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ABSTRACT: Ventilator-associated tracheobronchitis (VAT) is considered an intermediate condition between bacterial airway colonization and ventilator-associated pneumonia (VAP). The purpose of this prospective cohort study was to further characterize VAT in terms of incidence, etiology, and impact on patient outcomes.
Patients intubated for >48 h in the surgical and medical ICUs of Barnes-Jewish Hospital were screened daily for the development of VAT and VAP over 1 year. Patients were followed until hospital discharge or death, and patient demographics, causative pathogens, and clinical outcomes were recorded.
A total of 28 patients with VAT and 83 with VAP were identified corresponding to frequencies of 1.4% and 4.0%, respectively. VAP was more common in surgical than medical ICU patients (5.3% vs 2.3%; P<.001), but the occurrence of VAT was similar between surgical and medical patients (1.3% vs 1.5%; P=.845). VAT progressed to VAP in nine patients (32.1%) despite antibiotic therapy. There was no significant difference in hospital mortality between patients with VAP and VAT (19.3% vs 21.4%; P=.789). VAT was caused by a multidrug-resistant (MDR) pathogen in nine cases (32.1%).
VAT occurs less commonly than VAP but at a similar incidence in medical and surgical ICU patients. VAT frequently progressed to VAP, and patients diagnosed with VAT had similar outcomes to those diagnosed with VAP, suggesting that antimicrobial therapy is appropriate for VAT. VAT is also frequently caused by MDR organisms, and this should be taken into account when choosing antimicrobial therapy.
Chest 03/2011; 139(3):513-8. · 5.25 Impact Factor
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Critical care medicine 01/2010; 38(1):338; authore reply 338-9. · 6.37 Impact Factor
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Carrie S Sona,
Jeanne E Zack,
Marilyn E Schallom,
Maryellen McSweeney,
Kathleen McMullen,
James Thomas,
Craig M Coopersmith, Walter A Boyle,
Timothy G Buchman,
John E Mazuski,
Douglas J E Schuerer
[show abstract]
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ABSTRACT: The purpose of this study was to determine the effects of a simple low-cost oral care protocol on ventilator-associated pneumonia rates in a surgical intensive care unit.
Preintervention and postintervention observational study.
Twenty-four bed surgical/trauma/burn intensive care units in an urban university hospital.
All mechanically ventilated patients that were admitted to the intensive care unit between June 1, 2004 and May 31, 2005.
An oral care protocol to assist in prevention of bacterial growth of plaque by cleaning the patients' teeth with sodium monoflurophosphate 0.7% paste and brush, rinsing with tap water, and subsequent application of a 0.12% chlorhexidine gluconate chemical solution done twice daily at 12-hour intervals.
During the preintervention period from June 1, 2003 to May 31, 2004, there were 24 infections in 4606 ventilator days (rate = 5.2 infections per 1000 ventilator days). After the institution of the oral care protocol, there were 10 infections in 4158 ventilator days, resulting in a lower rate of 2.4 infections per 1000 ventilator days. This 46% reduction in ventilator-associated pneumonia was statistically significant (P = .04). Staff compliance with the oral care protocol during the 12-month period was also monitored biweekly and averaged 81%. The total cost of the oral care protocol was US$2187.49. There were 14 fewer cases of ventilator-associated pneumonia, which led to a decrease in cost of US$140 000 to US$560 000 based on the estimated cost per ventilator-associated pneumonia infection of US$10 000 to US$40 000. There was an overall reduction in ventilator-associated pneumonia without a change to the gram-negative or gram-positive microorganism profile.
The implementation of a simple, low-cost oral care protocol in the surgical intensive care unit led to a significantly decreased risk of acquiring ventilator-associated pneumonia.
Journal of Intensive Care Medicine 12/2008; 24(1):54-62.
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New England Journal of Medicine 07/2008; 358(25):2736; author reply 2737-8. · 53.30 Impact Factor
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ABSTRACT: To examine the feasibility and potential utility of a tracheostomy protocol based on a standardized approach to ventilator weaning.
Prospective, observational data collection.
Academic medical center.
Surgical intensive care unit patients requiring mechanical ventilatory support.
None.
Tracheostomy practice in 200 patients was analyzed in relation to spontaneous breathing trial (SBT) weaning. Decision for, and performance of, tracheostomy occurred (median [interquartile range]) 5.0 (3.75-8.0) and 7.0 (5.0-10.0) days following initiation of mechanical ventilation, respectively. Duration of mechanical ventilation was greater in tracheostomy compared with nontracheostomy patients (15.0 [11.0-19.0] vs. 6.0 [4.0-8.0], p < .001). For patients requiring ventilatory support for > or = 20 days, 100% of patients were maintained via tracheostomy. A protocol based on weaning performance, which included technical considerations, was developed. Individuals who failed preliminary weaning assessment or SBT for 3 successive days following 5 days (nonreintubated patients) or 3 days (reintubated patients) of ventilatory support met tracheostomy criteria. The protocol was implemented on a pilot basis in 125 individuals. Of the 55 (44.0%) patients undergoing tracheostomy, 25 (45.5%) did so consistent with criteria. Eighteen patients (32.7%) underwent tracheostomy before the time interval of data collection targeting weaning protocol performance, and 12 patients (21.8%) passed SBT on one or more occasions, were not extubated, and proceeded to tracheostomy.
A standardized approach in which the decision for tracheostomy is based on objective measures of weaning performance may be a means of using this procedure more consistently and effectively.
Critical care medicine 06/2008; 36(6):1742-8. · 6.37 Impact Factor
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Mylène Pezet,
Marie-Paule Jacob,
Brigitte Escoubet,
Dealba Gheduzzi,
Emmanuelle Tillet,
Pascale Perret,
Philippe Huber,
Daniela Quaglino,
Roger Vranckx,
Dean Y Li,
Barry Starcher, Walter A Boyle,
Robert P Mecham,
Gilles Faury
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ABSTRACT: Elastin, the main component of elastic fibers, is synthesized only in early life and provides the blood vessels with their elastic properties. With aging, elastin is progressively degraded, leading to arterial enlargement, stiffening, and dysfunction. Also, elastin is a key regulator of vascular smooth muscle cell proliferation and migration during development since heterozygous mutations in its gene (Eln) are responsible for a severe obstructive vascular disease, supravalvular aortic stenosis, isolated or associated to Williams syndrome. Here, we have studied whether early elastin synthesis could also influence the aging processes, by comparing the structure and function of ascending aorta from 6- and 24-month-old Eln+/- and Eln+/+ mice. Eln+/- animals have high blood pressure and arteries with smaller diameters and more rigid walls containing additional although thinner elastic lamellas. Nevertheless, longevity of these animals is unaffected. In young adult Eln+/- mice, some features resemble vascular aging of wild-type animals: cardiac hypertrophy, loss of elasticity of the arterial wall through enhanced fragmentation of the elastic fibers, and extracellular matrix accumulation in the aortic wall, in particular in the intima. In Eln+/- animals, we also observed an age-dependent alteration of endothelial vasorelaxant function. On the contrary, Eln+/- mice were protected from several classical consequences of aging visible in aged Eln+/+ mice, such as arterial wall thickening and alteration of alpha(1)-adrenoceptor-mediated vasoconstriction. Our results suggest that early elastin expression and organization modify arterial aging through their impact on both vascular cell physiology and structure and mechanics of blood vessels.
Rejuvenation Research 03/2008; 11(1):97-112. · 3.83 Impact Factor
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Douglas J E Schuerer,
Jeanne E Zack,
James Thomas,
Ingrid B Borecki,
Carrie S Sona,
Marilyn E Schallom,
Melissa Venker,
Jennifer L Nemeth,
Myrna R Ward,
Linda Verjan,
David K Warren,
Victoria J Fraser,
John E Mazuski, Walter A Boyle,
Timothy G Buchman,
Craig M Coopersmith
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ABSTRACT: Current guidelines recommend using antiseptic- or antibiotic-impregnated central venous catheters (CVCs) if, following a comprehensive strategy to prevent catheter-related blood stream infection (CR-BSI), infection rates remain above institutional goals based on benchmark values. The purpose of this study was to determine if chlorhexidine/silver sulfadiazine-impregnated CVCs could decrease the CR-BSI rate in an intensive care unit (ICU) with a low baseline infection rate.
Pre-intervention and post-intervention observational study in a 24-bed surgical/trauma/burn ICU from October, 2002 to August, 2005. All patients requiring CVC placement after March, 2004 had a chlorhexidine/silver sulfadiazine-impregnated catheter inserted (post-intervention period).
Twenty-three CR-BSIs occurred in 6,960 catheter days (3.3 per 1,000 catheter days)during the 17-month control period. After introduction of chlorhexidine/silver sulfadiazine-impregnated catheters, 16 CR-BSIs occurred in 7,732 catheter days (2.1 per 1,000 catheter days; p = 0.16). The average length of time required for an infection to become established after catheterization was similar in the two groups (8.4 vs. 8.6 days; p = 0.85). Chlorhexidine/silver sulfadiazine-impregnated catheters did not result in a statistically significant change in the microbiological profile of CR-BSIs, nor did they increase the incidence of resistant organisms.
Although chlorhexidine/silver sulfadiazine-impregnated catheters are useful in specific patient populations, they did not result in a statistically significant decrease in the CR-BSI rate in this study, beyond what was achieved with education alone.
Surgical Infections 09/2007; 8(4):445-54. · 1.80 Impact Factor
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ABSTRACT: Medical errors are common, and physicians have notably been poor medical error reporters. In the SICU, reporting was generally poor and reporting by physicians was virtually nonexistent. This study was designed to observe changes in error reporting in an SICU when a new card-based system (SAFE) was introduced.
Before implementation of the SAFE reporting system, education was given to all SICU healthcare providers. The SAFE system was introduced into the SICU for a 9-month period from March 2003 through November 2003, to replace an underused online system. Data were collected from the SAFE card reports and the online reporting systems during introduction, removal, and reimplementation of these cards. Reporting rates were calculated as number of reported events per 1,000 patient days.
Reporting rates increased from 19 to 51 reports per 1,000 patient days after the SAFE cards were introduced into the ICU (p</= 0.001). Physician reporting increased most, rising from 0.3 to 5.8 reports per 1,000 patient days; nursing reporting also increased from 18 to 39 reports per 1,000 patient days (both p</=0.001). When the SAFE cards were removed, physician reporting declined to 0 reports per 1,000 patient days (p=0.01) and rose to 8.1 (p=0.001) when the cards were returned, similar to nursing results. A higher proportion of physician reports were events that caused harm compared with no effect (p < 0.05).
A card reporting system, combined with appropriate education, improved overall reporting in the SICU, especially among physician providers. Nurses were more likely to use reporting systems than were physicians. Physician reports were more likely to be of events that caused harm.
Journal of the American College of Surgeons 06/2006; 202(6):881-7. · 4.55 Impact Factor
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ABSTRACT: To determine the effect of vasodilatory septic shock-like conditions on vasoconstricting responses to vasopressin and norepinephrine in isolated resistance arteries.
Prospective, randomized animal study.
University research laboratory.
Male adult Sprague-Dawley rats.
Small mesenteric arteries (outside diameter, 50-150 microm) were cannulated and studied in vitro under physiologic conditions. A vasodilatory septic shock-like state was produced by treatment with the nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP), and the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX). Vasoconstricting concentration-response relationships were determined for norepinephrine and vasopressin before and after application of SNAP or SNAP+ IBMX. Synergism between low-dose vasopressin and norepinephrine and between low-dose norepinephrine and vasopressin was determined before and after SNAP or SNAP+IBMX.
Norepinephrine and vasopressin produced concentration-dependent contractions (half-maximal effective concentration [EC(50)] = 2.5 microM and 3.9 nM, respectively) that were significantly inhibited by 1 microM SNAP (EC(50) = 3.6 microM and 8.1 nM, respectively) or 100 microM SNAP + 10 microM IBMX (EC(50) = 10 microM and 8.2 nM, respectively). Low-dose vasopressin significantly increased the responsiveness to norepinephrine (EC50 = 0.5 microM) just as a low-dose norepinephrine significantly enhanced the vasopressin response (EC(50) = 2.3 nM). The synergistic effects of low-dose vasopressin and norepinephrine, or low-dose norepinephrine and vasopressin, were also significantly inhibited by 1 microM SNAP (EC(50) = 2.5 microM and 4.2 nM, respectively) or 100 microM SNAP + 10 microM IBMX (EC(50) = 9 microM and 8.4 nM, respectively).
Vasoconstriction produced by vasopressin or norepinephrine, and the synergistic vasoconstriction produced by the combinations, was inhibited in vasodilatory septic shock-like conditions. Thus, in addition to the well-described vasopressin deficiency in vasodilatory septic shock, these studies indicate that decreased vasopressin responsiveness further contributes to a state of relative vasopressin insufficiency in this condition.
Critical Care Medicine 05/2006; 34(4):1126-30. · 6.33 Impact Factor
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Beth E Taylor,
Marilyn E Schallom,
Carrie S Sona,
Timothy G Buchman, Walter A Boyle,
John E Mazuski,
Douglas E Schuerer,
James M Thomas,
Christy Kaiser,
Way Y Huey,
Myrna R Ward,
Jeanne E Zack,
Craig M Coopersmith
[show abstract]
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ABSTRACT: Hyperglycemia is associated with complications in the surgical intensive care unit. The purpose of this study was to determine the efficacy and safety of nurse-driven insulin infusion protocols in lowering blood glucose (BG) in critical illness.
All patients in a 24-bed surgical intensive care unit who required i.v. insulin infusions during 3 noncontiguous 6-month periods from 2002 to 2004 were evaluated. In the preintervention phase, 71 patients received a physician-initiated insulin infusion without a developed protocol. They were compared with 95 patients who received a nurse-driven insulin infusion protocol with a target BG of 120 to 150 mg/dL and to 119 patients who received a more stringent protocol with a target BG of 80 to 110 mg/dL.
There was a stepwise decrease in average daily BG levels, from 190 to 163 to 132 mg/dL (p < 0.001). The less stringent protocol decreased the time to achieve a BG level < 150 mg/dL from 14.1 to 7.4 hours compared with physician-driven management (p < 0.05) resulting in similar time on an insulin infusion (53 versus 48 hours). The more intensive protocol brought BG levels < 150 mg/dL in 7.2 hours and < 111 mg/dL in 13.6 hours, but increased the length of time a patient was on an insulin infusion to 77 hours. The incidence of severe hypoglycemia (BG < 40 mg/dL) was statistically similar between the groups, ranging between 1.1% and 3.4%.
Implementation of a nurse-driven protocol led to more rapid and more effective BG control in critically ill surgical patients compared with physician management. Tighter BG control can be obtained without a significant increase in hypoglycemia, although this is associated with increased time on an insulin infusion.
Journal of the American College of Surgeons 02/2006; 202(1):1-9. · 4.55 Impact Factor
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ABSTRACT: To determine the direct contractile effects of angiotensin II (AII) and vasopressin (VP), and the effects of combinations of these agonists, in human isolated gastroepiploic arteries in vitro.
Laboratory and clinical investigation.
University laboratory and hospital.
Ring segments were prepared from gastroepiploic arteries obtained from 57 patients undergoing gastrectomy. Blood samples were obtained from ten patients after severe hemorrhage and from five healthy volunteers.
Mechanical activity in the rings was assessed using a strain gauge. Plasma concentrations of AII and VP in the blood samples were measured using radioimmunoassay kits.
Both AII (1 or 10 ng/mL) and VP (100 or 500 pg/mL) produced concentration-dependent contractions in the rings. However, whereas VP produced reproducible sustained contractions, the contractile responses induced by multiple applications of AII showed marked desensitization (i.e., tachyphylaxis). Indeed, by the sixth application of either 1 ng/mL AII or 10 ng/mL AII, the contractile responses were <20% of the initial (control) response. During applications of AII after the sixth, the co-application of a low concentration of VP (100 pg/mL) fully restored the contractile response to AII in a clearly more-than-additive fashion. Similarly, the tachyphylaxis seen on AII application alone did not occur with repeated applications of an AII + norepinephrine mixture. In patients who had experienced hemorrhage, there were marked elevations of both AII and VP plasma concentrations, with values as high as 2.2 ng/mL and 550 pg/mL, respectively.
These results indicate that there is a powerful synergism between the contractile effects of low-dose VP and AII in this human isolated artery. Moreover, the elevations of plasma AII and VP levels during hemorrhage suggest that this synergism may be both physiologically and clinically important in optimizing vasoconstriction and maintaining blood pressure in such critical states.
Critical Care Medicine 12/2005; 33(11):2613-20. · 6.33 Impact Factor
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ABSTRACT: Sepsis is a potentially life-threatening medical condition induced by viral, bacterial or fungal infection, which is characterized by systemic inflammation, hypotension and vasodilation that can lead to cardiovascular collapse. Increased activity of elastases, enzymes which degrade the extracellular matrix components including elastin, has been demonstrated in plasma of septic patients. Since elastin peptides (EP), by binding to an elastin-laminin receptor on vascular endothelial and smooth muscle cells, induce dose-dependent vasodilation, we hypothesized that elevated circulating EP could contribute to the vasodilation that occurs in septic patients.
Blood for measurement of EP was collected from not-septic and septic patients admitted to the intensive care unit (ICU), as well as from healthy subjects. Plasma EP concentrations were measured using a competitive ELISA technique.
The plasma EP level in the septic patients was approximately half that of the not-septic patients and the healthy controls, with similar EP levels in the latter two groups. There was no apparent association between EP levels and age or gender in any of the groups.
Plasma EP levels were actually decreased in septic patients, possibly indicating that the balance between EP production vs. elimination favors elimination. This result further suggests that circulating EP may not be important in the development of the vasodilation and hypotension that occurs in septic shock. Alternatively, however, increased degradation of EP by elastase or other enzymes could lead to the appearance of biologically active EP, which may not be recognized by the ELISA assay.
Pathologie Biologie 10/2005; 53(7):443-7. · 1.53 Impact Factor
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Journal of Critical Care 04/2005; 20(1):114-5. · 2.13 Impact Factor
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ABSTRACT: Hypophosphatemia may cause organ derangements in the surgical intensive care unit. The purpose of this study was to determine the impact of a repletion protocol for hypophosphatemia based on admission weight and phosphorus level.
All patients who presented to an 18-bed surgical intensive care unit with a serum phosphorus level of 2.2 mg/dL or less or who received phosphorus supplementation despite having normal levels were identified. In the preintervention phase between January and June 2001, 137 patients were retrospectively identified who met these criteria. A protocol was then designed giving a single intravenous dose of phosphorus based on weight and serum phosphorus. Repletion was given with sodium or potassium phosphorus based on presupplementation levels. After protocol implementation 141 patients met these criteria between September 2001 and February 2002, and treatment and postrepletion levels were followed prospectively.
A total of 47 patients were repleted before the intervention with adequate followup and 22 (47%) attained a normal level. Supplementation success was 53% in moderate hypophosphatemia (2.2 mg/dL or less) and 27% in severe hypophosphatemia (less than 1.5 mg/dL). After protocol implementation, 111 patients were repleted with 84 (76%) correcting to a normal level (p = 0.002 compared with retrospective patients). Success was 78% in moderate hypophosphatemia and 62% in severe hypophosphatemia. Inappropriate supplementation of normal phosphorus levels decreased from 51 to 16 patients after protocol implementation.
A protocol based on weight and serum levels successfully treated both moderate and severe hypophosphatemia in the majority of critically ill patients. Protocol implementation also decreased unnecessary supplementation of normal phosphorus levels.
Journal of the American College of Surgeons 03/2004; 198(2):198-204. · 4.55 Impact Factor
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Craig M Coopersmith,
Jeanne E Zack,
Myrna R Ward,
Carrie S Sona,
Marilyn E Schallom,
Sharon J Everett,
Way Y Huey,
Teresa M Garrison,
Jan McDonald,
Timothy G Buchman, Walter A Boyle,
Victoria J Fraser,
Louis B Polish
[show abstract]
[hide abstract]
ABSTRACT: The success of an educational program in July 1999 that lowered the catheter-related bloodstream infection (CRBSI) rate in our intensive care unit (ICU) 3-fold is correlated with compliance with "best-practice" behaviors.
Before-after trial.
Surgical ICU in a referral hospital.
A random sample underwent bedside audits of central venous catheter care (n = 187). All ICU admissions during a 39-month period (N = 4489) were prospectively followed for bacteremia.
On the basis of audit results in December 2000, a behavioral intervention was designed to improve compliance with evidenced-based guidelines of central venous catheter management.
Compliance with practices known to decrease CRBSI. Secondary outcome was CRBSI rate on all ICU patients.
Multiple deficiencies were identified on bedside audits 18 months after the previous educational program. After the implementation of a separate behavioral intervention in July 2001, a second set of bedside audits in December 2001 demonstrated improvements in documenting the dressing date (11% to 21%; P<.001) and stopcock use (70% to 24%; P<.001), whereas nonsignificant trends were observed in hand hygiene (17% to 30%; P>.99) and maximal sterile barrier precautions (50% to 80%; P =.29). Appropriate practice was observed before and after the behavioral intervention in catheter site placement, dressing type, absence of antibiotic ointment, and proper securing of central venous catheters. Thirty-two CRBSIs occurred in 9353 catheter-days 24 months before the behavioral intervention compared with 17 CRBSIs in 6152 catheter-days during the 15 months after the intervention (3.4/1000 to 2.8/1000 catheter-days; P =.40).
Although a previous educational program decreased the CRBSI rate, this was associated with only modest compliance with best practice principles when bedside audits were performed 18 months later. A behavioral intervention improved all identified deficiencies, leading to a nonsignificant decrease in CRBSIs.
Archives of Surgery 03/2004; 139(2):131-6. · 4.24 Impact Factor
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Gilles Faury,
Mylène Pezet,
Russell H Knutsen, Walter A Boyle,
Scott P Heximer,
Sean E McLean,
Robert K Minkes,
Kendall J Blumer,
Attila Kovacs,
Daniel P Kelly,
Dean Y Li,
Barry Starcher,
Robert P Mecham
[show abstract]
[hide abstract]
ABSTRACT: Supravalvular aortic stenosis is an autosomal-dominant disease of elastin (Eln) insufficiency caused by loss-of-function mutations or gene deletion. Recently, we have modeled this disease in mice (Eln+/-) and found that Eln haploinsufficiency results in unexpected changes in cardiovascular hemodynamics and arterial wall structure. Eln+/- animals were found to be stably hypertensive from birth, with a mean arterial pressure 25-30 mmHg higher than their wild-type counterparts. The animals have only moderate cardiac hypertrophy and live a normal life span with no overt signs of degenerative vascular disease. Examination of arterial mechanical properties showed that the inner diameters of Eln+/- arteries were generally smaller than wild-type arteries at any given intravascular pressure. Because the Eln+/- mouse is hypertensive, however, the effective arterial working diameter is comparable to that of the normotensive wild-type animal. Physiological studies indicate a role for the renin-angiotensin system in maintaining the hypertensive state. The association of hypertension with elastin haploinsufficiency in humans and mice strongly suggests that elastin and other proteins of the elastic fiber should be considered as causal genes for essential hypertension.
Journal of Clinical Investigation 12/2003; 112(9):1419-28. · 15.39 Impact Factor
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ABSTRACT: Volatile anesthetics inhibit vascular smooth muscle contraction, but the mechanisms responsible are uncertain. In this study, the effects of halothane on Ca2+ signaling and Ca2+ activation of contractile proteins were examined in high K+-depolarized smooth muscle from rat mesenteric resistance arteries.
Vessels were cannulated and held at a constant transmural pressure (40 mmHg). Image analysis and microfluorimetry were used to simultaneously measure vessel diameter and smooth muscle intracellular [Ca2+] concentration ([Ca2+]i). Myosin light chain (MLC) phosphorylation was measured using the Western blotting technique.
Step increases in extracellular [Ca2+] concentration (0-10 mM) in high K+ (40 mM)-depolarized smooth muscle produced incremental increases in [Ca2+]i, MLC phosphorylation, and contraction. Halothane (0.5-4.5%) inhibited contraction in a concentration-dependent manner, but the decrease in [Ca2+]i was small, and there was a marked shift in the [Ca2+]i-contraction relationship to the right, indicating an important Ca2+ desensitizing effect. Halothane (0.5-4.5%) did not affect MLC phosphorylation or the [Ca2+]-MLC phosphorylation relationship, but the MLC phosphorylation-contraction relationship was also shifted rightward, indicating an "MLC phosphorylation" desensitizing effect. In contrast, control relaxations produced by the Ca2+ channel blocker nifedipine were accompanied by decreases in both [Ca2+]i and MLC phosphorylation, and nifedipine had no affect on the [Ca2+]i-contraction, [Ca2+]i-MLC phosphorylation, and MLC phosphorylation-contraction relationships.
In high K+-depolarized vascular smooth muscle, halothane relaxation is largely mediated by a Ca2+ and MLC phosphorylation desensitizing effect. These results suggest that the relaxing action of halothane is independent of the classic Ca2+-induced myosin phosphorylation contraction mechanism.
Anesthesiology 10/2003; 99(3):656-65. · 5.36 Impact Factor
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ABSTRACT: The role of calcium-independent phospholipase A(2) (iPLA(2))-produced arachidonic acid (AA) in acetylcholine (ACh)-mediated, endothelium-dependent vascular relaxation was investigated. ACh-induced relaxation of phenylephrine-constricted isolated rat mesenteric resistance arteries was attenuated following pretreatment with (E)-6-(bromomethylene)tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one (BEL; 1 microM; p < 0.01), a highly selective suicide substrate inhibitor of iPLA(2). Following BEL, the ACh relaxation could be completely restored following pretreatment with picomolar quantities of the cell-permeant methyl ester analog of AA (arachidonic acid methyl ester, AA-Me). Higher amounts of AA-Me (1 microM) had a direct endothelium-dependent relaxing action, which was inhibited by the nitric-oxide synthase inhibitor (N(omega)-nitro-L-arginine; 100 microM), independent of ACh, and unaffected by BEL. Neither the ACh relaxation restoring action nor the direct relaxing action of AA-Me was affected by preincubation with inhibitors of the lipoxygenase (esculetin, 10 microM) or cytochrome P450 monooxygenase (17-octadecynoic acid; 10 microM) pathways; and both actions of AA-Me were enhanced following preincubation with the cyclooxygenase inhibitor indomethacin (10 microM; p < 0.05). The results of the present study indicate that iPLA(2)-produced AA plays an essential role in ACh-mediated endothelium-dependent relaxation in rat mesenteric resistance arteries.
Journal of Pharmacology and Experimental Therapeutics 09/2002; 302(3):918-23. · 3.83 Impact Factor
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ABSTRACT: The actions of dexmedetomidine (DEX) on human vascular smooth muscle are unclear. We investigated its effects on isolated, endothelium-denuded human gastroepiploic arteries in vitro and compared them with clonidine (CLO). DEX had little direct effect on resting tension, whereas CLO produced small contractile responses, an effect which is blocked by the alpha(1)-adrenergic antagonist prazosin. DEX markedly enhanced the high K(+) (40 mmol/L)-induced contraction, and this effect was reversed by the alpha(2)-adrenergic antagonists yohimbine and rauwolscine but unaffected by prazosin. However, CLO had little effect on the K(+) contractions. Interestingly, larger concentrations (>10(-7) mol/L) of both alpha(2)-adrenergic stimulants significantly inhibited the contractions elicited by the alpha(1)-adrenergic agonist phenylephrine (10(-6) mol/L) and, to a lesser extent, those elicited by the alpha(1)/alpha(2)-agonist norepinephrine (10(-6) mol/L). These results suggest the possibility that DEX and CLO each have a high affinity for alpha(1)-adrenoceptors in human isolated gastroepiploic arteries, resulting in a reduced efficacy of alpha(1)-adrenergic activation by alpha-agonists. The differing affinities of the drugs for alpha(1)- and alpha(2)-adrenoceptors may help explain their additional actions: 1) DEX enhances the high K(+)-induced contraction presumably through alpha(2)-adrenoceptor activation, and 2) CLO acts on alpha(1)-adrenoceptors as a partial agonist when present alone. IMPLICATIONS: Dexmedetomidine may not directly affect smooth muscle in human peripheral resistance vessels within the usual range of plasma concentrations (<10(-7) mol/L) achieved in clinical practice. However, in large doses, it could enhance the response to nonadrenergic vasoconstrictor agonists while antagonizing the vasoconstrictor response to alpha(1)-adrenoceptor agonists.
Anesthesia & Analgesia 07/2002; 94(6):1434-40, table of contents. · 3.29 Impact Factor
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Craig M Coopersmith,
Terri L Rebmann,
Jeanne E Zack,
Myrna R Ward,
Roslyn M Corcoran,
Marilyn E Schallom,
Carrie S Sona,
Timothy G Buchman, Walter A Boyle,
Louis B Polish,
Victoria J Fraser
[show abstract]
[hide abstract]
ABSTRACT: The purpose of the study was to determine whether an education initiative aimed at improving central venous catheter insertion and care could decrease the rate of primary bloodstream infections.
Pre- and postintervention observational study.
Eighteen-bed surgical/burn/trauma intensive care unit (ICU) in an urban teaching hospital.
A total of 4,283 patients were admitted to the ICU between January 1, 1998, and December 31, 2000.
A program primarily directed toward registered nurses was developed by a multidisciplinary task force to highlight correct practice for central venous catheter insertion and maintenance. The program consisted of a 10-page self-study module on risk factors and practice modifications involved in catheter-related infections as well as a verbal in-service at staff meetings. Each participant was required to take a pretest before taking the study module and an identical test after its completion. Fact sheets and posters reinforcing the information in the study module were also posted throughout the ICU.
Seventy-four primary bloodstream infections occurred in 6874 catheter days (10.8 per 1000 catheter days) in the 18 months before the intervention. After the implementation of the education module, the number of primary bloodstream infections fell to 26 in 7044 catheter days (3.7 per 1000 catheter days), a decrease of 66% (p < .0001). The estimated cost savings secondary to the decreased infection rate for the 18 months after the intervention was between $185,000 and $2.808 million.
A focused intervention primarily directed at the ICU nursing staff can lead to a dramatic decrease in the incidence of primary bloodstream infections. Educational programs may lead to a substantial decrease in cost, morbidity, and mortality attributable to central venous catheterization.
Critical Care Medicine 02/2002; 30(1):59-64. · 6.33 Impact Factor
