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Biomedical subjects

D B Coursin

Publications and source records attributed to D B Coursin.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1994

Applied pharmacology of common neuromuscular blocking agents in critical care.

While all neuromuscular blocking agents (NMBAs) effectively interrupt neuromuscular transmission, it must be emphasized that these drugs are completely devoid of analgesic, sedative, or amnestic properties. The increasing use of NMBAs in the ICU requires familiarity with their basic pharmacologic properties, as well as an appreciation of potential problems associated with chronic (> 24 hrs) neuromuscular blockade. Although NMBAs possess an impressive safety record, the majority of recommendations for neuromuscular blocker use in the ICU are extrapolated from short-term perioperative studies in healthy patients. NMBAs are structurally related to acetylcholine and their main site of action is the postjunctional nicotinic acetylcholine receptor, although prejunctional interaction may be an important component of total activity. These drugs act to either sustain a depolarization at the postjunctional membrane (succinylcholine), or they inhibit neuromuscular transmission by a competitive (non-depolarizing) blocking mechanism. Adverse hemodynamic consequences may result from concurrent stimulation of muscarinic receptors, autonomic ganglia, histamine, or catecholamine release associated with some agents. The metabolism and excretion of NMBAs may be altered in ICU patients with end-organ dysfunction, concurrent medications, electrolyte, acid-base, and nutritional abnormalities, along with underlying nervous system and muscle pathology. Prolonged weakness after discontinuation of NMBAs is increasingly recognized after these agents are used for extended periods. This phenomenon may be related to alterations in the pharmacokinetics and pharmacodynamics, along with altered physiology of the neuromuscular junction, nervous system, or muscle, or other undefined toxic effects. A sound knowledge of the basic physiology of the neuromuscular junction, neuromuscular blocker pharmacology, and standard techniques to assess the degree of neuromuscular blockade provides the rationale for drug selection when paralysis is indicated in ICU patients.

Critical Care↗
PubMed1993

Immunolocalization of manganese superoxide dismutase in normal and transgenic mice expressing the human enzyme.

The localization of manganese superoxide dismutase (MnSOD) was determined using immunohistochemistry of various tissues of normal and transgenic mice which express the human enzyme, with emphasis on studies of mouse kidney and lung. Mouse kidney and lung were studied using both frozen section analysis and paraffin sections following fixation in a variety of fixatives. Formalin fixation resulted in a loss of antigenicity, while fixation in zinc formalin or B5 fixative gave results similar to those from frozen sections. Immunoperoxidase studies using antibodies to MnSOD showed greater staining in transgenic kidney or lung than in identical tissues in normal mice when appropriate fixation was used. In contrast, equal immunostaining was obtained in kidney or lung from normal and transgenic mice when antibodies to catalase or copper zinc superoxide dismutase were utilized. Immunogold ultrastructural analysis of MnSOD localization for lung and kidney was also performed. As compared to normal mice, transgenic mice exhibited greater staining of the mitochondria of kidney interstitial fibroblasts and glomerular, endothelial, and smooth muscle cells. In the lungs of transgenic animals, all cells showed increased staining; smooth muscle cells demonstrated the most marked increase in immunolabelling. The results indicate that these transgenic mice overexpress MnSOD in their mitochondria, and that this occurs selectively in at least some mesenchymal tissues.

Animals↗
PubMed1992

A national survey on the practice patterns of anesthesiologist intensivists in the use of muscle relaxants.

OBJECTIVE: To determine the practice patterns of anesthesiologist intensivists (with the special certificate of competence in critical care medicine from the American Board of Anesthesiology) in the use of neuromuscular blocking drugs, in the ICU setting. DESIGN: A survey. PARTICIPANTS: All anesthesiologists with the special certificate of competence in critical care (n = 374) were selected for this study. Of the 339 who could be contacted and who were still actively practicing, 185 (55%) completed the survey. RESULTS: In the ICU setting, anesthesiologist intensivists most commonly used vecuronium (52%) administered by bolus injection, bolus injection followed by infusion, or by continuous infusion. The most frequent indication for muscle relaxation was facilitation of mechanical ventilation (89%). Neuromuscular blockade was most commonly monitored clinically (55%), with only 34% of respondents using a peripheral nerve stimulator. All respondents indicated the concomitant use of sedatives or narcotics with muscle relaxants. CONCLUSIONS: This study was created to address the dearth of information regarding actual usage of muscle relaxants in the ICU setting. The survey population was chosen as one with great familiarity in the use of muscle relaxants. The 55% response rate was significantly greater than the expected response rate for a single mailing survey. In the ICU setting, neuromuscular blocking drugs are most frequently used to facilitate mechanical ventilation. The prevalence of vecuronium use is of interest in light of recent case reports of prolonged neuromuscular blockade after long-term vecuronium administration. The low frequency of peripheral nerve stimulator monitoring during muscle relaxation may contribute, in part, to the problem of prolonged blockade after drug withdrawal. Muscle relaxants are not used in the absence of sedation and/or analgesia by this practitioner population.

Anesthesiology↗
PubMed1992

Immunolocalization of antioxidant enzymes and isozymes of glutathione S-transferase in normal rat lung.

Polyclonal antisera to manganese and copper-zinc superoxide dismutases, catalase, glutathione peroxidase (GPx), and isozymes of glutathione S-transferase (liver and placental isolates, GST-L and GST-P, respectively) were used to localize these enzymes in normal rat lung by immunostaining. Light-microscopic results, using an immunoperoxidase technique, were expanded on by electron-microscopic immunogold localization. The findings were consistent with previous biochemical work. However, both GPx and GST-P were predominantly localized to extracellular connective tissue of the lung. These findings demonstrate the basal antioxidant enzyme phenotypes for parenchymal lung tissue at light- and electron-microscopic levels. Significant components of enzymatic defense to oxidant stress are heterogeneously distributed throughout rat lung tissue including both epithelial cell surfaces and the extracellular matrix.

Animals↗