2003 Glucose Control and Mortality in Critically Ill Patients

Simon J. Finney, MBChB, MRCPCornelia Zekveld, BScAndi Elia, BScTimothy W. Evans, MD, DSc, FRCP 

JAMA. 2003;290:2041-2047.

 

ABSTRACT


Context  Hyperglycemia is common in critically ill patients,
 even in those without diabetes mellitus. Aggressive glycemic control may reduce mortality in this population. However, the relationship between mortality, the control of hyperglycemia, and the administration of exogenous insulin is unclear.


Objective  To determine whether blood glucose level or quantity of insulin administered is associated with reduced mortality in critically ill patients.

Design, Setting, and Patients  Single-center, prospective, observational study of 531 patients (median age, 64 years) newly admitted over the first 6 months of 2002 to an adult intensive care unit (ICU) in a UK national referral center for cardiorespiratory surgery and medicine.

Main Outcome Measures  The primary end point was intensive care unit (ICU) mortality. Secondary end points were hospital mortality, ICU and hospital length of stay, and predicted threshold glucose level associated with risk of death.

Results  Of 531 patients admitted to the ICU, 523 underwent analysis of their glycemic control. Twenty-four-hour control of blood glucose levels was variable. Rates of ICU and hospital mortality were 5.2% and 5.7%, respectively; median lengths of stay were 1.8 (interquartile range, 0.9-3.7) days and 6 (interquartilerange, 4.5-8.3) days, respectively. Multivariable logistic regression demonstrated that increased administration of insulin was positively and significantly associated with ICU mortality (odds ratio, 1.02 [95% confidence interval, 1.01-1.04] at a prevailing glucose level of 111-144 mg/dL [6.1-8.0 mmol/L] for a 1-IU/d increase),suggesting that mortality benefits are attributable to glycemic control rather than increased administration of insulin. Also, the regression models suggest that a mortality benefit accrues below a predicted threshold glucose level of 144 to 200 mg/dL (8.0-11.1 mmol/L), with a speculative upper limit of 145 mg/dL (8.0 mmol/L) for the target blood glucose level.

Conclusions  Increased insulin administration is positively associated with death in the ICU regardless of the prevailing blood glucose level. Thus, control of glucose levels rather than of absolute levels of exogenous insulin appear to account for the mortality benefit associated with intensive insulin therapy demonstrated by others.


2003 Acute Respiratory Distress Syndrome in Critically Ill Patients With Severe Acute Respiratory Syndrome

Thomas W. K. Lew, MMed, EDIC; Tong-Kiat Kwek, MMed; Dessmon Tai, FRCPE, FCCM; Arul Earnest, MSc; Shi Loo, MMed, EDIC; Kulgit Singh, MMed;Kim Meng Kwan, MMed; Yeow Chan, MMed; Chik Foo Yim, MMed; Siam Lee Bek, MBBS; Ai Ching Kor, MRCP; Wee See Yap, MRCP; Y. Rubuen Chelliah, MMed;Yeow Choy Lai, MMed; Soon-Keng Goh, FRCPE, EDIC

JAMA. 2003;290:374-380.


ABSTRACT


Context Severe acute respiratory syndrome (SARS) is an emerging infectious disease with a 25% incidence of progression to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and mortality exceeding 10%.

Objective To describe the clinical spectrum and outcomes of ALI/ARDS in patients with SARS-related critical illness.

Design, Setting, and Patients Retrospective case series of adult patients with probable SARS admitted to the intensive care unit (ICU) of a hospital in Singapore between March 6 and June 6, 2003.

Main Outcome Measures The primary outcome measure was 28-day mortality after symptom onset.

Results Of 199 patients hospitalized with SARS, 46 (23%) were admitted to the ICU, including 45 who fulfilled criteria for ALI/ARDS. Mortality at 28 days for the entire cohort was 20 (10.1%) of 199 and for ICU patients was 17 (37%) of 46. Intensive care unit mortality at 13 weeks was 24 (52.2%) of 46. Nineteen of 24 ICU deaths occurred late (7 days after ICU admission) and were attributed to complications related to severe ARDS, multiorgan failure, thromboembolic complications, or septicemic shock. ARDS was characterized by ease of derecruitment of alveoli and paucity of airway secretion, bronchospasm, or dynamic hyperinflation. Lower Acute Physiology and Chronic Health Evaluation II scores and higher baseline ratios of PaO2 to fraction of inspired oxygen were associated with earlier recovery.

Conclusions Critically ill patients with SARS and ALI/ARDS had characteristic clinical findings, high rates of complications; and high mortality. These findings may provide useful information for optimizing supportive care for SARS-related critical illness.

2007 Benefits and Risks of Tight Glucose Control in Critically Ill Adults - A Meta-analysis

A Meta-analysis

Renda Soylemez Wiener, MD, MPHDaniel C. Wiener, MDRobin J. Larson, MD, MPH 

JAMA. 2008;300(8):933-944.

ABSTRACT


Context  The American Diabetes Association and Surviving
 Sepsis Campaign recommend tight glucose control in critically ill patients based largely on 1 trial that shows decreased mortality in a surgical intensive care unit. Because similar studies report conflicting results and tight glucose control can cause dangeroushypoglycemia, the data underlying this recommendation should be critically evaluated.

 

Objective  To evaluate benefits and risks of tight glucose control vs usual care in critically ill adult patients.

Data Sources  MEDLINE (1950-2008), the Cochrane Library, clinical trial registries, reference lists, and abstracts from conferences from both the American Thoracic Society (2001-2008) and the Society of Critical Care Medicine (2004-2008).

Study Selection  We searched for studies in any language in which adult intensive care patients were randomly assigned to tight vs usual glucose control. Of 1358 identified studies, 34 randomized trials (23 full publications, 9 abstracts, 2 unpublished studies) met inclusion criteria.

Data Extraction and Analysis  Two reviewers independently extracted information using a prespecified protocol and evaluated methodological quality with a standardized scale. Study investigators were contacted for missing details. We used both random- and fixed-effects models to estimate relative risks (RRs).

Results  Twenty-nine randomized controlled trials totaling 8432 patients contributed data for this meta-analysis. Hospital mortality did not differ between tight glucose control and usual care overall (21.6% vs 23.3%; RR, 0.93; 95% confidence interval [CI], 0.85-1.03). There was also no significant difference in mortality when stratified by glucose goal ([1] very tight: ≤110 mg/dL; 23% vs 25.2%; RR, 0.90; 95% CI, 0.77-1.04; or [2] moderately tight: <150 mg/dL; 17.3% vs 18.0%; RR, 0.99; 95% CI, 0.83-1.18) or intensive care unit setting ([1] surgical: 8.8% vs 10.8%; RR, 0.88; 95% CI, 0.63-1.22; [2] medical: 26.9% vs 29.7%; RR, 0.92; 95% CI, 0.82-1.04; or [3] medical-surgical: 26.1% vs 27.0%; RR, 0.95; 95% CI, 0.80-1.13). Tight glucose control was not associated with significantly decreased risk for new need fordialysis (11.2% vs 12.1%; RR, 0.96; 95% CI, 0.76-1.20), but was associated with significantly decreased risk of septicemia (10.9% vs 13.4%; RR, 0.76; 95% CI, 0.59-0.97), and significantly increased risk of hypoglycemia (glucose ≤40 mg/dL; 13.7% vs 2.5%; RR, 5.13; 95% CI, 4.09-6.43).

Conclusion  In critically ill adult patients, tight glucose control is not associated with significantly reduced hospital mortality but is associated with an increased risk of hypoglycemia.

2003 Critically Ill Patients With Severe Acute Respiratory Syndrome

Robert A. Fowler, MD, MS; Stephen E. Lapinsky, MB, BCh, MSc; David Hallett, MSc; Allan S. Detsky, MD, PhD; William J. Sibbald, MD; Arthur S. Slutsky, MD;Thomas E. Stewart, MD; for the Toronto SARS Critical Care Group


JAMA. 2003;290:367-373.

Context Severe acute respiratory syndrome (SARS) is a newly recognized infectious disease capable of causing severe respiratory failure.

Objective To determine the epidemiological features, course, and outcomes of patients with SARS-related critical illness.

Design, Setting, and Patients Retrospective case series of 38 adult patients with SARS-related critical illness admitted to 13 intensive care units (ICUs) in the Toronto area between the onset of the outbreak and April 15, 2003. Data were collected daily during the first 7 days in the ICUs, and patients were followed up for 28 days.

Main Outcome Measures The primary outcome was mortality at 28 days after ICU admission. Secondary outcomes included rate of SARS-related critical illness, number of tertiary care ICUs and staff placed under quarantine, and number of health care workers (HCWs) contracting SARS secondary to ICU-acquiredtransmission.

Results Of 196 patients with SARS, 38 (19%) became critically ill, 7 (18%) of whom were HCWs. The median (interquartile range [IQR]) age of the 38 patients was 57.4 (39.0-69.6) years. The median (IQR) duration between initial symptoms and admission to the ICU was 8 (5-10) days. Twenty-nine (76%) required mechanical ventilation and 10 of these (34%) experienced barotrauma. Mortality at 28 days was 13 (34%) of 38 patients and for those requiring mechanical ventilation, mortality was 13 (45%) of 29. Six patients (16%) remained mechanically ventilated at 28 days. Two of these patients had died by 8 weeks' follow-up. Patients who died were more often older, had preexisting diabetes mellitus, and on admission to hospital were more likely to have bilateral radiographic infiltrates. Transmission of SARS in 6 study ICUs led to closure of 73 medical-surgical ICU beds. In 2 university ICUs, 164 HCWs were quarantined and 16 (10%) developed SARS.

Conclusions Critical illness was common among patients with SARS. Affected patients had primarily single-organ respiratory failure, and half of mechanically ventilated patients died.The SARS outbreak greatly strained regional critical care resources.

2008 Effect of Evidence-Based Feeding Guidelines on Mortality of Critically Ill Adults - A Cluster Randomized Controlled Trial

Gordon S. Doig, PhD; Fiona Simpson, MND; Simon Finfer, FJFICM; Anthony Delaney, FJFICM; Andrew R. Davies, FJFICM; Imogen Mitchell, FJFICM; Geoff Dobb, FJFICM; for the Nutrition Guidelines Investigators of the ANZICS Clinical Trials Group

JAMA. 2008;300(23):2731-2741.

Context  Evidence demonstrates that providing nutritional support to intensive care unit (ICU) patients within 24 hours of ICU admission reduces mortality. However, early feeding is not universally practiced. Changing practice in complex multidisciplinary environments is difficult. Evidence supporting whether guidelines can improve ICU feeding practices and patient outcomes is contradictory.

Objective  To determine whether evidence-based feeding guidelines, implemented using a multifaceted practice change strategy, improve feeding practices and reduce mortality in ICU patients.

Design, Setting, and Patients  Cluster randomized trial in ICUs of 27 community and tertiary hospitals in Australia and New Zealand. Between November 2003 and May 2004, 1118 critically ill adult patients expected to remain in the ICU longer than 2 days were enrolled. All participants completed the study.

Interventions  Intensive care units were randomly assigned to guideline or control groups. Guideline ICUs developed an evidence-based guideline using Browman's Clinical Practice Guideline Development Cycle. A practice-change strategy composed of 18 specific interventions, leveraged by educational outreach visits, was implemented in guideline ICUs.

Main Outcome Measures  Hospital discharge mortality. Secondary outcomes included ICU and hospital length of stay, organ dysfunction, and feeding process measures.

Results  Guideline and control ICUs enrolled 561 and 557 patients, respectively. Guideline ICUs fed patients earlier (0.75 vs 1.37 mean days to enteral nutrition start; difference, –0.62 [95% confidence interval {CI}, –0.82 to –0.36]; P < .001 and 1.04 vs 1.40 mean days to parenteral nutrition start; difference, –0.35 [95% CI, –0.61 to –0.01]; P = .04) and achieved caloric goals more often (6.10 vs 5.02 mean days per 10 fed patient-days; difference, 1.07 [95% CI, 0.12 to 2.22]; P = .03). Guideline and control ICUs did not differ with regard to hospital discharge mortality (28.9% vs 27.4%; difference, 1.4% [95% CI, –6.3% to 12.0%]; P = .75) or to hospital length of stay (24.2 vs 24.3 days; difference, –0.08 [95% CI, –3.8 to 4.4]; P = .97) or ICU length of stay (9.1 vs 9.9 days; difference, –0.86 [95% CI, –2.6 to 1.3]; P = .42).

Conclusions  Using a multifaceted practice change strategy, ICUs successfully developed and introduced an evidence-based nutritional support guideline that promoted earlier feeding and greater nutritional adequacy. However, use of the guideline did not improve clinical outcomes.

Trial Registration  anzctr.org.au Identifier: ACTRN12608000407392

Author Affiliations: Northern Clinical School, Royal North Shore Hospital, University of Sydney, Sydney, Australia (Drs Doig and Delaney and Ms Simpson); Royal North Shore Hospital and Faculty of Medicine, University of Sydney (Dr Finfer); The Alfred Hospital, Melbourne, Australia (Dr Davies); Canberra Hospital, Canberra, Australia (Dr Mitchell); and Royal Perth Hospital, Perth, Australia (Dr Dobb).

 

Also refer to the editorial:

Implementing Nutrition Guidelines in the Critical Care Setting

A Worthwhile and Achievable Goal?

Naomi E. Jones, RD, MSc; Daren K. Heyland, MD, FRCPC

JAMA. 2008;300(23):2798-2799.

2007 Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial

JAMA. 2007 Dec 12;298(22):2644-53.

Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, Shintani AK, Thompson JL, Jackson JC, Deppen SA, Stiles RA, Dittus RS, Bernard GR, Ely EW. 

Department of Anesthesiology/Division of Critical Care, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.

CONTEXT: Lorazepam is currently recommended for sustained sedation of mechanically ventilated intensive care unit (ICU) patients, but this and other benzodiazepine drugs may contribute to acute brain dysfunction, ie, delirium and coma, associated with prolonged hospital stays, costs, and increased mortality. Dexmedetomidine induces sedation via different central nervous system receptors than the benzodiazepine drugs and may lower the risk of acute brain dysfunction. OBJECTIVE: To determine whether dexmedetomidine reduces the duration of delirium and coma in mechanically ventilated ICU patients while providing adequate sedation as compared with lorazepam. DESIGN, SETTING, PATIENTS, AND INTERVENTION: Double-blind, randomized controlled trial of 106 adult mechanically ventilated medical and surgical ICU patients at 2 tertiary care centers between August 2004 and April 2006. Patients were sedated with dexmedetomidine or lorazepam for as many as 120 hours. Study drugs were titrated to achieve the desired level of sedation, measured using the Richmond Agitation-Sedation Scale (RASS). Patients were monitored twice daily for delirium using the Confusion Assessment Method for the ICU (CAM-ICU). MAIN OUTCOME MEASURES: Days alive without delirium or coma and percentage of days spent within 1 RASS point of the sedation goal. RESULTS: Sedation with dexmedetomidine resulted in more days alive without delirium or coma (median days, 7.0 vs 3.0; P = .01) and a lower prevalence of coma (63% vs 92%; P < .001) than sedation with lorazepam. Patients sedated with dexmedetomidine spent more time within 1 RASS point of their sedation goal compared with patients sedated with lorazepam (median percentage of days, 80% vs 67%; P = .04). The 28-day mortality in the dexmedetomidine group was 17% vs 27% in the lorazepam group (P = .18) and cost of care was similar between groups. More patients in the dexmedetomidine group (42% vs 31%; P = .61) were able to complete post-ICU neuropsychological testing, with similar scores in the tests evaluating global cognitive, motor speed, and attention functions. The 12-month time to death was 363 days in the dexmedetomidine group vs 188 days in the lorazepam group (P = .48). CONCLUSION: In mechanically ventilated ICU patients managed with individualized targeted sedation, use of a dexmedetomidine infusion resulted in more days alive without delirium or coma and more time at the targeted level of sedation than with a lorazepam infusion. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00095251.

2008 Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome (LOV): a randomized controlled trial

JAMA. 2008 Feb 13;299(6):637-45.

Meade MO, Cook DJ, Guyatt GH, Slutsky AS, Arabi YM, Cooper DJ, Davies AR, Hand LE, Zhou Q, Thabane L, Austin P, Lapinsky S, Baxter A, Russell J, Skrobik Y, Ronco JJ, Stewart TE; Lung Open Ventilation Study Investigators.

Department of Medicine, McMaster University, Hamilton, Ontario, Canada. This email address is being protected from spambots. You need JavaScript enabled to view it.

CONTEXT: Low-tidal-volume ventilation reduces mortality in critically ill patients with acute lung injury and acute respiratory distress syndrome. Instituting additional strategies to open collapsed lung tissue may further reduce mortality. OBJECTIVE: To compare an established low-tidal-volume ventilation strategy with an experimental strategy based on the original "open-lung approach," combining low tidal volume, lung recruitment maneuvers, and high positive-end-expiratory pressure. DESIGN AND SETTING: Randomized controlled trial with concealed allocation and blinded data analysis conducted between August 2000 and March 2006 in 30 intensive care units in Canada, Australia, and Saudi Arabia. PATIENTS: Nine hundred eighty-three consecutive patients with acute lung injury and a ratio of arterial oxygen tension to inspired oxygen fraction not exceeding 250. INTERVENTIONS: The control strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau airway pressures not exceeding 30 cm H2O, and conventional levels of positive end-expiratory pressure (n = 508). The experimental strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau pressures not exceeding 40 cm H2O, recruitment maneuvers, and higher positive end-expiratory pressures (n = 475). MAIN OUTCOME MEASURE: All-cause hospital mortality. RESULTS: Eighty-five percent of the 983 study patients met criteria for acute respiratory distress syndrome at enrollment. Tidal volumes remained similar in the 2 groups, and mean positive end-expiratory pressures were 14.6 (SD, 3.4) cm H2O in the experimental group vs 9.8 (SD, 2.7) cm H2O among controls during the first 72 hours (P < .001). All-cause hospital mortality rates were 36.4% and 40.4%, respectively (relative risk [RR], 0.90; 95% confidence interval [CI], 0.77-1.05; P = .19). Barotrauma rates were 11.2% and 9.1% (RR, 1.21; 95% CI, 0.83-1.75; P = .33). The experimental group had lower rates of refractory hypoxemia (4.6% vs 10.2%; RR, 0.54; 95% CI, 0.34-0.86; P = .01), death with refractory hypoxemia (4.2% vs 8.9%; RR, 0.56; 95% CI, 0.34-0.93; P = .03), and previously defined eligible use of rescue therapies (5.1% vs 9.3%; RR, 0.61; 95% CI, 0.38-0.99; P = .045). CONCLUSIONS: For patients with acute lung injury and acute respiratory distress syndrome, a multifaceted protocolized ventilation strategy designed to recruit and open the lung resulted in no significant difference in all-cause hospital mortality or barotrauma compared with an established low-tidal-volume protocolized ventilation strategy. This "open-lung" strategy did appear to improve secondary end points related to hypoxemia and use of rescue therapies. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00182195.

2008 Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial (EXPRESS)

JAMA. 2008 Feb 13;299(6):646-55.

Mercat A, Richard JC, Vielle B, Jaber S, Osman D, Diehl JL, Lefrant JY, Prat G, Richecoeur J, Nieszkowska A, Gervais C, Baudot J, Bouadma L, Brochard L; Expiratory Pressure (Express) Study Group.

Département de Réanimation Médicale et Médecine Hyperbare, CHU d'Angers, Angers, France. This email address is being protected from spambots. You need JavaScript enabled to view it.

CONTEXT: The need for lung protection is universally accepted, but the optimal level of positive end-expiratory pressure (PEEP) in patients with acute lung injury (ALI) or acute respiratory distress syndrome remains debated. OBJECTIVE:
To compare the effect on outcome of a strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation to one aimed at minimizing alveolar distension in patients with ALI. DESIGN, SETTING, AND PATIENTS: A multicenter randomized controlled trial of 767 adults (mean [SD] age, 59.9 [15.4] years) with ALI conducted in 37 intensive care units in France from September 2002 to December 2005. INTERVENTION: Tidal volume was set at 6 mL/kg of predicted body weight in both strategies. Patients were randomly assigned to a moderate PEEP strategy (5-9 cm H(2)O) (minimal distension strategy; n = 382) or to a level of PEEP set to reach a plateau pressure of 28 to 30 cm H(2)O (increased recruitment strategy; n = 385). MAIN OUTCOME MEASURES: The primary end point was mortality at 28 days. Secondary end points were hospital mortality at 60 days, ventilator-free days, and organ failure-free days at 28 days. RESULTS: The 28-day mortality rate in the minimal distension group was 31.2% (n = 119) vs 27.8% (n = 107) in the increased recruitment group (relative risk, 1.12 [95% confidence interval, 0.90-1.40]; P = .31). The hospital mortality rate in the minimal distension group was 39.0% (n = 149) vs 35.4% (n = 136) in the increased recruitment group (relative risk, 1.10 [95% confidence interval, 0.92-1.32]; P = .30). The increased recruitment group compared with the minimal distension group had a higher median number of ventilator-free days (7 [interquartile range {IQR}, 0-19] vs 3 [IQR, 0-17]; P = .04) and organ failure-free days (6 [IQR, 0-18] vs 2 [IQR, 0-16]; P = .04). This strategy also was associated with higher compliance values, better oxygenation, less use of adjunctive therapies, and larger fluid requirements. CONCLUSIONS: A strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality. However, it did improve lung function and reduced the duration of mechanical ventilation and the duration of organ failure. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00188058.

2008 Cytomegalovirus reactivation in critically ill immunocompetent patients

JAMA. 2008 Jul 23;300(4):413-22.

Limaye AP, Kirby KA, Rubenfeld GD, Leisenring WM, Bulger EM, Neff MJ, Gibran NS,
Huang ML, Santo Hayes TK, Corey L, Boeckh M.

Department of Laboratory Medicine, University of Washington Medical Center, 1959
NE Pacific St, Seattle, WA 98195-7110, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.

CONTEXT: Cytomegalovirus (CMV) infection is associated with adverse clinical
outcomes in immunosuppressed persons, but the incidence and association of CMV
reactivation with adverse outcomes in critically ill persons lacking evidence of
immunosuppression have not been well defined. OBJECTIVE: To determine the
association of CMV reactivation with intensive care unit (ICU) and hospital
length of stay in critically ill immunocompetent persons. DESIGN, SETTING, AND
PARTICIPANTS: We prospectively assessed CMV plasma DNAemia by thrice-weekly
real-time polymerase chain reaction (PCR) and clinical outcomes in a cohort of
120 CMV-seropositive, immunocompetent adults admitted to 1 of 6 ICUs at 2
separate hospitals at a large US tertiary care academic medical center between
2004 and 2006. Clinical measurements were assessed by personnel blinded to CMV
PCR results. Risk factors for CMV reactivation and association with hospital and
ICU length of stay were assessed by multivariable logistic regression and
proportional odds models. MAIN OUTCOME MEASURES: Association of CMV reactivation
with prolonged hospital length of stay or death. RESULTS: The primary composite
end point of continued hospitalization (n = 35) or death (n = 10) by 30 days
occurred in 45 (35%) of the 120 patients. Cytomegalovirus viremia at any level
occurred in 33% (39/120; 95% confidence interval [CI], 24%-41%) at a median of 12
days (range, 3-57 days) and CMV viremia greater than 1000 copies/mL occurred in
20% (24/120; 95% CI, 13%-28%) at a median of 26 days (range, 9-56 days). By
logistic regression, CMV infection at any level (adjusted odds ratio [OR], 4.3;
95% CI, 1.6-11.9; P = .005) and at greater than 1000 copies/mL (adjusted OR,
13.9; 95% CI, 3.2-60; P < .001) and the average CMV area under the curve (AUC) in
log(10) copies per milliliter (adjusted OR, 2.1; 95% CI, 1.3-3.2; P < .001) were
independently associated with hospitalization or death by 30 days. In
multivariable partial proportional odds models, both CMV 7-day moving average
(OR, 5.1; 95% CI, 2.9-9.1; P < .001) and CMV AUC (OR, 3.2; 95% CI, 2.1-4.7; P <
.001) were independently associated with a hospital length of stay of at least 14
days. CONCLUSIONS: These preliminary findings suggest that reactivation of CMV
occurs frequently in critically ill immunocompetent patients and is associated
with prolonged hospitalization or death. A controlled trial of CMV prophylaxis in
this setting is warranted.

2008 Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: the NASCENT randomized trial

JAMA. 2008 Aug 20;300(7):805-13.

Kollef MH, Afessa B, Anzueto A, Veremakis C, Kerr KM, Margolis BD, Craven DE,
Roberts PR, Arroliga AC, Hubmayr RD, Restrepo MI, Auger WR, Schinner R; NASCENT
Investigation Group.

Collaborators: Afessa B, Hubmayr R, Wilson G, Ansari T, Manchester T, Anzueto A,
Restrepo MI, Bakhta S, Fiedler D, Kucera S, Houlihan T, Arroliga AC, Isabella T,
Komara J, Ferrari M, Carney D, Blosser S, Novchich T, Collin G, Bernstein B,
Coppa G, Temperino M, Craven DE, DiGregorio S, Lamb C, Polcaro J, Criner G,
Grabianowski C, Dellinger P, Stillwell C, DeMarini T, Maslanka N, Allen B,
Douglas I, Lathrop D, Freilich E, Amin D, Woods LM, Phillips T, Freire A,
Thompson S, Umberger R, Friedman B, Redman D, Wilson J, Gallagher JT, Wishin J,
Lavon AJ, Caruso L, Gabrielli A, Bennett N, Ginzburg E, Derr B, Hata SJ, Shelsky
C, Herr D, Bolouri N, Hyzy R, Cooperson D, Johnson JE, Waldrum MR, Wille K,
O'Hare L, Kaplan C, Dettenmeire P, Katragadda S, Steinhauser T, Kaufman D, Harvey
T, Keene A, Moltz K, Koppisetti S, Liz M, Kerr K, Auger W, Munden B, Gabel L,
Kindt G, Funke LM, Athmann L, Kirtland S, Zeller J, Klapholz A, Hardinge L,
Klausner H, Defoe LA, Kollef M, Doyle A, Lange N, Giambartolomei S, Thoutt G,
Lawlor DP, Schroeder ML, Leeper K, Weyers C, Manasia A, Delguidice R, Mapel D,
Ponder R, Margolis B, Doornbos C, Martin C, Morrow L, Galkowski M, Niederman M,
Jacobs P, Pastores S, Alicea M, Schneider L, Phillips C, Bacon K, Roberts P,
Bennett J, Rodricks M, Mattix C, Rodriguez W, Yapor PJ, Ayala G, Scheinberg P,
Bensen C, Sanders R, Schelbar EJ, Boomer WM, Goulet JK, Sluss J, Simpson S,
Conyers K, Summer W, Romaine C, Sy A, McFarland E, Thompson AB, Scheetz M,
Veremakis C, O'Brien J, Willms D, Middlebrook S, Wood KA, Abraham A, Carlins JH,
Griffin-Glatz V.

Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110,
USA. This email address is being protected from spambots. You need JavaScript enabled to view it.

CONTEXT: Ventilator-associated pneumonia (VAP) causes substantial morbidity. A
silver-coated endotracheal tube has been designed to reduce VAP incidence by
preventing bacterial colonization and biofilm formation. OBJECTIVE: To determine
whether a silver-coated endotracheal tube would reduce the incidence of
microbiologically confirmed VAP. DESIGN, SETTING, AND PARTICIPANTS: Prospective,
randomized, single-blind, controlled study conducted in 54 centers in North
America. A total of 9417 adult patients (> or = 18 years) were screened between
2002 and 2006. A total of 2003 patients expected to require mechanical
ventilation for 24 hours or longer were randomized. INTERVENTION: Patients were
assigned to undergo intubation with 1 of 2 high-volume, low-pressure endotracheal
tubes, similar except for a silver coating on the experimental tube. MAIN OUTCOME
MEASURES: Primary outcome was VAP incidence based on quantitative bronchoalveolar
lavage fluid culture with 10(4) colony-forming units/mL or greater in patients
intubated for 24 hours or longer. Other outcomes were VAP incidence in all
intubated patients, time to VAP onset, length of intubation and duration of
intensive care unit and hospital stay, mortality, and adverse events. RESULTS:
Among patients intubated for 24 hours or longer, rates of microbiologically
confirmed VAP were 4.8% (37/766 patients; 95% confidence interval [CI],
3.4%-6.6%) in the group receiving the silver-coated tube and 7.5% (56/743; 95%
CI, 5.7%-9.7%) (P = .03) in the group receiving the uncoated tube (all intubated
patients, 3.8% [37/968; 95% CI, 2.7%-5.2%] and 5.8% [56/964; 95% CI, 4.4%-7.5%]
[P = .04]), with a relative risk reduction of 35.9% (95% CI, 3.6%-69.0%; all
intubated patients, 34.2% [95% CI, 1.2%-67.9%]). The silver-coated endotracheal
tube was associated with delayed occurrence of VAP (P = .005). No statistically
significant between-group differences were observed in durations of intubation,
intensive care unit stay, and hospital stay; mortality; and frequency and
severity of adverse events. CONCLUSION: Patients receiving a silver-coated
endotracheal tube had a statistically significant reduction in the incidence of
VAP and delayed time to VAP occurrence compared with those receiving a similar,
uncoated tube. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00148642.

2008 Benefits and risks of tight glucose control in critically ill adults: a meta-analysis

JAMA. 2008 Aug 27;300(8):933-44.

Wiener RS, Wiener DC, Larson RJ.

VA Outcomes Group, 111 B, Department of Veterans Affairs Medical Center, White
River Junction, VT 05009, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.

CONTEXT: The American Diabetes Association and Surviving Sepsis Campaign
recommend tight glucose control in critically ill patients based largely on 1
trial that shows decreased mortality in a surgical intensive care unit. Because
similar studies report conflicting results and tight glucose control can cause
dangerous hypoglycemia, the data underlying this recommendation should be
critically evaluated. OBJECTIVE: To evaluate benefits and risks of tight glucose
control vs usual care in critically ill adult patients. DATA SOURCES: MEDLINE
(1950-2008), the Cochrane Library, clinical trial registries, reference lists,
and abstracts from conferences from both the American Thoracic Society
(2001-2008) and the Society of Critical Care Medicine (2004-2008). STUDY
SELECTION: We searched for studies in any language in which adult intensive care
patients were randomly assigned to tight vs usual glucose control. Of 1358
identified studies, 34 randomized trials (23 full publications, 9 abstracts, 2
unpublished studies) met inclusion criteria. DATA EXTRACTION AND ANALYSIS: Two
reviewers independently extracted information using a prespecified protocol and
evaluated methodological quality with a standardized scale. Study investigators
were contacted for missing details. We used both random- and fixed-effects models
to estimate relative risks (RRs). RESULTS: Twenty-nine randomized controlled
trials totaling 8432 patients contributed data for this meta-analysis. Hospital
mortality did not differ between tight glucose control and usual care overall
(21.6% vs 23.3%; RR, 0.93; 95% confidence interval [CI], 0.85-1.03). There was
also no significant difference in mortality when stratified by glucose goal ([1]
very tight: < or = 110 mg/dL; 23% vs 25.2%; RR, 0.90; 95% CI, 0.77-1.04; or [2]
moderately tight: < 150 mg/dL; 17.3% vs 18.0%; RR, 0.99; 95% CI, 0.83-1.18) or
intensive care unit setting ([1] surgical: 8.8% vs 10.8%; RR, 0.88; 95% CI,
0.63-1.22; [2] medical: 26.9% vs 29.7%; RR, 0.92; 95% CI, 0.82-1.04; or [3]
medical-surgical: 26.1% vs 27.0%; RR, 0.95; 95% CI, 0.80-1.13). Tight glucose
control was not associated with significantly decreased risk for new need for
dialysis (11.2% vs 12.1%; RR, 0.96; 95% CI, 0.76-1.20), but was associated with
significantly decreased risk of septicemia (10.9% vs 13.4%; RR, 0.76; 95% CI,
0.59-0.97), and significantly increased risk of hypoglycemia (glucose < or= 40
mg/dL; 13.7% vs 2.5%; RR, 5.13; 95% CI, 4.09-6.43). CONCLUSION: In critically ill
adult patients, tight glucose control is not associated with significantly
reduced hospital mortality but is associated with an increased risk of
hypoglycemia.

2008 Mobilizing patients in the intensive care unit: improving neuromuscular weakness and physical function

JAMA. 2008 Oct 8;300(14):1685-90.

Needham DM.

Division of Pulmonary and Critical Care Medicine, and Department of Physical
Medicine and Rehabilitation, Johns Hopkins University, Baltimore, Maryland 21205,
USA. This email address is being protected from spambots. You need JavaScript enabled to view it.

Early mobilization of patients in the hospital and the intensive care unit has a
strong historical precedent. However, in more recent times, deep sedation and bed
rest have been part of routine medical care for many mechanically ventilated
patients. A growing body of literature demonstrates that survivors of severe
critical illness commonly have significant and prolonged neuromuscular
complications that impair their physical function and quality of life after
hospital discharge. Bed rest, and its associated mechanisms, may play an
important role in the pathogenesis of neuromuscular weakness in critically ill
patients. A new approach for managing mechanically ventilated patients includes
reducing deep sedation and increasing rehabilitation therapy and mobilization
soon after admission to the intensive care unit. Emerging research in this field
provides preliminary evidence supporting the safety, feasibility, and potential
benefits of early mobilization in critical care medicine.