2003 Nosocomial infections in adult intensive-care units

The Lancet, Volume 361, Issue 9374, Pages 2068 - 2077, 14 June 2003 <Previous Article|Next Article>doi:10.1016/S0140-6736(03)13644-6Cite or Link Using DOI

Prof Jean-Louis Vincent MD a

Nosocomial infections affect about 30% of patients in intensive-care units and are associated with substantial morbidity and mortality. Several risk factors have been identified, including the use of catheters and other invasive equipment, and certain groups of patients-eg, those with trauma or burns-are recognised as being more susceptible to nosocomial infection than others. Awareness of these factors and adherence to simple preventive measures, such as adequate hand hygiene, can limit the burden of disease. Management of nosocomial infection relies on adequate and appropriate antibiotic therapy, which should be selected after discussion with infectious-disease specialists and adapted as microbiological data become available.

2003 Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial

The Lancet, Volume 362, Issue 9389, Pages 1011 - 1016, 27 September 2003 <Previous Article|Next Article>doi:10.1016/S0140-6736(03)14409-1Cite or Link Using DOI

Dr Evert de Jonge MD a , Marcus J Schultz MD a, Lodewijk Spanjaard MD b, Prof Patrick MM Bossuyt MD c, Prof Margaretha B Vroom MD a, Prof Jacob Dankert MD b, Jozef Kesecioglu MD d

Selective decontamination of the digestive tract (SDD) is an infection-prevention regimen used in critically ill patients. We assessed the effects of SDD on intensive-care-unit (ICU) and hospital mortality, and on the acquisition of resistant bacteria in adult patients admitted to intensive care
We did a prospective, controlled, randomised, unblinded clinical trial. 934 patients admitted to a surgical and medical ICU were randomly assigned oral and enteral polymyxin E, tobramycin, and amphotericin B combined with an initial 4-day course of intravenous cefotaxime (SDD group n=466), or standard treatment (controls n=468). Primary endpoints were ICU and hospital mortality and the acquisition of resistant bacteria.
In the SDD group 69 (15%) patients died in the ICU compared with 107 (23%) in the control group (p=0·002). Hospital mortality was lower in the SDD groups than in the control group (113 [24%] vs 146 [31%], p=0·02). During their stay in intensive care, colonisation with gram-negative bacteria resistant to ceftazidime, ciprofloxacin, imipenem, polymyxin E, or tobramycin occurred in 61 (16%) of 378 SDD patients and in 104 (26%) of 395 patients in the control group (p=0·001). Colonisation with vancomycin-resistant enterococcus occurred in five (1%) SDD patients and in four (1%) controls (p=1·0). No patient in either group was colonised with meticillin-resistant Staphylococcus aureus.
In a setting with low prevalence of vancomycin-resistant enterococcus and meticillin-resistant S aureus, SDD can decrease ICU and hospital mortality and colonisation with resistant gram-negative aerobic bacteria.

2003 Herpes simplex virus in the respiratory tract of critical care patients: a prospective study

The Lancet, Volume 362, Issue 9395, Pages 1536 - 1541, 8 November 2003

Dr Peggy Bruynseels MD a , Prof Philippe G Jorens MD b, Hendrik E Demey b, Prof Herman Goossens MD a, Prof Stefaan R Pattyn MD a, Monique M Elseviers PhD a, Prof Joost Weyler MD d, Prof Leo L Bossaert MD b, Yves Mentens MD c, Prof Margareta Ieven PhD a


Herpes simplex virus (HSV) is occasionally detected in the lower respiratory tract of patients in intensive care, but its clinical importance in such situations remains unclear. We did a prospective cohort study to define the prevalence, origin, risk factors, and clinical relevance of HSV in the respiratory tract of patients undergoing critical care.
We tested 764 patients admitted to intensive care for the presence of HSV in the respiratory tract, and assessed statistical relations between this virus and clinical variables.
HSV was detected by oropharyngeal swab in the upper respiratory tract of 169 (22%) of 764 patients, within 10 days of admission for 150 (89%) of these individuals. The virus was isolated in 58 (16%) of 361 patients whose lower respiratory tract was sampled. The presence of HSV in the throat was a risk factor for development of HSV infections in the lower respiratory tract (p < 0·001). HSV was isolated most frequently in patients with severe disease. HSV in the throat was associated with acute respiratory distress syndrome (p < 0·001) and with increased length of stay in intensive care (p < 0·001).
Our data suggest that HSV reactivation or infection of the upper respiratory tract is frequent among patients in intensive care, and is a risk factor for development of lower respiratory tract infection with this virus, possibly by means of aspiration.

2004 Improving care of the critically ill: institutional and health-care system approaches

The Lancet, Volume 363, Issue 9417, Pages 1314 - 1320, 17 April 2004

Dr Derek C Angus MD a , Nick Black MD b


Institutional and health-care system approaches complement bedside strategies to improve care of the critically ill. Focusing on the USA and the UK, we discuss seven approaches: education (especially of non-clinical managers, policy-makers, and the public), organisational guidelines, performance reporting, financial and sociobehavioural incentives to health-care professionals and institutions, regulation, legal requirements, and health-care system reorganisation. No single action is likely to have sustained effect and we recommend a combination of approaches. Several recent initiatives that hold promise tie performance reporting to financial incentives. Though performance reporting has been hampered by concerns over cost and accuracy, it remains an essential component and we recommend continued effort in this area. We also recommend more public education and use of organisational guidelines, such as admission criteria and staffing levels in intensive care units. Even if these endeavours are successful, with rising demand for services and continuing pressure to control costs, optimum care of the critically ill will not be realised without a fundamental reorganisation of services. In both the USA and UK, we recommend exploration of regionalised care, akin to US state trauma systems, and greater use of physician-extenders, such as nurse practitioners, to provide enhanced access to specialist care for critical illness.
This article is the last in a series of five focusing on improving care and safety of the critically ill. Previous articles introduced the concepts of critical illness, quality of care, and patients' safety1 and reviewed approaches to identify patients' safety concerns,2 measure quality of care,3 and improve care through modification of caregiver behaviour.4 Three themes emerged: care of the critically ill is fraught with potential hazards for patients; errors of omission (ie, failure to provide contemporary, evidence-based care) might be a greater threat to patients' safety than errors of commission; and improvement of care needs the appropriate cultural milieu, a system-wide commitment, active engagement of all relevant stakeholders, and constant measurement and feedback.

2005 Septic shock

The Lancet, Volume 365, Issue 9453, Pages 63 - 78, 1 January 2005

Prof Djillali Annane MD a , Prof Eric Bellissant MD b, Jean-Marc Cavaillon PhD c


Septic shock, the most severe complication of sepsis, is a deadly disease. In recent years, exciting advances have been made in the understanding of its pathophysiology and treatment. Pathogens, via their microbial-associated molecular patterns, trigger sequential intracellular events in immune cells, epithelium, endothelium, and the neuroendocrine system. Proinflammatory mediators that contribute to eradication of invading microorganisms are produced, and anti-inflammatory mediators control this response. The inflammatory response leads to damage to host tissue, and the anti-inflammatory response causes leucocyte reprogramming and changes in immune status. The time-window for interventions is short, and treatment must promptly control the source of infection and restore haemodynamic homoeostasis. Further research is needed to establish which fluids and vasopressors are best. Some patients with septic shock might benefit from drugs such as corticosteroids or activated protein C. Other therapeutic strategies are under investigation, including those that target late proinflammatory mediators, endothelium, or the neuroendocrine system.

2005 Introduction of the medical emergency team (MET) system: a cluster-randomised controlled trial

The Lancet, Volume 365, Issue 9477, Pages 2091 - 2097, 18 June 2005

MERIT study investigators ‡


Patients with cardiac arrests or who die in general wards have often received delayed or inadequate care. We investigated whether the medical emergency team (MET) system could reduce the incidence of cardiac arrests, unplanned admissions to intensive care units (ICU), and deaths.
We randomised 23 hospitals in Australia to continue functioning as usual (n=11) or to introduce a MET system (n=12). The primary outcome was the composite of cardiac arrest, unexpected death, or unplanned ICU admission during the 6-month study period after MET activation. Analysis was by intention to treat.
Introduction of the MET increased the overall calling incidence for an emergency team (3·1 vs 8·7 per 1000 admissions, p=0·0001). The MET was called to 30% of patients who fulfilled the calling criteria and who were subsequently admitted to the ICU. During the study, we recorded similar incidence of the composite primary outcome in the control and MET hospitals (5·86 vs 5·31 per 1000 admissions, p=0·640), as well as of the individual secondary outcomes (cardiac arrests, 1·64 vs 1·31, p=0·736; unplanned ICU admissions, 4·68 vs 4·19, p=0·599; and unexpected deaths, 1·18 vs 1·06, p=0·752). A reduction in the rate of cardiac arrests (p=0·003) and unexpected deaths (p=0·01) was seen from baseline to the study period for both groups combined.
The MET system greatly increases emergency team calling, but does not substantially affect the incidence of cardiac arrest, unplanned ICU admissions, or unexpected death.

2005 Assessment of the clinical effectiveness of pulmonary artery catheters in management of patients in intensive care (PAC-Man): a randomised controlled trial

The Lancet, Volume 366, Issue 9484, Pages 472 - 477, 6 August 2005

Sheila Harvey MSc a, David A Harrison PhD a, Prof Mervyn Singer FRCP b , Joanne Ashcroft RGN a, Carys M Jones BSc a, Diana Elbourne PhD c, William Brampton FRCA d, Dewi Williams FRCA e, Duncan Young DM f, Kathryn Rowan DPhil a, on behalf of the PAC-Man study collaboration‡


Over the past 30 years the pulmonary artery catheter (PAC) has become a widely used haemodynamic monitoring device in the management of critically ill patients, though doubts exist about its safety. Our aim was, therefore, to ascertain whether hospital mortality is reduced in critically ill patients when they are managed with a PAC.
We did a randomised controlled trial to which we enrolled 1041 patients from 65 UK intensive care units. We assigned individuals to management with (n=519) or without (n=522) a PAC. The timing of insertion and subsequent clinical management were at the discretion of the treating clinician. Intensive care units decided a priori to have the option of using an alternative cardiac output-monitoring device in control patients.
1014 patients were eligible for analysis. We noted no difference in hospital mortality between patients managed with or without a PAC (68% [346 of 506] vs 66% [333 of 507], p=0·39; adjusted hazard ratio 1·09, 95% CI 0·94-1·27). We noted complications associated with insertion of a PAC in 46 of 486 individuals in whom the device was placed, none of which was fatal.
Our findings indicate no clear evidence of benefit or harm by managing critically ill patients with a PAC. Efficacy studies are needed to ascertain whether management protocols involving PAC use can result in improved outcomes in specific groups if these devices are not to become a redundant technology.

2008 Perioperative β blockers in patients having non-cardiac surgery: a metaanalysis

The Lancet, Volume 372, Issue 9654, Pages 1962 - 1976, 6 December 2008

Perioperative β blockers in patients having non-cardiac surgery: a meta-analysis




American College of Cardiology and American Heart Association (ACC/AHA) guidelines on perioperative assessment recommend perioperative β blockers for non-cardiac surgery, although results of some clinical trials seem not to support this recommendation. We aimed to critically review the evidence to assess the use of perioperative β blockers in patients having non-cardiac surgery.


We searched Pubmed and Embase for randomised controlled trials investigating the use of β blockers in non-cardiac surgery. We extracted data for 30-day all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, heart failure, and myocardial ischaemia, safety outcomes of perioperative bradycardia, hypotension, and bronchospasm.


33 trials included 12 306 patients. β blockers were not associated with any significant reduction in the risk of all-cause mortality, cardiovascular mortality, or heart failure, but were associated with a decrease (odds ratio [OR] 0·65, 95% CI 0·54—0·79) in non-fatal myocardial infarction (number needed to treat [NNT] 63) and decrease (OR 0·36, 0·26—0·50) in myocardial ischaemia (NNT 16) at the expense of an increase (OR 2·01, 1·27—3·68) in non-fatal strokes (number needed to harm [NNH] 293). The beneficial effects were driven mainly by trials with high risk of bias. For the safety outcomes, β blockers were associated with a high risk of perioperative bradycardia requiring treatment (NNH 22), and perioperative hypotension requiring treatment (NNH 17). We recorded no increased risk of bronchospasm.


Evidence does not support the use of β-blocker therapy for the prevention of perioperative clinical outcomes in patients having non-cardiac surgery. The ACC/AHA guidelines committee should soften their advocacy for this intervention until conclusive evidence is available.

2006 Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial

Lancet. 2006 Jul 29;368(9533):379-85.

Vinsonneau C, Camus C, Combes A, Costa de Beauregard MA, Klouche K, Boulain T,
Pallot JL, Chiche JD, Taupin P, Landais P, Dhainaut JF; Hemodiafe Study Group.

Department of Intensive Care, Cochin Port-Royal University Hospital, René
Descartes University, Paris, France. This email address is being protected from spambots. You need JavaScript enabled to view it.

BACKGROUND: Whether continuous renal replacement therapy is better than
intermittent haemodialysis for the treatment of acute renal failure in critically
ill patients is controversial. In this study, we compare the effect of
intermittent haemodialysis and continuous venovenous haemodiafiltration on
survival rates in critically ill patients with acute renal failure as part of
multiple-organ dysfunction syndrome. METHODS: Our prospective, randomised,
multicentre study took place between Oct 1, 1999, and March 3, 2003, in 21
medical or multidisciplinary intensive-care units from university or community
hospitals in France. Guidelines were provided to achieve optimum haemodynamic
tolerance and effectiveness of solute removal in both groups. The two groups were
treated with the same polymer membrane and bicarbonate-based buffer. 360 patients
were randomised, and the primary endpoint was 60-day survival based on an
intention-to-treat analysis. FINDINGS: Rate of survival at 60-days did not differ
between the groups (32% in the intermittent haemodialysis group versus 33% in the
continuous renal replacement therapy group [95 % CI -8.8 to 11.1,]), or at any
other time. INTERPRETATION: These data suggest that, provided strict guidelines
to improve tolerance and metabolic control are used, almost all patients with
acute renal failure as part of multiple-organ dysfunction syndrome can be treated
with intermittent haemodialysis.

2007 12-h pretreatment with methylprednisolone versus placebo for prevention of postextubation laryngeal oedema: a randomised double-blind trial

Lancet. 2007 Mar 31;369(9567):1083-9.

François B, Bellissant E, Gissot V, Desachy A, Normand S, Boulain T, Brenet O,
Preux PM, Vignon P; Association des Réanimateurs du Centre-Ouest (ARCO).

Medical-Surgical Intensive Care Unit, Dupuytren Teaching hospital, Limoges,

BACKGROUND: The efficacy of corticosteroids in reducing the incidence of
postextubation laryngeal oedema is controversial. We aimed to test our hypothesis
that methylprednisolone started 12 h before a planned extubation could prevent
postextubation laryngeal oedema. METHODS: We did a placebo-controlled,
double-blind multicentre trial in 761 adults in intensive-care units. Patients
who were ventilated for more than 36 h and underwent a planned extubation
received intravenous 20 mg methylprednisolone (n=380) or placebo (381) 12 h
before extubation and every 4 h until tube removal. The primary endpoint was
occurrence of laryngeal oedema within 24 h of extubation. Laryngeal oedema was
clinically diagnosed and deemed serious if tracheal reintubation was needed.
Analyses were done on a per protocol and intention-to-treat basis. This trial is
registered at ClinicalTrials.gov, number NCT00199576. FINDINGS: 63 patients could
not be assessed, mainly because of self-extubation (n=16) or cancelled extubation
(44) between randomisation and planned extubation. 698 patients were analysed
(343 in placebo group, 355 in methylprednisolone group). Methylprednisolone
significantly reduced the incidence of postextubation laryngeal oedema (11 of
355, 3%vs 76 of 343, 22%, p<0.0001), the global incidence of reintubations (13 of
355, 4%vs 26 of 343, 8%, p=0.02), and the proportion of reintubations secondary
to laryngeal oedema (one of 13, 8 %vs 14 of 26, 54%, p=0.005). One patient in
each group died after extubation, and atelectasia occurred in one patient given
methylprednisolone. INTERPRETATION: Methylprednisolone started 12 h before a
planned extubation substantially reduced the incidence of postextubation
laryngeal oedema and reintubation. Such pretreatment should be considered in
adult patients before a planned extubation that follows a tracheal intubation of
more than 36 h.

2007 Acute lung injury and the acute respiratory distress syndrome: a clinical review

Lancet. 2007 May 5;369(9572):1553-64.

Wheeler AP, Bernard GR.

Medical Intensive Care Unit, Vanderbilt University Medical Center, Nashville, TN
37232-2650, USA.

Acute respiratory distress syndrome and acute lung injury are well defined and
readily recognised clinical disorders caused by many clinical insults to the lung
or because of predispositions to lung injury. That this process is common in
intensive care is well established. The mainstay of treatment for this disorder
is provision of excellent supportive care since these patients are critically ill
and frequently have coexisting conditions including sepsis and multiple organ
failure. Refinements in ventilator and fluid management supported by data from
prospective randomised trials have increased the methods available to effectively
manage this disorder.

2007 Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial

Lancet. 2007 Aug 25;370(9588):676-84.

Erratum in:
    Lancet. 2007 Sep 22;370(9592):1034.

Annane D, Vignon P, Renault A, Bollaert PE, Charpentier C, Martin C, Troché G,
Ricard JD, Nitenberg G, Papazian L, Azoulay E, Bellissant E; CATS Study Group.

Raymond Poincaré Hospital (AP-HP), University of Versailles Saint Quentin, PRES
UniverSud, Paris, France. This email address is being protected from spambots. You need JavaScript enabled to view it.

BACKGROUND: International guidelines for management of septic shock recommend
that dopamine or norepinephrine are preferable to epinephrine. However, no large
comparative trial has yet been done. We aimed to compare the efficacy and safety
of norepinephrine plus dobutamine (whenever needed) with those of epinephrine
alone in septic shock. METHODS: This prospective, multicentre, randomised,
double-blind study was done in 330 patients with septic shock admitted to one of
19 participating intensive care units in France. Participants were assigned to
receive epinephrine (n=161) or norepinephrine plus dobutamine (n=169), which were
titrated to maintain mean blood pressure at 70 mm Hg or more. The primary outcome
was 28-day all-cause mortality. Analyses were by intention to treat. This trial
is registered with ClinicalTrials.gov, number NCT00148278. FINDINGS: There were
no patients lost to follow-up; one patient withdrew consent after 3 days. At day
28, there were 64 (40%) deaths in the epinephrine group and 58 (34%) deaths in
the norepinephrine plus dobutamine group (p=0.31; relative risk 0.86, 95% CI
0.65-1.14). There was no significant difference between the two groups in
mortality rates at discharge from intensive care (75 [47%] deaths vs 75 [44%]
deaths, p=0.69), at hospital discharge (84 [52%] vs 82 [49%], p=0.51), and by day
90 (84 [52%] vs 85 [50%], p=0.73), time to haemodynamic success (log-rank
p=0.67), time to vasopressor withdrawal (log-rank p=0.09), and time course of
SOFA score. Rates of serious adverse events were also similar. INTERPRETATION:
There is no evidence for a difference in efficacy and safety between epinephrine
alone and norepinephrine plus dobutamine for the management of septic shock.

2008 Induced hypothermia and fever control for prevention and treatment of neurological injuries

Lancet. 2008 Jun 7;371(9628):1955-69.

Polderman KH.

Department of Intensive Care, University Medical Center Utrecht, Utrecht,
Netherlands. This email address is being protected from spambots. You need JavaScript enabled to view it.

Increasing evidence suggests that induction of mild hypothermia (32-35 degrees C)
in the first hours after an ischaemic event can prevent or mitigate permanent
injuries. This effect has been shown most clearly for postanoxic brain injury,
but could also apply to other organs such as the heart and kidneys. Hypothermia
has also been used as a treatment for traumatic brain injury, stroke, hepatic
encephalopathy, myocardial infarction, and other indications. Hypothermia is a
highly promising treatment in neurocritical care; thus, physicians caring for
patients with neurological injuries, both in and outside the intensive care unit,
are likely to be confronted with questions about temperature management more
frequently. This Review discusses the available evidence for use of controlled
hypothermia, and also deals with fever control. Besides discussing the evidence,
the aim is to provide information to help guide treatments more effectively with
regard to timing, depth, duration, and effective management of side-effects. In
particular, the rate of rewarming seems to be an important factor in establishing
successful use of hypothermia in the treatment of neurological injuries.

2006 Alcohol abuse in the critically ill patient

Lancet. 2006 Dec 23;368(9554):2231-42.

Moss M, Burnham EL.

Divison of Pulmonary Sciences and Critical Care Medicine, University of Colorado
at Denver and Health Sciences Center, Denver, CO 80262, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.

Alcohol abuse and dependence disorders are common in the 10% of hospitalised
patients who need admission to the intensive care unit (ICU), but these disorders
are often undiagnosed. The systemic effects from the excessive use of alcohol
increase susceptibility to, or directly cause various important disorders in the
critically ill. Early recognition of alcohol abuse and dependence is necessary
and should prompt consideration of several alcohol-specific diagnoses that have
important prognostic and therapeutic implications for these patients. We discuss
the use of screening tests to improve the identification of alcohol abuse and
dependence disorders, the epidemiology and pathogenesis of important
alcohol-related disorders, differences in the presentation of several common
alcohol-related diagnoses in the ICU, and important alcohol-specific therapies.