Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354:449-61. [PMID: 16452557]

Conclusion: Intensive insulin therapy decreases morbidity but has no effect on the mortality of ICU patients.

Commentary: Intensive insulin therapy was most effective in patients treated in the medical ICU for 3 or more days, but these patients are not easily identifiable at the time of ICU admission, and the treatment may be harmful in patients with an ICU stay fewer than 3 days, perhaps related to episodes of hypoglycemia. This study did not derail tight glycemic control as a standard in ICU care, but it highlighted the importance of careful monitoring for hypoglycemia within the first 3 days, particularly in the unconscious or comatose patient. There is still considerable controversy on the target glucose level at the time of admission to the ICU, but the recommendation of 8.33 mmol/L (150 mg/dL) for the first 3 days seems a reasonable goal after nutrition and resuscitation are established (1). In addition, given that a previous study demonstrated a large benefit for insulin in the ICU setting (2), this study demonstrates the phenomenon of exaggeration of positive results when trials are stopped early because of benefit (3, 4) and highlights the importance of follow-up studies in populations for whom treatment recommendations are being developed.

Clinical Bottom Line: Patients admitted to a medical ICU should have careful glucose monitoring. A reasonable target glucose value might be less than 8.3 mmol/L (<150 mg/dL) in the first 3 days, and 4.4 to 5.6 mmol/L (80 to 100 mg/dL) thereafter.

Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34:1589-96. [PMID: 16625125]

Conclusion: Effective antimicrobial administration within the first hour of documented hypotension is associated with increased survival in adult patients with septic shock.

Commentary: This study documents substantial delays that still exist in the administration of effective antimicrobial therapy for septic shock. The findings upgrade the evidence for starting intravenous antibiotic therapy within the first hour of recognition of severe sepsis, after appropriate cultures have been obtained, and they support the Surviving Sepsis Campaign practice guidelines (see http://www.survivingsepsis.org/files/surviving_sepsis_campaign_guidelines.pdf) . Health care systems and teams should develop ways to ensure that antibiotics are given during initial attempts at resuscitation.

Clinical Bottom Line: In patients with septic shock, administer antimicrobial therapy for isolated or suspected pathogens within the first hour of documented hypotension.

National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wiedeman HP, Wheeler AP, Bernard GR; et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354:2564-75. [PMID: 16714767]

Conclusion: A conservative strategy of fluid management does not reduce 60-day mortality in patients with acute lung injury, but it improves lung function and shortens the duration of mechanical ventilation and intensive care without increasing the risk for nonpulmonary organ failure.

Commentary: This study demonstrates that a conservative fluid strategy that roughly matches 24-hour input to output helps patients wean from mechanical ventilation after appropriate initial fluid resuscitation (6). The trial was 1 of 2 that also tested catheter type (see following summary), and the researchers also found no benefit of a specific catheter type on fluid management strategy. The generalizability of the findings is limited, however, because only 1001 of 11 512 screened patients participated in the trial.

Clinical Bottom Line: Fluids in patients with acute lung injury who resemble those in this study should be managed conservatively according to the protocol used in this study.

National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wheeler AP, Bernard GR, Thompson BT, et al. Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med. 2006;354:2213-24. [PMID: 16714768]

Conclusion: Pulmonary artery catheter–guided therapy did not improve survival or organ function and was associated with more complications than CVC-guided therapy.

Commentary: This excellent study demonstrated that PAC-guided therapy should not be routinely used in the management of acute lung injury. Although the authors attributed the increased incidence of arrhythmias among patients who received a PAC to the arrhythmogenic effects of the PAC and its insertion, the increased use of vasopressors (36% in the PAC group vs. 30% in the CVC group) might have accounted for these arrhythmias (7, 8).

Clinical Bottom Line: Pulmonary artery catheters should not routinely be used for the management of acute lung injury.

Canadian Critical Care Trials Group. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med. 2006;355:2619-30. [PMID: 17182987]

Conclusion: Bronchoalveolar lavage with quantitative culture of the bronchoalveolar lavage fluid and endotracheal aspiration with nonquantitative culture of the aspirate were associated with similar clinical outcomes and similar overall use of antibiotics in patients with ventilator-associated pneumonia.

Commentary: Although bronchoalveolar lavage did not influence in-hospital death or length of stay, it might theoretically still play a role by helping providers taper or discontinue unnecessary antimicrobial therapy. Few if any definitive studies document the outcomes of this approach, however (9). In addition, as pointed out in an accompanying editorial (10), about 40% of patients screened for the trial were excluded, and these excluded patients in practice often undergo real-time evaluation for suspected ventilator-associated pneumonia. Thus, the generalizability of the study findings is limited.

Clinical Bottom Line: In patients who resemble those in this trial, endotracheal aspiration with nonquantitative culture may be preferable to bronchoalveolar lavage with quantitative culture as a way to diagnose ventilator-associated pneumonia because it is less invasive.

Fowler VG, Boucher GW, Corey GR, et al; S. aureus Endocarditis and Bacteremia Study Group. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006;355:653-65. [PMID: 16914701]

Conclusion: Daptomycin was noninferior to standard therapy for the treatment of S. aureus bacteremia and endocarditis.

Commentary: The decline in development of new antibiotics, recognition of vancomycin treatment failures, and emergence of new community-associated methicillin-resistant S. aureus strains have led to a rethinking of treatment options for S. aureus bacteremia and endocarditis. Therefore, daptomycin is a welcome addition. However, the drug is expensive, and it has poor penetration into lung tissue (11).

Clinical Bottom Line: Daptomycin is a reasonable alternative to standard therapies for hospitalized patients with S. aureus bacteremia and endocarditis.

Nelson JE, Angus DC, Weissfeld LA, et al; Critical Care Peer Workgroup of the Promoting Excellence in End-of-Life Care Project. End-of-life care for the critically ill: a national intensive care unit survey. Crit Care Med. 2006;34:2547-53. [PMID: 16932230]

Conclusion: Important barriers to optimal end-of-life care exist, and strategies to address them are not widely available.

Commentary: Deeply ingrained attitudes and behaviors of both clinicians and the public are important barriers to better end-of-life care, and they have been difficult to modify. Broader education of the public about critical illness, limitations of critical care therapies, appropriate treatment goals, and the importance and benefits of palliative interventions may bring expectations into closer alignment with ICU realities. In addition, providers can implement regular meetings with families in the ICU at least every 72 hours to decrease patient length of stay without worsening survival (12); develop a bereavement brochure to reduce the emotional burden on families (13); and consider training in communication and symptom management, such as that offered by the American Academy of Hospice and Palliative Medicine programs (http://www.aahpm.org), or university-based programs, such as the Program in Palliative Care Education and Practice (http://www.hms.harvard.edu/cdi/pallcare). Palliative care consultation should also be used, if available.

1. Malhotra A. Intensive insulin in intensive care [Editorial]. N Engl J Med. 2006;354:516-8. [PMID: 16452564].[Free Full Text]

2. van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345:1359-67. [PMID: 11794168].[Abstract/Free Full Text]

3. Aberegg SK. Intensive insulin therapy in the medical ICU [Letter]. N Engl J Med. 2006;354:2069-71; author reply 2069-71. [PMID: 16696141].[Free Full Text]

4. Mueller PS, Montori VM, Bassler D, Koenig BA, Guyatt GH. Ethical issues in stopping randomized trials early because of apparent benefit. Ann Intern Med. 2007;146:878-81. [PMID: 17577007].[Abstract/Free Full Text]

5. Surviving Sepsis Campaign Management Guidelines Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858-73. [PMID: 15090974].[Medline]

6. Qushmaq I. A conservative fluid management strategy did not affect risk for death but shortened duration of ventilation in acute lung injury. ACP J Club. 2006;145:69 [PMID: 17080981].[Medline]

7. Shure D. Pulmonary-artery catheters—peace at last? [Editorial]. N Engl J Med. 2006;354:2273-4. [PMID: 16714770].[Free Full Text]

8. Pastewski AA, Kupfer Y, Tessler S. Catheters and the treatment of acute lung injury [Letter]. N Engl J Med. 2006;355:956 [PMID: 16943411].[Free Full Text]

9. Shorr AF, Sherner JH, Jackson WL, Kollef MH. Invasive approaches to the diagnosis of ventilator-associated pneumonia: a meta-analysis. Crit Care Med. 2005;33:46-53. [PMID: 15644647].[Medline]

10. Kollef MH. Diagnosis of ventilator-associated pneumonia [Editorial]. N Engl J Med. 2006;355:2691-3. [PMID: 17182995].[Free Full Text]

11. Grayson ML. The treatment triangle for staphylococcal infections [Editorial]. N Engl J Med. 2006;355:724-7. [PMID: 16914709].[Free Full Text]

12. Lilly CM, Sonna LA, Haley KJ, Massaro AF. Intensive communication: four-year follow-up from a clinical practice study. Crit Care Med. 2003;31:S394-9. [PMID: 12771590].[Medline]

13. Lautrette A, Darmon M, Megarbane B, Joly LM, Chevret S, Adrie C, et al. A communication strategy and brochure for relatives of patients dying in the ICU. N Engl J Med. 2007;356:469-78. [PMID: 17267907].[Abstract/Free Full Text]