Search

Objective:To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012.”Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for

OBJECTIVE: Sepsis is associated with high early and total in-hospital mortality. Despite recent revisions in the diagnostic criteria for sepsis that sought to improve predictive validity for mortality, it remains difficult to identify patients at greatest risk of death. We compared the utility of nine biomarkers to predict mortality in subjects with clinically suspected bacterial sepsis. DESIGN: Cohort study. SETTING: The medical and surgical intensive care units at an academic medical center. SUBJECTS: We enrolled 139 subjects who met two or more systemic inflammatory response syndrome (SIRS) criteria and received new broad-spectrum antibacterial therapy. INTERVENTIONS: We assayed nine biomarkers (α-2 macroglobulin, C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin, serum amyloid A, serum amyloid P [SAP], and tissue plasminogen activator [TPA]) at onset of suspected sepsis and 24-, 48-, and 72-hours thereafter. We compared biomarkers between groups based on both 14-day and total in-hospital mortality and evaluated the predictive validity of single and paired biomarkers via area under the receiver operating characteristic curve (AUROC). MEASUREMENTS AND MAIN RESULTS: 14-day mortality was 12.9%, and total in-hospital mortality was 29.5%. SAP was significantly lower (4 of 4 timepoints) and TPA significantly higher (3 of 4 timepoints) in the 14-day mortality group, and the same pattern held for total in-hospital mortality (Wilcoxon p

Treatment with inhaled nitric oxide improves oxygenation but not survival in mechanically ventilated patients with acute respiratory distress syndrome, but the effect may depend on the severity of hypoxemia. Our objective was to determine whether nitric oxide reduces hospital mortality in patients with severe acute respiratory distress syndrome (PaO2/FIO2 ≤ 100 mm Hg) but not in patients with mild-moderate acute respiratory distress syndrome (100PaO2/FIO2 ≤ 300 mm Hg) at the time of randomization.Data were collected from Medline, Embase, and Cochrane CENTRAL electronic databases (inception to May 2013); proceedings from five conferences (to May 2013); and trial registries (http://www.clinicaltrials.gov and http://www.controlled-trials.com). No language restrictions were applied.Two authors independently selected parallel-group randomized controlled trials comparing nitric oxide with control (placebo or no gas) in mechanically ventilated adults or postneonatal children with acute respiratory distress syndrome.Two authors independently extracted data from included trials. Trial investigators provided subgroup data. Meta-analyses used within-trial subgroups and random-effects models.Nine trials (n = 1,142 patients) met inclusion criteria. Overall methodological quality was good. Nitric oxide did not reduce mortality in patients with severe acute respiratory distress syndrome (risk ratio, 1.01 [95% CI, 0.78-1.32]; p = 0.93; n = 329, six trials) or mild-moderate acute respiratory distress syndrome (risk ratio, 1.12 [95% CI, 0.89-1.42]; p = 0.33; n = 740, seven trials). Risk ratios were similar between subgroups (interaction p = 0.53). There was no between-trial heterogeneity in any analysis (I = 0%). Varying the PaO2/FIO2 threshold between 70 and 200 mm Hg, in increments of 10 mm Hg, did not identify any threshold at which the nitric oxide-treated patients had lower mortality relative to controls.Nitric oxide does not reduce mortality in adults or children with acute respiratory distress syndrome, regardless of the degree of hypoxemia. Given the lack of related ongoing or recently completed randomized trials, new data addressing the effectiveness of nitric oxide in patients with acute respiratory distress syndrome and severe hypoxemia will not be available for the foreseeable future.

Background:Patients with sepsis syndrome commonly have low serum selenium levels. Several randomized controlled trials have examined the efficacy of selenium supplementation on mortality in patients with sepsis.Objective:To determine the efficacy and safety of high-dose selenium supplementation comp

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

The Surviving Sepsis Campaign developed guidelines for the administration of recombinant human activated protein C in adult severe sepsis. However, it is not clear how these impacted clinical practice or patient outcome.The Surviving Sepsis Campaign has developed an extensive database to assess the efficacy of the overall effect of its guidelines on clinical practice and patient outcome. From data submitted to the Surviving Sepsis Campaign database from January 2005 through March 2008, we evaluated data regarding the administration of recombinant human activated protein C in adult severe sepsis.Data from 15,022 subjects at 165 sites were analyzed.Of patients with severe sepsis in the database, 1,009 of 15,022 (8%) received recombinant human activated protein C. Recombinant human activated protein C was administered within 24 hrs of the onset of sepsis in 76% (771 of 1009) of patients. Patients in North America (7.1%) and Europe (6.8%) were more likely to receive recombinant human activated protein C than patients in South America (4.2%, p.001). After adjusting for covariates, the group that received recombinant human activated protein C had a significantly reduced associated hospital mortality (odds ratio 0.76, 95% confidence interval 0.66-0.86, p.001). Comparing all the patients who received recombinant human activated protein C to those who did not receive recombinant human activated protein C, the reduction in the adjusted hospital mortality was only statistically significant in patients who had multiorgan dysfunction (odds ratio 0.82, 95% confidence interval 0.69-0.98, p=.027) vs. those who only had single organ dysfunction (odds ratio 0.78, 95% confidence interval 0.59-1.02, p=.072). However, in patients who received recombinant human activated protein C before 24 hrs there was a reduction in adjusted hospital mortality in patients with only one organ dysfunction (odds ratio 0.70, 95% confidence interval 0.51-0.9, p=.03) as well as patients with multiorgan dysfunction (odds ratio 0.78, 95% confidence interval 0.64-0.94 p=.012). There was a statistically significant increase over time in the percentage compliance with the institution of a recombinant human activated protein C administration policy from the first, second, and eighth quarters (47.4%, 46.2%, and 60.7%, respectively) (p.001). There was also a statistically significant increase in the actual administration rates of recombinant human activated protein C over the same timeline (p.001), with administration rates of recombinant human activated protein C reaching 9.2% in the last quarter.Recombinant human activated protein C use was associated with a significant improvement in hospital mortality in patients who participated in the Surviving Sepsis Campaign.

Up-regulated matrix metalloproteinases may be involved in the development of cardiomyocyte injury and the degradation of troponin associated with acute pulmonary thromboembolism. We examined whether pretreatment with doxycycline (a nonspecific matrix metalloproteinase inhibitor) protects against cardiomyocyte injury associated with acute pulmonary thromboembolism.Controlled animal study.University research laboratory.Mongrel dogs.Anesthetized animals received doxycycline (10 mg/kg intravenously) or saline and acute pulmonary thromboembolism was induced with autologous blood clots injected into the right atrium. Control animals received doxycycline (or saline).Hemodynamic measurements were performed, and acute pulmonary thromboembolism increased baseline mean pulmonary arterial pressure and pulmonary vascular resistance by approximately 160% and 362%, respectively (both p.05), 120 mins after acute pulmonary thromboembolism. Pretreatment with doxycycline attenuated these increases (to 125% and 232%, respectively; both p.05). Although acute pulmonary thromboembolism tended to increase the right ventricle maximum rate of isovolumic pressure development and the maximum rate of isovolumic pressure decay, doxycycline produced no effects on these parameters. Gelatin zymograms of right ventricle showed that acute pulmonary thromboembolism marginally increased matrix metalloproteinase-9 (but not matrix metalloproteinase-2) levels in the right ventricle. A fluorometric assay to assess net matrix metalloproteinase activities showed that acute pulmonary thromboembolism increased matrix metalloproteinase activities in the right ventricle by100% (p.05), and this finding was confirmed by in situ zymography of the right ventricle. Doxycycline attenuated acute pulmonary thromboembolism-induced increases in right ventricle matrix metalloproteinase activities. Acute pulmonary thromboembolism induced neutrophil accumulation in the right ventricle, as estimated by myeloperoxidase activity, and doxycycline blunted this effect (p.05). Serum cardiac troponin I concentrations, which reflect cardiomyocyte injury, increased after acute pulmonary thromboembolism, and this increase was attenuated by pretreatment with doxycycline (p.05).We found evidence supporting the idea that acute pulmonary thromboembolism is associated with increased matrix metalloproteinase activities in the right ventricle, which may lead to degradation of sarcomeric proteins, including cardiac troponin I. Inhibition of matrix metalloproteinases may be an effective therapeutic intervention in the management of acute pulmonary thromboembolism.

To simultaneously determine perceived vs. practiced adherence to recommended interventions for the treatment of severe sepsis or septic shock.One-day cross-sectional survey.Representative sample of German intensive care units stratified by hospital size.Adult patients with severe sepsis or septic shock.None.Practice recommendations were selected by German Sepsis Competence Network (SepNet) investigators. External intensivists visited intensive care units randomly chosen and asked the responsible intensive care unit director how often these recommendations were used. Responses "always" and "frequently" were combined to depict perceived adherence. Thereafter patient files were audited. Three hundred sixty-six patients on 214 intensive care units fulfilled the criteria and received full support. One hundred fifty-two patients had acute lung injury or acute respiratory distress syndrome. Low-tidal volume ventilationor = 6 mL/kg/predicted body weight was documented in 2.6% of these patients. A total of 17.1% patients had tidal volume between 6 and 8 mL/kg predicted body weight and 80.3%8 mL/kg predicted body weight. Mean tidal volume was 10.0 +/- 2.4 mL/kg predicted body weight. Perceived adherence to low-tidal volume ventilation was 79.9%. Euglycemia (4.4-6.1 mmol/L) was documented in 6.2% of 355 patients. A total of 33.8% of patients had blood glucose levelsor = 8.3 mmol/L and 66.2% were hyperglycemic (blood glucose8.3 mmol/L). Among 207 patients receiving insulin therapy, 1.9% were euglycemic, 20.8% had blood glucose levelsor = 8.3 mmol/L, and 1.0% were hypoglycemic. Overall, mean maximal glucose level was 10.0 +/- 3.6 mmol/L. Perceived adherence to strict glycemic control was 65.9%. Although perceived adherence to recommendations was higher in academic and larger hospitals, actual practice was not significantly influenced by hospital size or university affiliation.This representative survey shows that current therapy of severe sepsis in German intensive care units complies poorly with practice recommendations. Intensive care unit directors perceive adherence to be higher than it actually is. Implementation strategies involving all intensive care unit staff are needed to overcome this gap between current evidence-based knowledge, practice, and perception.

Matrix metalloproteinases (MMPs) have been implicated in the pathophysiology of acute pulmonary embolism (APE)-induced pulmonary hypertension. Here, we evaluate the effects of atorvastatin pretreatment on APE-induced pulmonary hypertension, 24-hr mortality rate, and changes in plasma and lung MMP-2 and MMP-9 activities.Controlled animal study.University research laboratory.Male Wistar rats.Rats received atorvastatin (30 mg/kg/day orally) or tap water for 2 wks. In study 1, we examined whether atorvastatin affected APE-induced pulmonary hypertension by using a rat isolated lung perfusion model of APE. In study 2, we examined whether atorvastatin affects the survival rate after APE, which was induced by rapid intravenous injection of 14 mg/kg of a suspension of microspheres (or saline) into the tail vein.Plasma nitrite/nitrate concentrations were measured by chemiluminescence. Pretreatment with atorvastatin was associated with 49% higher nitrite/nitrate levels compared with controls (p.05). In study 1, whereas APE increased mean pulmonary artery pressure (MPAP) by 13.0 +/- 1.6 mm Hg in perfused lungs isolated from rats pretreated with water, pretreatment with atorvastatin attenuated by 27% the increases in MPAP after APE. In study 2, pretreatment with atorvastatin was associated with a significant increase in 24-hr survival rate after APE, which was 48% in embolized rats pretreated with water and 64% in rats pretreated with atorvastatin (p.05). Gelatin zymography of lung and plasma MMP-2 and MMP-9 was performed. Lungs and plasma from embolized rats showed higher levels of both pro- and activated forms of MMP-9 compared with those from nonembolized animals (all p.05). However, pretreatment with atorvastatin attenuated by 32% the increases in lung-activated MMP-9 levels after APE (p.05).These results suggest that pretreatment with atorvastatin attenuates APE-induced pulmonary hypertension and increases 24-hr survival rate by mechanisms that result in attenuated increases in lung activated MMP-9 after APE.

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.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.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.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 glucose150 mg/dL after initial stabilization; equivalence of continuous veno-veno hemofiltration and intermittent hemodialysis; lack of utility of bicarbonate use for pHor =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.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.

Objective: Endotracheal intubation is the gold standard for providing emergency ventilation, but acquiring and maintaining intubation skills may be difficult. Recent reports indicate that even in urban emergency medical services with a high call volume, esophageal intubations were observed, requiring either perfect intubation skills or development of alternatives for emergency ventilation. Design: Simulated emergency ventilation in apneic patients employing four different airway devices that used small tidal volumes. Setting: University hospital operating room. Subjects: Forty-eight ASA I/II patients who signed written informed consent before being enrolled into the study. Interventions: In healthy adult patients without underlying respiratory or cardiac disease who were breathing room air before undergoing routine induction of surgery, 12 experienced professional paramedics inserted either a laryngeal mask airway (n = 12), Combitube (n = 12), or cuffed oropharyngeal airway (n = 12) or placed a face mask (n = 12) before providing ventilation with a pediatric (maximum volume, 700 mL) self-inflating bag with 100% oxygen for 3 mins. Measurements and Main Results: In three of 12 cuffed oropharyngeal airway patients, two of 12 laryngeal mask airway patients, and one of 12 Combitube patients, oxygen saturation fell below 90% during airway device insertion, and the experiment was terminated; no oxygenation failures occurred with the bag-valve-mask. Oxygen saturation decreased significantly (p

Dexmedetomidine and propofol are commonly used sedatives in neurocritical care as they allow for frequent neurologic examinations. However, both agents are associated with significant hemodynamic side effects. The primary objective of this study is to compare the prevalence of severe hemodynamic effects in neurocritical care patients receiving dexmedetomidine and propofol.Multicenter, retrospective, propensity-matched cohort study.Neurocritical care units at two academic medical centers with dedicated neurocritical care teams and board-certified neurointensivists.Neurocritical care patients admitted between July 2009 and September 2012 were evaluated and then matched 1:1 based on propensity scoring of baseline characteristics.Continuous sedation with dexmedetomidine or propofol.A total of 342 patients (105 dexmedetomidine and 237 propofol) were included in the analysis, with 190 matched (95 in each group) by propensity score. The primary outcome of this study was a composite of severe hypotension (mean arterial pressure60 mm Hg) and bradycardia (heart rate50 beats/min) during sedative infusion. No difference in the primary composite outcome in both the unmatched (30% vs 30%, p = 0.94) or matched cohorts (28% vs 34%, p = 0.35) could be found. When analyzed separately, no differences could be found in the prevalence of severe hypotension or bradycardia in either the unmatched or matched cohorts.Severe hypotension and bradycardia occur at similar prevalence in neurocritical care patients who receive dexmedetomidine or propofol. Providers should similarly consider the likelihood of hypotension or bradycardia before starting either sedative.

Learning Objectives: The Society of Critical Care Medicine promotes a collaborative multidisciplinary practice, with a team consisting of professionals in different fields. Participation in social media activities, such as live-tweeting a meeting provides a unique opportunity for members of all professions to participate, and may allow for inclusion of a more diverse group in discussions. We assessed participation using social media metrics by physicians and non-physicians in conversations at the annual Critical Care Congress (CCC). Methods: Symplur Analytics were used to compare the characteristics of those who tweeted using the 2015 and 2016 CCC hashtag (#CCC44 and #CCC45, respectively). Characteristics of the top 50 participants during the conference were compared. Allied health professionals (AHP) were defined as non-physician healthcare providers. Results: There was an increase in tweets and participants from 2015 (4,374 tweets, 625 participants) to 2016 (14,358 tweets, 1,693 participants). In 2015, 27 of the top 50 tweeters were physicians, 7 were AHP (2 nurses, 2 advanced practitioners, and 1 pharmacist), 10 were organizations, and 6 were other non-healthcare individuals. In 2016, 22 of the top 50 tweeters were physicians, 17 were AHP (2 nurses, 5 advanced practitioners, 5 pharmacists, 2 dietitians, and 3 other providers), 8 were organizations, and 3 were other non-healthcare individuals. There were significantly more AHP participating in social media during 2016 CCC compared to 2015 (34% vs 14% of the top 50 accounts; p=0.047). The number of followers of AHP accounts were significantly fewer than the number of followers of the physician accounts (800 ± 626 followers vs 1,608 ± 2,282 followers; p=0.02), but there was no significant difference in number of tweets (7,403 ± 8,993 vs 16,764 ± 36,230 tweets; p=0.1) or duration of time on Twitter (4.8 ± 2.3 vs 5.1 ± 2.1 yrs; p=0.6). Conclusions: Social media is another way to engage all heath care professionals in academic conversations that occur during CCC. More effort should be made to increase inclusion in this important venue for multidisciplinary conversation.

Objective In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for fluid resuscitation in 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 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 Fluid resuscitation of severe sepsis may consist of natural or artificial colloids or crystalloids. Fluid challenge should be administered and repeated based on response (increase in blood pressure and urine output) and tolerance (evidence of intravascular volume overload).