Biomedical subjects

Janice L Zimmerman

Publications and source records attributed to Janice L Zimmerman.

7 recordsLinked to original sources

PubMed2006

The role of intrinsic efficacy in determining response to a beta2-agonist in acute severe asthma.

BACKGROUND: Current guidelines recommend repeated doses of albuterol for the emergency treatment of acute asthma. However, approximately one-third of patients show little or no initial response to this partial beta(2)-agonist. METHODS: We conducted a randomized, double-blind, proof-of-concept study to investigate whether a full beta(2)-agonist, isoproterenol, offers a therapeutic advantage in adults presenting with acute severe asthma (FEV(1)<50%) who fail to respond to an initial treatment of the partial beta(2)-agonist, albuterol. Study subjects were randomized to receive a 2-h continuous nebulization of either albuterol (7.5mg/h) (n=10, mean FEV(1)=37% predicted) or isoproterenol (7.5mg/h) (n=9, mean FEV(1)=33% predicted). Respiratory symptoms, vital signs and pulmonary function measures were collected. RESULTS: Subjects from both treatment groups had similar baseline characteristics. The percent improvements from baseline FEV(1) at 60 and 120min were significantly higher in subjects receiving isoproterenol than those receiving albuterol (44 vs. 17% and 63 vs. 24%, respectively, P<0.05). The change in symptoms measured by the modified Borg score was also significantly greater in subjects receiving isoproterenol (P<0.01). Both treatments were well tolerated, though the mean increase in pulse rate at 60 and 120min (21 vs. 1 and 23 vs. 6beats/min, respectively, P<0.05) and the mean change in serum potassium at 120min (-0.52 vs. -0.07meq/L, P<0.05) from baseline were significantly greater in the isoproterenol group. CONCLUSIONS: Our data suggest that in subjects presenting with acute severe asthma who fail to show an initial response to albuterol, the use of a beta(2)-agonist of higher intrinsic efficacy can be more effective in improving lung function and symptoms.

Acute Disease↗

PubMed2004

Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial.

CONTEXT: Inhaled nitric oxide has been shown to improve oxygenation in acute lung injury. OBJECTIVE: To evaluate the clinical efficacy of low-dose (5-ppm) inhaled nitric oxide in patients with acute lung injury. DESIGN AND SETTING: Multicenter, randomized, placebo-controlled study, with blinding of patients, caregivers, data collectors, assessors of outcomes, and data analysts (triple blind), conducted in the intensive care units of 46 hospitals in the United States. Patients were enrolled between March 1996 and September 1999. PATIENTS: Patients (n = 385) with moderately severe acute lung injury, a modification of the American-European Consensus Conference definition of acute respiratory distress syndrome (ARDS) using a ratio of PaO2 to FiO2 of < or =250, were enrolled if the onset was within 72 hours of randomization, sepsis was not the cause of the lung injury, and the patient had no significant nonpulmonary organ system dysfunction at randomization. INTERVENTIONS: Patients were randomly assigned to placebo (nitrogen gas) or inhaled nitric oxide at 5 ppm until 28 days, discontinuation of assisted breathing, or death. MAIN OUTCOME MEASURES: The primary end point was days alive and off assisted breathing. Secondary outcomes included mortality, days alive and meeting oxygenation criteria for extubation, and days patients were alive following a successful unassisted ventilation test. RESULTS: An intent-to-treat analysis revealed that inhaled nitric oxide at 5 ppm did not increase the number of days patients were alive and off assisted breathing (mean [SD], 10.6 [9.8] days in the placebo group and 10.7 [9.7] days in the inhaled nitric oxide group; P =.97; difference, -0.1 day [95% confidence interval, -2.0 to 1.9 days]). This lack of effect on clinical outcomes was seen despite a statistically significant increase in PaO2 that resolved by 48 hours. Mortality was similar between groups (20% placebo vs 23% nitric oxide; P =.54). Days patients were alive following a successful 2-hour unassisted ventilation trial were a mean (SD) of 11.9 (9.9) for placebo and 11.4 (9.8) for nitric oxide patients (P =.54). Days alive and meeting criteria for extubation were also similar: 17.0 placebo vs 16.7 nitric oxide (P =.89). CONCLUSION: Inhaled nitric oxide at a dose of 5 ppm in patients with acute lung injury not due to sepsis and without evidence of nonpulmonary organ system dysfunction results in short-term oxygenation improvements but has no substantial impact on the duration of ventilatory support or mortality.

Administration, Inhalation↗

PubMed2004

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.

OBJECTIVE: To develop management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. The modified Delphi methodology used for grading recommendations built upon a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along 5 levels to create recommendation grades from A-E, with A being the highest grade. Pediatric considerations were provided to contrast adult and pediatric management. PARTICIPANTS: Participants included 44 critical care and infectious disease experts representing 11 international organizations. RESULTS: A total of 46 recommendations plus pediatric management considerations. CONCLUSIONS: Evidence-based recommendations can be made regarding many aspects of the acute management of sepsis and septic shock that will hopefully translate into improved outcomes for the critically ill patient. The impact of these guidelines will be formally tested and guidelines updated annually, and even more rapidly when some important new knowledge becomes available.

Adult↗

PubMed2004

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: We used a modified Delphi methodology for grading recommendations, built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations were provided to contrast adult and pediatric management. RESULTS: Key recommendations, listed by category and not by hierarchy, include early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition; appropriate diagnostic studies to ascertain causative organisms before starting antibiotics; early administration of broad-spectrum antibiotic therapy; reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate; a usual 7-10 days of antibiotic therapy guided by clinical response; source control with attention to the method that balances risks and benefits; equivalence of crystalloid and colloid resuscitation; aggressive fluid challenge to restore mean circulating filling pressure; vasopressor preference for norepinephrine and dopamine; cautious use of vasopressin pending further studies; avoiding low-dose dopamine administration for renal protection; consideration of dobutamine inotropic therapy in some clinical situations; avoidance of supranormal oxygen delivery as a goal of therapy; stress-dose steroid therapy for septic shock; use of recombinant activated protein C in patients with severe sepsis and high risk for death; with resolution of tissue hypoperfusion and in the absence of coronary artery disease or acute hemorrhage, targeting a hemoglobin of 7-9 g/dL; appropriate use of fresh frozen plasma and platelets; a low tidal volume and limitation of inspiratory plateau pressure strategy for acute lung injury and acute respiratory distress syndrome; application of a minimal amount of positive end-expiratory pressure in acute lung injury/acute respiratory distress syndrome; a semirecumbent bed position unless contraindicated; protocols for weaning and sedation/analgesia, using either intermittent bolus sedation or continuous infusion sedation with daily interruptions/lightening; avoidance of neuromuscular blockers, if at all possible; maintenance of blood glucose <150 mg/dL after initial stabilization; equivalence of continuous veno-veno hemofiltration and intermittent hemodialysis; lack of utility of bicarbonate use for pH > or =7.15; use of deep vein thrombosis/stress ulcer prophylaxis; and consideration of limitation of support where appropriate. Pediatric considerations included a more likely need for intubation due to low functional residual capacity; more difficult intravenous access; fluid resuscitation based on weight with 40-60 mL/kg or higher needed; decreased cardiac output and increased systemic vascular resistance as the most common hemodynamic profile; greater use of physical examination therapeutic end points; unsettled issue of high-dose steroids for therapy of septic shock; and greater risk of hypoglycemia with aggressive glucose control. CONCLUSION: Evidence-based recommendations can be made regarding many aspects of the acute management of sepsis and septic shock that are hoped to translate into improved outcomes for the critically ill patient. The impact of these guidelines will be formally tested and guidelines updated annually and even more rapidly as some important new knowledge becomes as available.

Adult↗

PubMed2004

Use of blood products in sepsis: an evidence-based review.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for the use of blood products in sepsis that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and to improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591. CONCLUSION: In the absence of extenuating circumstances and following resolution of tissue hypoperfusion, red blood cell transfusion should be targeted to maintain hemoglobin at 7.0 g/dL or greater. Erythropoietin is not recommended as a specific treatment for sepsis-associated anemia. Fresh-frozen plasma should be given for documented deficiency of coagulation factors and in the presence of active bleeding or before surgical or invasive procedures. Antithrombin administration is not recommended. Specific platelet transfusion thresholds are based on the presence or absence of bleeding, significant risk for bleeding, plans for surgery or invasive procedures, and platelet count </=5,000/mm.

Antithrombins↗

PubMed2003

Poisonings and overdoses in the intensive care unit: general and specific management issues.

OBJECTIVE: To provide current information on general and specific interventions for overdoses likely to require intensive care. DESIGN: Review of literature relevant to selected interventions for general management of overdoses and specific poisons. RESULTS: The benefit of interventions to decrease absorption or enhance elimination of toxins is limited to a relatively small number of specific agents. Antidotes and certain interventions may be helpful in preventing or treating toxicity in specific poisonings when used appropriately. Intensive supportive care is also necessary to achieve good outcomes. CONCLUSION: Knowledge of the indications and limitations of current interventions for poisonings and overdoses is important for care of the critically ill poisoned patient.

Adrenergic beta-Antagonists↗

PubMed2002

Respiratory failure.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common causes of hypoxemic respiratory failure. Multiple etiologies lead to direct and indirect pulmonary injury that progresses through an acute exudative phase, fibroproliferative phase, and recovery phase. Inflammatory mechanisms are thought to play a predominant role in the pathophysiology of ALI/ARDS. Mechanical ventilation with a lower tidal volume and an inspiratory plateau pressure of < or = 30 cm H2O is one intervention that has demonstrated a reduction in mortality. A clinical trial to determine the role of restrictive versus liberal fluid management is underway. Inhaled nitric oxide has been used to improve oxygenation but has not resulted in any outcome benefit. Glucocorticoids may be beneficial in the fibroproliferative phase of lung injury by suppressing chronic inflammation. Rigorous clinical trials of new and established interventions are required to determine optimum therapy and reduce mortality in ALI/ARDS.

Adult↗