Objective:To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008.Design:A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at ke

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

The discovery that mammalian cells generate nitric oxide, a gas previously considered to be merely an atmospheric pollutant, is providing important information about many biologic processes. Nitric oxide is synthesized from the amino acid L-arginine by a family of enzymes, the nitric oxide synthases, through a hitherto unrecognized metabolic route -- namely, the L-arginine-nitric oxide pathway1–8. The synthesis of nitric oxide by vascular endothelium is responsible for the vasodilator tone that is essential for the regulation of blood pressure. In the central nervous system nitric oxide is a neurotransmitter that underpins several functions, including the formation of memory. . . .

The L-Arginine-Nitric Oxide Pathway

To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7–9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a Pao
 2/Fio
 2 ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a Pao
 2/Fi
 o
 2 180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5–10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven “absolute”’ adrenal insufficiency (2C). Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

/pdf/surviving-sepsis-campaign-international-guidelines-for-229kg8suph.pdf

Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012

The acute respiratory distress syndrome is a common, devastating clinical syndrome of acute lung injury that affects both medical and surgical patients. Since the last review of this syndrome appeared in the Journal, 1 more uniform definitions have been devised and important advances have occurred in the understanding of the epidemiology, natural history, and pathogenesis of the disease, leading to the design and testing of new treatment strategies. This article provides an overview of the definitions, clinical features, and epidemiology of the acute respiratory distress syndrome and discusses advances in the areas of pathogenesis, resolution, and treatment. Historical Perspective and Definitions . . .

/pdf/the-acute-respiratory-distress-syndrome-4dksnctehq.pdf

The acute respiratory distress syndrome

To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012”. A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

https://link.springer.com/content/pdf/10.1007%2Fs00134-017-4683-6.pdf

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

Efficacy of inhaled nitric oxide in patients with severe ARDS.

Objective
To evaluate the lowest dose of inhaled nitric oxide (NO) in patients with adult respiratory distress syndrome (ARDS), which is able to improve arterial oxygenation more than 30% compared to baseline data.

/pdf/long-term-inhalation-with-evaluated-low-doses-of-nitric-gbm1uju2jg.pdf

Long-term inhalation with evaluated low doses of nitric oxide for selective improvement of oxygenation in patients with adult respiratory distress syndrome

An exaggerated hypoxic pulmonary vasoconstriction is essential for development of high-altitude pulmonary edema (HAPE). We hypothesized that susceptibility to HAPE may be related to decreased production of nitric oxide (NO), an endogenous modulator of pulmonary vascular resistance, and that a decrease in exhaled NO could be detected during hypoxic exposure. Therefore, we investigated respiratory tract NO excretion by chemiluminescence and pulmonary artery systolic pressure (Ppa,s) by echocardiography in nine HAPE-susceptible mountaineers and nine HAPE-resistant control subjects during normoxia and acute hypoxia (fraction of inspired oxygen [FI(O2)] = 0.12). The subjects performed oral breathing. Nasally excreted NO was separated from respiratory gas by suction via a nasal mask. In HAPE-susceptible subjects, NO excretion in expired gas significantly decreased (p < 0.05) during hypoxia of 2 h in comparison with normoxia (28 +/- 4 versus 21 +/- 2 nl/min, mean +/- SEM). In contrast, the NO excretion rate of control subjects remained unchanged (31 +/- 6 versus 33 +/- 6 nl/ min, NS). Nasal NO excretion did not differ significantly between groups during normoxia (HAPE-susceptible group, 183 +/- 16 nl/ min; control subjects, 297 +/- 55 nl/min, NS) and was not influenced by hypoxia. The changes in Ppa,s with hypoxia correlated with the percent changes in lower respiratory tract NO excretion (R = -0.49, p = 0.04). Our data provide the first evidence of decreased pulmonary NO production in HAPE-susceptible subjects during acute hypoxia that may contribute among other factors to their enhanced hypoxic pulmonary vascular response.

https://www.atsjournals.org/doi/pdf/10.1164/ajrccm.163.2.2001134

Hypoxia decreases exhaled nitric oxide in mountaineers susceptible to high-altitude pulmonary edema.

A prospective multicenter study was carried out from October 1 to November 30, 1991, to determine the incidence, severity, and mortality of acute respiratory failure (ARF) in Berlin, Germany, a metropolis with a population of 3.44 million. Adult patients from 72 intensive care units (ICUs) were evaluated. ARF was defined as: (1) intubation and mechanical ventilation (I+MV) > or = 24 h; age > or = 14 yr. Incidence of ARF was assessed as the number of patients fulfilling ARF criteria within the 2-mo study period. Severity of ARF was defined as "no lung injury" (NLI), "mild-to-moderate lung injury" (MMLI), and "severe lung injury" (SLI) according to Murray and coworkers' proposals. Mortality was assessed as number of patients with ARF dying during ICU stay. During the study period, 508 patients were diagnosed as having ARF, representing an incidence of ARF of 88.6 per 100,000/yr. Twenty-four h after I+MV, MMLI occurred in 94% and SLI in 3.6% of the ARF patients. Overall mortality rate was 42.7%. Mortality rate in the NLI group was 36.4%; in patients with MMLI, 40.8%; and in patients with SLI, 58.8%. Our data offer novel information on incidence, severity, and mortality of ARF in a major urban population.

Incidence, severity, and mortality of acute respiratory failure in Berlin, Germany.

Inhaled nitric oxide (NO) improves systemic oxygenation (PaO2/FIO2) in adult patients with acute respiratory distress syndrome (ARDS). However, individual response varies, and previous trials demonstrated no outcome benefit. This prospective, randomized study in 40 ARDS patients analyzed dose–response (DR) characteristics during long-term inhaled NO. Patients were randomized for conventional therapy (control) or continuous treatment with 10 parts per million (ppm) inhaled NO until weaning was initiated. We measured DR curves of PaO2/FIO2 versus the inhaled NO dose at regular intervals. Before treatment (Day 0), peak improvement in PaO2/FIO2 was achieved at 10 ppm for both control and NO-treated patients. After 4 days, the DR curve of the NO-treated patients was left shifted with a peak response at 1 ppm. At higher doses (10 and 100 ppm), oxygenation deteriorated, and the response to inhaled NO disappeared in several patients. This effect was not observed in the control group. There was no effect of inhale...

https://www.atsjournals.org/doi/pdf/10.1164/rccm.2108121

Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome: a prospective, randomized, controlled study.

Konrad J. Falke

Papers

Efficacy of inhaled nitric oxide in patients with severe ARDS.

Long-term inhalation with evaluated low doses of nitric oxide for selective improvement of oxygenation in patients with adult respiratory distress syndrome

Hypoxia decreases exhaled nitric oxide in mountaineers susceptible to high-altitude pulmonary edema.

Incidence, severity, and mortality of acute respiratory failure in Berlin, Germany.

Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome: a prospective, randomized, controlled study.