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Biomedical subjects

D B Coursin

Publications and source records attributed to D B Coursin.

At least 19 recordsLinked to original sources
PubMed1996

Pulmonary effects of short term selenium deficiency.

BACKGROUND: Selenium dependent glutathione peroxidase (GPx) reduces hydrogen peroxide (H2O2) and organic hydrogen peroxides in both normal and pathological states. Chronic dietary deficiency of selenium results in a gradual decrease in GPx and altered response to environmental stress. However, glutathione-S-transferase (GST) isozymes may increase and compensate for chronic GPx deficiency. The pattern of antioxidant enzyme activity and immunolocalisation of various enzymes in rat lung has not been described in short term (< 3 weeks) acute selenium deficiency. METHODS: The time course of GPx depletion from rat lung (measured every five days in subgroups of rats) during acute dietary selenium deficiency was evaluated. After 20 days of depletion, enzyme activity of lung GPx, catalase, superoxide dismutase (SOD), glutathione reductase (GR), glucose-6-phosphodiesterase (G-6-PD), and GST were determined. Immunohistochemical localisation of GPx and SOD was also performed. The response to lethal hyperoxia (> 95%) in control and selenium deficient rats was then established. RESULTS: At 20 days, lung GPx activity in the rats fed a selenium deficient diet was one third less than in control animals who received a normal diet, while changes in blood enzymes between control and deficient animals were similar. Other lung enzyme activities remained normal with the exception of cyanide inhibited SOD activity measured in selenium deficient rat lungs which declined to approximately 50% of normal. Immunohistochemical localisation of GPx showed a generalised loss of the enzyme throughout the lung parenchyma with some possible sparing of activity in epithelial cells of the bronchioles. When exposed to lethal hyperoxia, selenium deficient animals were more susceptible than control rats. CONCLUSIONS: This is the earliest time at which dietary selenium deficiency has been shown to produce moderate loss of GPx activity. This change in activity was associated with increased susceptibility to pulmonary oxidant stress. However, the role of decreased SOD activity (presumed to represent copper, zinc SOD), although unexpected, may have been a major contributor to increased damage from hyperoxia. These results emphasise the complex potential interaction of elemental deficiency with the natural antioxidant response to lethal hyperoxia.

Animals↗
PubMed1996

Pharmacodynamics and pharmacokinetics of milrinone administration to increase oxygen delivery in critically ill patients.

OBJECTIVES: The positive inotropic and vasodilator actions of phosphodiesterase (PDE) inhibitor drugs may offer therapeutic alternatives to beta-agonists in critically ill patients. We hypothesized that milrinone administration would increase cardiac index (CI) and oxygen delivery (Do2) in ICU patients, and that a pharmacokinetic model previously developed in cardiac surgery patients may be used to predict milrinone plasma concentrations in a medical-surgical ICU population. SETTING: ICU in two tertiary-care, university medical centers. DESIGN AND INTERVENTIONS: A prospective, open-label, multicenter, dose-escalating study in three successive groups of eight ICU patients who received a 10-min loading dose of milrinone (25 micrograms/kg [LOW], 50 micrograms/kg [MED], and 75 micrograms/kg [HIGH]). In addition, all patients then received a milrinone infusion of 0.5 microgram/kg/min for 1 h. MEASUREMENTS: Hemodynamic measurements included heart rate (HR); mean arterial, pulmonary artery, central venous, and pulmonary artery occlusion pressures; and thermodilution cardiac output. Oxygen transport indexes included arterial and venous blood oxygen tensions to determine Do2 and oxygen consumption (Vo2). Data were analyzed by univariate repeated measures analysis of covariance, with baseline values utilized as covariate regressors. RESULTS: Twenty-four adult ICU patients 20 to 84 years of age completed the study. The three groups did not differ, except that the patients in the MED group were significantly older (67 +/- 4 years, mean +/- SEM) compared with either the patients in the LOW (48 +/- 7 years) or HIGH (47 +/- 6 years) group. While HR did not change in the LOW group (90 +/- 4 to 93 +/- 3 beats/min), HR increased significantly in the HIGH group (94 +/- 5 to 112 +/- 8 beats/min) (baseline to 60 min infusion time points). All milrinone doses increased both CI and Do2. At the end of the 10-min loading dose, CI increased 0.3 L/min/m2 in the LOW group, 1.1 L/min/m2 in the MED group, and 0.9 L/min/m2 in the HIGH group. Do2 increased 8% in the LOW group, 33% in the MED group, and 23% in the HIGH group, similar to the changes in CI. Mixed venous oxygen saturation increased 3 to 5% during the 10-min loading dose of milrinone. During this same time period, mean arterial pressure decreased 6 to 16% and pulmonary artery pressures decreased 9 to 15%. Peak plasma milrinone concentrations increased as a function of the loading dose (159 +/- 9 ng/mL in the LOW group, 302 +/- 33 ng/ml in the MED group, and 411 +/- 45 ng/mL in the HIGH group). However, milrinone concentrations were similar in all three groups after the 1-h infusion; 113 +/- 14 ng/ml (LOW), 147 +/- 22 ng/mL (MED), and 119 +/- 14 ng/ml (HIGH). In all patients with final plasma milrinone concentrations greater than 100 ng/mL (15/23), the CI increased by at least 0.4 L/min/m2 (range, 0.4 to 1.8 L/min/m2). CONCLUSIONS: Our study confirms that a milrinone loading dose of 50 micrograms/kg/min followed by an infusion of 0.5 microgram/kg/min achieves adequate plasma concentrations of 100 ng/mL or greater, which significantly increases both CI and Do2. In addition, a previously established pharmacokinetic model of milrinone disposition is confirmed in this mixed ICU population.

Adult↗
PubMed1996

Assessment of sedation, analgesia, and neuromuscular blockade in the perioperative period.

Identification of adequate pain relief, sedation, and neuromuscular blockade in the perioperative period (be it for monitored anesthesia care, conscious sedation, ICU analgesia or sedation, or during intraoperative care) continues to be a challenge. Current subjective and objective techniques have been reviewed. The combination of clinical judgement, physiological response, and selected monitoring tools provide the current standard of care used to optimize patient care and comfort. Future directions in assessing pain control, adequacy of sedation, and degree of neuromuscular blockade include: (1) simplified scoring scales, (2) computerized analysis of the EEG, (3) computerized evoked potentials, (4) portable accelerography of electromyography for determination of neuromuscular blockade, and (5) closed loop system for delivery of analgesics, sedatives, and paralytics.

Analgesia↗
PubMed1996

An immunohistochemical analysis of antioxidant and glutathione S-transferase enzyme levels in normal and neoplastic human lung.

Samples of normal human lung and six major types of human lung carcinomas were immunostained for antioxidant enzymes (manganese and copper, zinc superoxide dismutases, catalase, and glutathione peroxidase) and six isoenzymes of glutathione S-transferase staining was generally low in tumor cells compared with the high level of staining noted in respiratory epithelium. A notable exception was heterogeneity in immunostaining for manganese superoxide dismutase in lung adenocarcinoma, which showed both positive and negative cells in the same tumor. Tumor stromal cells (fibroblast-appearing cells) often showed strong immunostaining for manganese superoxide dismutase, while stromal cells were negative for other antioxidant and glutathione S-transferase enzymes. None of the carcinomas studied had significant levels of catalase or glutathione peroxidase; this finding has potential clinical relevance since it indicates that these tumors cannot detoxify hydrogen peroxide. The low levels of antioxidant and glutathione S-transferase enzymes in tumor cells is consistent with the hypothesis that these enzymes are markers of cell differentiation.

Adenocarcinoma↗
PubMed1995

Comparison of the infusion requirements and recovery profiles of vecuronium and cisatracurium 51W89 in intensive care unit patients.

The selection and administration of neuromuscular blocking (NMB) drugs in intensive care unit (ICU) patients remain controversial. We compared the dose-response and recovery pharmacodynamics of a new intermediate-acting NMB drug, cisatracurium besylate, to the intermediate-acting NMB drug, vecuronium (VEC), in a prospective, randomized, double-blind, multicenter study in critically ill adults. After informed consent, 58 mechanically ventilated ICU patients from five medical centers were randomized to receive either cisatracurium or VEC. Fifty-four of the 58 patients received NMB drugs before entering this study but demonstrated at least partial recovery (> or = one twitch) in the train-of-four (TOF) response before initiation of the NMB study drug. NMB drug infusion was titrated by peripheral nerve stimulation to maintain at least one twitch in the TOF response. NMB drugs were infused for 1-5 days. After discontinuation of NMB drug infusion, recovery of neuromuscular transmission was monitored with an accelerometer. NMB drug infusion for 28 cisatracurium patients averaged 2.6 +/- 0.2 (mean +/- SEM) micrograms.kg-1.min-1 with a mean duration of 80 +/- 7 h. After discontinuing cisatracurium administration, recovery to 70% TOF ratio averaged 68 +/- 13 min. The mean infusion rate for 30 VEC patients was 0.9 +/- 0.1 micrograms.kg-1.min-1 with a mean duration of 66 +/- 12 h. Neuromuscular recovery after VEC averaged 387 +/- 163 min, which was significantly longer (P = 0.02) than that after cisatracurium. Prolonged recovery of neuromuscular function after discontinuation of NMB drug infusion (identified by the primary investigator at each medical center) was reported in two cisatracurium patients and 13 VEC patients (P = 0.002), and occurred despite the routine use of neuromuscular twitch monitoring. Seven VEC and one cisatracurium patients died during the infusion of study drug or within 48 h after discontinuation of the NMB drug infusion. In summary, we found recovery of neuromuscular function after discontinuation of NMB drug infusion in ICU patients is significantly faster with cisatracurium than with VEC. In addition, routine neuromuscular monitoring was not sufficient to eliminate prolonged recovery and myopathy in ICU patients.

Adult↗
PubMed1995

Double-blind, randomized, multicenter study of doxacurium vs. pancuronium in intensive care unit patients who require neuromuscular-blocking agents.

OBJECTIVE: To compare the neuromuscular-blocking and hemodynamic effects of doxacurium vs. pancuronium administered by intermittent bolus to intensive care unit (ICU) patients who required neuromuscular block to facilitate mechanical ventilation for > or = 24 hrs. DESIGN: A multicenter, prospective, double-blind, randomized study comparing doxacurium, a new benzylisoquinolone neuromuscular-blocking agent, with pancuronium. SETTING: ICUs of three tertiary care hospitals. PATIENTS: Forty critically ill patients (29 male, 11 female) with an average age of 52.5 yrs (range 19 to 80). INTERVENTIONS: With approval of our Institutional Review Boards and after obtaining informed consent, 40 critically ill patients were entered into the study. Histories and the results of physical examinations were recorded, laboratory data were collected, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated during the 8 hrs before the start of the study medication. Patients received either doxacurium (initial dose of 0.04 mg/kg) or pancuronium (initial dose of 0.07 mg/kg) by bolus injection with continuous measurement of vital signs every minute for 15 mins. We measured the degree of neuromuscular blockade using a peripheral-nerve stimulator to measure the Train-of-Four count. Patients were rebolused (doxacurium dose of 0.025 mg/kg, pancuronium dose of 0.05 mg/kg) based on clinical criteria, which were substantiated by measurement of the Train-of-Four count. The neuromuscular-blocking drugs were stopped when the patient no longer required paralysis or after 5 days of therapy, whichever came first. Group comparisons were made using repeated measures analysis of variance, Fisher's exact test, and two sample t-tests, when appropriate. Spearman's rank-correction coefficients were calculated to assess the relationship of onset time and recovery time with all baseline laboratory values and the APACHE II scores. A p < .05 was used to establish statistical significance. MEASUREMENTS AND MAIN RESULTS: There were no differences between the two groups with respect to age, gender, or APACHE II scores. There were no differences between groups in terms of adverse experiences, nor with respect to time of onset of block, number of doses, or the duration of neuromuscular blockade (2.6 vs. 2.2 days for doxacurium vs. pancuronium, respectively). There was a statistically significant increase in heart rate after the initial dose of pancuronium (120 +/- 23 vs. 109 +/- 22 beats/min postinjection vs. preinjection, respectively; p < .05) without any differences noted after doxacurium (107 +/- 21 vs. 109 +/- 21 beats/min, respectively). Furthermore, once neuromuscular block was discontinued, the pancuronium group had a more prolonged and variable recovery time (279 +/- 229 mins) compared with the doxacurium group (138 +/- 46 mins, p < .05). CONCLUSIONS: In critically ill patients requiring neuromuscular block for > 24 hrs, doxacurium was well tolerated without evidence of tachycardia and with a relatively prompt recovery profile.

APACHE↗
PubMed1995

Sedative and neuromuscular blocking drug use in critically ill patients with head injuries.

Sedative and neuromuscular blocking (NMB) drugs are used to facilitate care of head trauma patients requiring mechanical ventilation or therapy of intracranial hypertension. Because no specific regimen is appropriate in all patients, drug selection and utilization exhibit significant regional variation. Sedatives are used to decrease anxiety and diminish awareness of noxious stimuli. Propofol offers particular promise in neurosurgical intensive care. NMB drugs are used in 1% to 10% or more of critically ill patients. Increasingly more information is available to guide the use of NMB drugs for patients suffering head trauma. Broad concerns about these drugs include their use as adjunctive therapy to control intracranial hypertension, the incidence of prolonged weakness or myopathy, the potential for direct neurologic toxicity, and their effect on outcome. Resolution of these issues will improve the use of sedative and NMB drugs in intensive care.

Central Nervous System Diseases↗
PubMed1995

Use of neuromuscular blocking drugs in the critically ill patient.

Neuromuscular blocking drugs are used routinely to facilitate the care of critically ill patients of all ages. This article addresses current uses and concerns about the appropriate administration of these drugs. Several important topics are highlighted, including basic physiology of neuromuscular transmission, blocker pharmacology, drug selection, monitoring, and future areas of research.

Procedural Sedation↗
PubMed1995

Complications associated with sedative and neuromuscular blocking drugs in critically ill patients.

Pharmacologic administration of sedatives is used routinely in the care of the critically ill to enhance patient comfort and optimize care. Long-term administration of NMB drugs is far less frequent but often occurs in patients with greater organ dysfunction. The experience of several authors using NMB drugs in the ICU is summarized in Table 5. Both classes of drugs have potential untoward effects. Some are readily predictable; others are not. NMB drugs enjoy a long record of safe, effective use during the perioperative period, but certain issues linger in defining appropriate administration to critically ill patients. Major concerns focus on the appropriate drug selection and delivery, monitoring, and neuromuscular recovery of patients who receive NMB drugs for longer than 24 hours. The development of myopathy and paresis has been increasingly recognized after prolonged use of NMB drugs in the ICU. Further investigation needs to fully characterize this process, identify those at risk, and outline a mechanism to prevent or limit the injury. Prolonged weakness may occur secondary to changes in the basic pharmacology and elimination of NMB drugs in ICU patients. Pathophysiologic changes in the nerve, muscle, or neuromuscular junction may also play a role in the development of some cases of prolonged weakness or myopathy after discontinuation of NMB drugs. Concerns about the potential for direct or indirect toxicity of NMB drugs to skeletal muscle and in the CNS remain. Resolution of these issues will improve the selection and optimal administration of sedative and NMB drugs in the ICU setting.

Central Nervous System Diseases↗