"; "NPO" in the US) after midnight or a fixed duration of time. Based on an increased number of studies of relevance to the duration of preoperative fasting, reviews on this subject concerning both adults (1) and children (2) and a large number of editorials (3-7), have recently been published. Since there may be a discrepancy between conclusions based on scientific studies and the current routine practice-this presentation is intended to survey the current recommendations in different countries and how they relate to publications on the subject. Opinions are mainly derived from officers of associations linked to The World Federation for Anaesthesiologists (WFSA) and from current literature.

Adult↗
PubMed1994

Ventilation and neuromuscular blocking drugs.

Ventilatory failure after administration of neuromuscular blocking agents is an important factor in anaesthesia-related perioperative morbidity and mortality. Improved knowledge and new monitoring methods may avoid ventilatory failure caused by incomplete recovery of neuromuscular function in the postoperative period. Central respiratory muscles are less sensitive than, and their time course of neuromuscular block is different from those of, pharyngeal muscles and those of the upper airway. Differences in potency and time course of neuromuscular block may lead to incorrect assessment of ventilatory function during onset and recovery. Even if recovery of the mechanical adductor pollicis train-of-four (TOF) response to a ratio of 0.70 has previously been associated with adequate ventilatory capacity, it is now shown that hypoxic ventilatory responses may be markedly reduced despite adequate respiratory force at a TOF ratio of 0.70. Hence, partial paralysis may interfere with ventilatory regulation in hypoxaemia. Consequently, monitoring neuromuscular function by peripheral nerve stimulation in one muscle yields limited information about total ventilatory capacity, especially the function of the upper airway and ventilatory regulation. Therefore, neuromuscular monitoring should be used with caution during recovery and should always be combined with bedside clinical tests if possible.

Humans↗
PubMed1994

The effect of hypothermia on adductor pollicis twitch tension during continuous infusion of vecuronium in isoflurane-anesthetized humans.

The effect of total body cooling on force of contraction of the adductor pollicis was determined during a constant rate infusion of vecuronium. Anesthesia was induced with thiopental and maintained with isoflurane/nitrous oxide in eight volunteers (study group) and seven surgical patients (control group). After train-of-four (TOF) stimulation of the ulnar nerve, we measured the amplitude of the first response (T1) in the train and the ratio of the fourth-to-first response (TOF ratio). Vecuronium was then administered as an intravenous (i.v.) bolus, 25 micrograms/kg, followed by continuous i.v. infusion, 25 micrograms.kg-1 x h-1; central body (core) temperature was maintained stable for 60 min, at the end of which T1 and TOF responses were constant. In the study group, core temperature was then reduced (using circulating-water blankets) by a mean of 2.6 degrees C, decreasing the T1 and TOF ratio, respectively, by 19% and 18% per degrees C reduction in adductor pollicis temperature. Normothermia was maintained in the control group for a mean of 111 min, with no significant change in T1 and TOF responses. We conclude that, during a constant-rate infusion of vecuronium, the magnitude of neuromuscular block increases significantly when adductor pollicis temperature decreases secondary to core cooling.

Adult↗
PubMed1994

Pharmacodynamics and pharmacokinetics of rocuronium following continuous infusion in patients during intravenous anaesthesia.

After an initial bolus dose (0.6 mg kg-1), 10 patients received a continuous infusion of rocuronium, initially at 0.5 mg kg-1h-1, and then adjusted to maintain 90% twitch depression. Blood samples were analysed for 420 min after switching off the infusion. The dose required to maintain the block was 595 +/- 146 micrograms kg-1h-1, 7-9 times that reported for vecuronium under similar conditions. The pharmacokinetic parameters (volume of distribution at steady state, 309 +/- 80 ml kg-1, plasma clearance 4.5 +/- 1.96 ml kg-1 min-1, and elimination half-life 107 +/- 37 min) were similar to those previously reported after a large single bolus.

Adult↗
PubMed1993

Effect of a vecuronium-induced partial neuromuscular block on hypoxic ventilatory response.

BACKGROUND: A previous study has demonstrated a decrease in the hypoxic ventilatory response in volunteers partially paralyzed with vecuronium. However, in this study, hypocapnia was allowed to occur. Because hypocapnia counteracts the ventilatory response to hypoxia during partial vecuronium-induced neuromuscular block and isocapnia, the hypoxic ventilatory response (HVR) was tested in 10 awake volunteers. METHODS: To avoid hypocapnia, the resting hyperoxic control end-tidal PCO2 was increased to 43.3 +/- 2.4 mmHg, raising inspiratory minute ventilation (VI) to 140 ml.kg-1.min-1. Hypoxic ventilatory response (delta VI/delta SpO2, L.min-1.%-1) was measured during a 5-min isocapnic step reduction to a mean arterial hemoglobin oxygen saturation (SpO2) of 84.8 +/- 1.4%. Immediately thereafter, hypercapnic ventilatory response (HCVR; delta VI/delta PETCO2, L.min-1.mmHg-1) was determined at the end of a 6-min step increase of PETCO2 to 50.5 +/- 2.7 mmHg. During a subsequent 30-40-min pause, an intravenous infusion of vecuronium was adjusted to reduce the adductor pollicis train-of-four ratio to 0.70, as monitored using mechanomyography. Ventilatory parameters, HVR and HCVR, were then redetermined. RESULTS: Resting VI, PETCO2, and SpO2 were unchanged by drug infusion. Hypoxic ventilatory response decreased from control (a) of 0.97 +/- 0.43 to 0.74 +/- 0.41 L.min-1.%-1 (P < 0.02) during drug infusion (b), while HCVR was unchanged (a = 1.91 +/- 0.82, b = 1.62 +/- 0.46 L.min-1.mmHg-1; NS). To correct HVR for possible vecuronium-induced respiratory muscle weakness or otherwise altered central nervous system reactivity, the drug/control ratio (HVRb/a) was divided by the associated HCVRb/a ratio. This HVR index, FHVR, was 0.84 +/- 0.12 (P < 0.01). CONCLUSIONS: We conclude that a vecuronium-induced partial neuromuscular block impairs HVR more than it does HCVR in humans, suggesting an effect of vecuronium on carotid body hypoxic chemosensitivity.

Adult↗
PubMed1993

Halothane-diethyl ether azeotrope anesthesia under primitive conditions: guidelines for neuromuscular blockade with vecuronium.

The dose-response relationship for vecuronium during anesthesia with the azeotropic mixture of halothane and diethyl ether (HE) (66 ml of halothane mixed with 34 ml of ether in the same bottle)/oxygen was compared with halothane/nitrous oxide/oxygen anesthesia. The HE is not explosive and has preserved many of the advantageous properties of diethyl ether, making it an attractive anesthetic drug under difficult circumstances such as war or civil disaster. If muscular relaxation is needed in military anesthesia, it is essential to use a short- to medium-acting compound that can be stored without refrigeration. Vecuronium bromide fulfills these criteria. The study was conducted on 20 young (mean 24 years, range 18-31), ASA I patients. Using adductor pollicis mechanomyography and a cumulative dose technique, individual dose-response curves for vecuronium were constructed. Care was taken to keep peripheral and core temperatures normal and the times of exposure to inhalational gases equal. The results were analyzed by the log-probit method. During HE anesthesia, ED50 for vecuronium was 22 +/- 2 micrograms kg-1 (mean +/- SE) and ED90 was 49 +/- 8 micrograms kg-1. During halothane/nitrous oxide anesthesia, ED50 for vecuronium was 18 +/- 2 micrograms kg-1 (mean +/- SE) and ED90 was 39 +/- 7 micrograms kg-1. The dose-response relationships for vecuronium were similar during HE anesthesia and halothane/nitrous oxide anesthesia.

Adolescent↗
PubMed1992

Attenuated ventilatory response to hypoxaemia at vecuronium-induced partial neuromuscular block.

The effect of a partial neuromuscular block on the ventilatory response to hypercarbia and to hypoxaemia was studied in 11 non-anaesthetized male subjects. Respiratory frequency, tidal volume, minute volume, respiratory timing and drive were measured during air breathing and during stimulation by hypercarbia and hypoxaemia. The ventilatory response was defined as the ratio between, respectively, tidal volume and minute volume during ventilation stimulated by hypercarbia and hypoxaemia compared to measurements during air breathing. The ventilatory measurements were repeated on three separate occasions: before neuromuscular block was established, during an infusion of vecuronium aiming at a mechanical adductor pollicis train-of-four (TOF) ratio of 0.70, and after the infusion had been stopped and the neuromuscular block had spontaneously recovered to a TOF ratio of > 0.90. Resting ventilation during air breathing remained with minor variations throughout the experiment. The ventilatory response to hypercarbia was not affected at a TOF ratio of 0.70 as compared to measurements before vecuronium and at a TOF ratio of > 0.90. In contrast, the ventilatory response to hypoxaemia was markedly reduced at a TOF ratio of 0.70. We conclude that a mechanical TOF ratio of 0.70 following vecuronium may be associated with an inadequate ventilatory response to hypoxaemia.

Adult↗