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Jonathan E Sevransky

Publications and source records attributed to Jonathan E Sevransky.

5 recordsLinked to original sources

Preclinical trial of L-arginine monotherapy alone or with N-acetylcysteine in septic shock.

OBJECTIVE: L-arginine supplementation in sepsis is controversial. Septic shock has been alternatively viewed as an L-arginine-deficient state or as a syndrome caused by excess nitric oxide, an end-product of L-arginine metabolism. DESIGN: Randomized, placebo-controlled, and double-blinded (investigators, veterinarians, and pharmacists). SETTING: Laboratory. SUBJECTS: Purpose-bred, 1- to 2-yr-old, 10- to 12-kg beagles. INTERVENTIONS: The effects of parenteral L-arginine alone or in combination with N-acetylcysteine were compared with vehicle alone in a well-characterized canine model of Escherichia coli peritonitis. Two doses were studied that delivered approximately 1.5-fold (10 mg x kg(-1) x hr(-1)) and 15-fold (100 mg x kg(-1) x hr(-1)) the L-arginine dose typically administered with standard total parenteral nutrition. Animals in the low- and high-dose L-arginine arms were further randomized to receive vehicle alone or N-acetylcysteine (20 mg x kg(-1) x hr(-1)) as an antioxidant to prevent peroxynitrite formation. MEASUREMENTS AND MAIN RESULTS: The main measurements were hemodynamics, plasma arginine and ornithine, serum nitrate/nitrite, laboratory studies for organ injury, and survival. Both doses of L-arginine similarly increased mortality (p = .02), and worsened shock (p = .001 for reduced mean arterial pressure). These effects were associated with significant increases in plasma arginine (p = .0013) and ornithine (p = .0021). In addition, serum nitrate/nitrite (p = .02), liver enzymes (p = .08), and blood urea nitrogen/creatinine ratios (p = .001) rose, whereas arterial pH (p = .001) and bicarbonate levels (p = .001) fell. N-acetylcysteine did not significantly decrease any of the harmful effects of L-arginine. Thus, parenteral L-arginine monotherapy was markedly harmful in animals with septic shock. CONCLUSIONS: These findings suggest that supplemental parenteral L-arginine, at doses above standard dietary practices, should be avoided in critically ill patients with septic shock.

Acetylcysteine↗

Mechanical ventilation in sepsis-induced acute lung injury/acute respiratory distress syndrome: an evidence-based review.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for mechanical ventilation in sepsis-induced acute lung injury/acute respiratory distress syndrome (ARDS) 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: 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: A minimum amount of positive end-expiratory pressure should be set to prevent lung collapse at end expiration in ARDS. Setting the level of positive end-expiratory pressure may be guided by Fio2 requirement or measurement of thoracopulmonary compliance. Role of noninvasive positive-pressure ventilation in acute lung injury/ARDS is undefined. Small tidal volume ventilation and limitation of end-inspiratory plateau pressure is important in the management of ARDS and may be facilitated by permissive hypercapnia. Prone positioning should be considered in the severest of ARDS patients. The ideal fluid management strategy in ARDS is unknown. Weaning protocols should be in place that include spontaneous breathing trials and criteria for initiating such trials. The role of high-frequency oscillatory ventilation and airway pressure release ventilation in ARDS is uncertain.

Administration, Inhalation↗

Granulocyte colony-stimulating factor has differing effects comparing intravascular versus extravascular models of sepsis.

BACKGROUND: Previously, neutrophil stimulation with granulocyte colony-stimulating factor (G-CSF) pretreatment increased survival rates in canines challenged with intraperitoneal or intrabronchial Escherichia coli and in rats challenged with intrabronchial Staphylococcus aureus. We investigated whether G-CSF pretreatment would be beneficial with intravascular challenge in these models. METHODS: Animals were randomized to G-CSF or placebo pretreatment followed by intravenous E. coli challenge in canines (n = 24) or intravenous or intrabronchial S. aureus challenge in rats (n = 273). All animals were treated with antibiotics. RESULTS: In canines, G-CSF before intravenous E. coli did not decrease mortality rates (7 of 12 [58%] G-CSF vs. 5 of 12 [42%] controls), which contrasted with prior reductions during extravascular infection (10 of 35 [29%] G-CSF vs. 37 of 65 [57%] controls). Consistent with the present and previously published studies in canines, in rats, G-CSF decreased mortality rates with intrabronchial S. aureus (22 of 90 [24%] G-CSF vs. 26 of 51 [51%] controls, p = 0.009) but did not decrease them with intravenous infection (34 of 67 [50%] G-CSF vs. 27 of 65 [42%] controls, p = 0.2) in patterns that were very different (p = 0.005 for the effects of G-CSF with intravascular vs. intrabronchial S. aureus). CONCLUSION: In contrast to extravascular infection, sepsis with intravascular E. coli in canines and S. aureus in rats may not provide a compartmentalized nidus of bacteria on which G-CSF-stimulated neutrophils can exert a beneficial antimicrobial effect. Extrapolated clinically, a proinflammatory agent like G-CSF may be most beneficial with sepsis related primarily to a compartmentalized extravascular site of infection.

Animals↗

Respiratory failure in elderly patients.

Elderly individuals comprise an increasing proportion of the population and represent a progressively expanding number of patients admitted to the ICU. Because of underlying pulmonary disease, loss of muscle mass, and other comorbid conditions, older persons are at increased risk of developing respiratory failure. Recognition of this vulnerability and the adoption of proactive measures to prevent decompensation requiring intrusive support are major priorities together with clear delineation of patients' wishes regarding the extent of support desired should clinical deterioration occur. Further, the development of coordinated approaches to identify patients at risk for respiratory failure and strategies to prevent the need for intubation, such as the use of NIV in appropriate patients, are crucial. As soon as endotracheal intubation and mechanical ventilation are implemented strategies that facilitate the liberation of elderly patients from the ventilator are especially important. The emphasis on a team approach, which characterizes geriatric medicine, is essential in coordinating the skills of multiple health care professionals in this setting. Respiratory failure can neither be effectively diagnosed nor managed in isolation. Integration with all other aspects of care is essential. Patient vulnerability to nosocomial complications and the "cascade effect" of these problems such as the effects of medications and invasive supportive procedures all impact on respiratory care of elderly patients. For example, prolonged mechanical ventilation may be required long after resolution of the underlying cause of respiratory failure because of unrecognized and untreated delirium or residual effects of small doses of sedative and/or analgesic agents or other medications in elderly patients with altered drug metabolism. The deleterious impact of the foreign and sometimes threatening ICU environment and/or sleep deprivation on the patient's course are too often overlooked because the physician focuses management on physiologic measurements, mechanical ventilator settings, and other technologic nuances of care [40]. Review of the literature suggests that the development of respiratory failure in patients with certain disease processes such as COPD, IPF, and ARDS in elderly patients may lead to worsened outcome but it appears that the disease process itself, rather than the age of the patient, is the major determinant of outcome. Additional studies suggest that other comorbid factors may be more important than age. Only when comorbid processes are taken into account should decisions be made about the efficacy of instituting mechanical ventilation. In addition, because outcome prediction appears to be more accurate for groups of patients rather than for individual patients a well-structured therapeutic trial of instituting mechanical ventilation, even if comorbidities are present, may be indicated in certain patients if appropriately informed patients wish to pursue this course. This approach requires careful and realistic definition of potential outcomes, focus on optimizing treatment of the reversible components of the illness, and continuous communication with the patient and family. Although many clinicians share a nihilistic view regarding the potential usefulness of mechanical ventilation in elderly patients few data warrant this negative prognostication and more outcome studies are needed to delineate the optimum application of this element of supportive care. As with other interventions individualization of the decision must take into account the patient's premorbid status, concomitant conditions, the nature of the precipitating illness and its prospects for improvement, and most important, patient preferences. In this determination pursuing the course most consistent with the patient's wishes is essential and it must be appreciated that caregivers' impressions regarding the vigor of support desired by the patient are often erroneous. The SUPPORT investigators observed that clinicians often underestimated the degree of intervention desired by older patients assuming that less care would be desired [13]. Thus, as in other circumstances, effective communication and elicitation of patients' preferences regarding management options is crucial in the management of respiratory failure. The frequent discordance between patient preferences and the wishes of family members or other surrogate decision makers impose major clinical challenges and also mandates further investigation.

Age Factors↗