Critical Care Journal Scan, 2005 Year in Review

Greg S. Martin, MD, MSc


February 13, 2006

Editor's Note:
In place of our usual Journal Scan, we present a review of 10 important articles in critical care medicine. Here are summaries of some important findings from
Annals of Internal Medicine, Critical Care Medicine, The New England Journal of Medicine, and other important journals. Links to the article abstracts are also provided. (Access to full-text articles usually requires registration at the specific journal's Web site.)

The New England Journal of Medicine
January 2005 (Volume 352, Number 4)

Probable Person-to-Person Transmission of Avian Influenza A (H5N1)

Ungchusak K, Auewarakul P, Dowell SF, et al
N Engl J Med. 2005;352:333-340

A highly pathogenic strain of influenza arose in 2004 to cause significant morbidity and mortality primarily in Asia. This strain (H5N1) caused disease in chickens and was then recognized to cause human disease in the transmission from infected fowl.[1] The disease was highly fatal and transmission patterns were incompletely known at the time. The spread of this disease across many of the less developed and poultry-producing countries of Asia led to mass culling of fowl in order to prevent spread of the disease. Because of the pathogenic nature of this strain and its potential to cause human deaths, great concern arose about the ability of this strain to transmit from one person to another.

This landmark article described the clinical and epidemiologic features of the disease as it appeared to transmit from one person to another, with combined epidemiologic and laboratory data. An index patient, an 11-year-old girl from Thailand, became ill with a viral respiratory illness 3-4 days after exposure to dying chickens. She was hospitalized shortly thereafter and subsequently died. Her disease was confirmed to be H5N1 avian influenza. Her 26-year-old mother traveled from another province to care for her daughter in the hospital, providing unprotected nursing care. She was without prior exposure to poultry and became ill 3-4 days after caring for her daughter. She was subsequently hospitalized and died. Her disease was confirmed to be H5N1 avian influenza. The index patient's aunt also provided unprotected nursing care to her and subsequently was hospitalized with a viral respiratory illness. She was diagnosed with H5N1 avian influenza and recovered with oseltamivir treatment. Because the secondary cases of H5N1 avian influenza did not have prior exposure to poultry and because the time course of their disease fit with exposure to the index patient, it was concluded that they contracted the disease through person-to-person transmission.

This case is the primary example of concern for public health authorities worldwide. Because fowl can become infected and remain in areas of public exposure and even migrate worldwide, the potential for spread is tremendous. Through August 2005, there had been 112 confirmed cases and 57 deaths (fatality rate = 51%), as reported in a review in The New England Journal of Medicine.[2] More recently, H5N1 avian influenza has moved across Asia and into Eastern Europe, with continued transmission from birds to humans.[3]

H5N1 avian influenza remains one of the top infectious disease and public health concerns worldwide. Because H5N1 avian influenza frequently causes respiratory distress and significant other organ dysfunction, it carries the potential for creating a crisis in the provision of intensive care. Health officials from around the world are critically considering the methods for providing adequate patient (and particularly critical) care in the event of a global pandemic.[4]


  1. Li KS, Guan Y, Wang J, et al. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature. 2004;430:209-213.

  2. Beigel JH, Farrar J, Han AM, et al. Avian influenza A (H5N1) infection in humans. N Engl J Med. 2005;353:1374-1385.

  3. World Health Organization. Avian Influenza. Available at: Accessed February 8, 2006.

  4. Centers for Disease Control and Prevention. Avian Influenza. Available at: Accessed February 8, 2006.


October 20, 2005 (Volume 353, Number 16)

Incidence and Outcomes of Acute Lung Injury

Rubenfeld GD, Caldwell E, Peabody E, et al
N Engl J Med. 2005;353:1685-1693

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are 2 feared and potentially lethal forms of respiratory failure. They occur in critically ill patients who develop alterations in pulmonary vascular permeability leading to the accumulation of proteinaceous edema. There is even a clinically applicable international consensus definition that allows us to identify patients with these conditions.[1] However, there has continued to be debate about how frequently these conditions occur.

Original estimates of ALI/ARDS incidence estimated 150,000 cases per year in the United States.[1] However, this estimate was based on crude and fundamentally anecdotal evidence. Subsequent population-based studies found wide variations in incidence, presumably because of the population studied. In certain areas where causes of ALI and ARDS are less common, the incidence may be less than 5 per 100,000 person-years.[2,3] However, nearly all other estimates have shown higher incidences of ALI/ARDS.[4,5,6]

The authors of this study sought to determine an accurate population-based incidence of ALI and ARDS by capturing all cases within a defined population center. They used the area of Seattle, Washington, and conducted the King County Lung Injury Project (KCLIP) during a 12-month period. They screened patients from intensive care units (ICUs) in all hospitals and used the American-European Consensus Conference definition[1] for defining ALI and ARDS. Based on this study, the incidence of ALI was 80 cases per 100,000 person-years, with an associated inhospital mortality rate of 38%. The incidence of ALI increased with age, as did mortality. Approximately 75% of identified patients met the more severe hypoxemia criteria for ARDS.

This complex and well conducted study provides the first reliable estimate of ALI in the United States. While some of the findings are not novel or surprising (such as sepsis being the most common cause of ALI), it provides important epidemiologic information about the frequency of this disease. In fact, this study shows that the number of people who die with ALI is similar to the number of people who die with breast cancer or HIV each year. Perhaps even more important, an even larger number of survivors with ALI suffer from reduced quality of life because of having developed this condition.[7] The primary finding of this study is an unfortunately accurate assessment of the frequency of this disease, showing that ALI is more common than previously thought and affects a large number of lives each year.


  1. Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;149:818-824.

  2. Villar J, Slutsky AS. The incidence of the adult respiratory distress syndrome. Am Rev Respir Dis. 1989;140:814-816.

  3. Thomsen GE, Morris AH. Incidence of the adult respiratory distress syndrome in the state of Utah. Am J Respir Crit Care Med. 1995;152:965-971.

  4. Luhr OR, Antonsen K, Karlsson M, et al. Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. Am J Respir Crit Care Med. 1999;159:1849-1861.

  5. Bersten AD, Edibam C, Hunt T, Moran J; Australian and New Zealand Intensive Care Society Clinical Trials Group. Incidence and mortality of acute lung injury and the acute respiratory distress syndrome in three Australian States. Am J Respir Crit Care Med. 2002;165:443-448.

  6. Artigas A, Bernard GR, Carlet J, et al. The American-European Consensus Conference on ARDS, part 2: ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling. Am J Respir Crit Care Med. 1998;157(4 Pt 1):1332-1347.

  7. Herridge MS, Cheung AM, Tansey CM, et al; Canadian Critical Care Trials Group. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003;348:683-693.


August 17, 2005 (Volume 294, Number 7)

Acute Renal Failure in Critically Ill Patients: A Multinational, Multicenter Study

Uchino S, Kellum JA, Bellomo R, et al
JAMA. 2005;294:813-818

The frequency of acute renal failure (ARF) in critically ill patients is poorly understood, and information regarding relevant clinical outcomes for these patients is limited. In particular, almost all information regarding this condition is from a single center or small geographic region.[1,2,3,4,5,6] There is very little information on ARF from multiple countries or the contributing causes and prognostic factors in a large cohort of patients. The authors of this study sought to determine the prevalence of ARF in ICU patients across multiple countries and to characterize differences in etiology of illness severity in clinical practice while also collecting information that would help to determine the association of these variables with important patient outcomes.

This was a multinational, prospective, observational study of ICU patients from 54 centers in 23 countries across Australia, Asia, Europe, and North and South America. The researchers identified approximately 30,000 critically ill adult and adolescent patients, of which 5.7% developed ARF during their ICU stay. ARF was defined as the need for renal replacement therapy or oliguria with less than 200 mL of urine output over 12 hours or marked azotemia with a blood urea nitrogen level > 84 mg/dL. A total of 30% of patients had pre-existing renal dysfunction, and the most common contributing factor to ARF was septic shock (approximately 50% of patients). Besides septic shock, other major contributing factors to the development of ARF included major surgery, cardiogenic shock, hypokalemia, and drug-induced renal failure. Independent risk factors for hospital mortality included the receipt of vasopressor agents, mechanical ventilation, and the diagnoses of septic shock, cardiogenic shock, and hepatorenal syndrome. Overall hospital mortality was 60%, and dialysis dependence at hospital discharge among survivors was approximately 15%.

This study adds substantially to the existing body of literature regarding the epidemiology of ARF in the ICU. Previous studies have found the prevalence of this condition to be between 1% and 25%, which is a nearly identical range to that observed in this study when analyzed according to individual study sites. Among the variety of conditions identify that may cause ARF, a large proportion are amenable to medical intervention. For instance, interventions may be applied to major surgery to reduce the occurrence of ARF. Similarly, drug-induced and hypovolemia-induced ARF could be avoided with appropriate interventions. While this study may not directly impact clinical practice, it does lay the groundwork for future studies where interventions may be put in place. It also helps physicians understand the factors that may lead to the development of ARF and the expected outcomes thereafter.


  1. Turney JH, Harshall DH, Brownjohn AM, et al. The evolution of acute renal failure, 1956-1988. Q J Med. 1990;74:83-104.

  2. Schaefer JH, Jochimsen F, Keller F, et al. Outcome prediction of acute renal failure in medical intensive care. Intensive Care Med. 1991;17:19-24.

  3. Chertow GM, Christiansen CL, Cleary PD, et al. Prognostic stratification in critically ill patients with acute renal failure requiring dialysis. Arch Intern Med. 1995;155:1505-1511.

  4. Parker RA, Himmelfarb J, Tolkoff-Rubin N, et al. Prognosis of patients with acute renal failure requiring dialysis. Am J Kidney Dis. 1998;32:432-443.

  5. Silvester W, Bellomo R, Cole L. Epidemiology, management, and outcome of severe acute renal failure of critical illness in Australia. Crit Care Med. 2001;29:1910-1915.

  6. Mehta RL, Pascual MT, Gruta CG, et al. Refining predictive models in critically ill patients with acute renal failure. J Am Soc Nephrol. 2002;13:1350-1357.


October 5, 2005 (Volume 294, Number 13)

Impact of the Pulmonary Artery Catheter in Critically Ill Patients: Meta-analysis of Randomized Clinical Trials

Shah MR, Haselblad V, Stevenson LW, et al
JAMA. 2005;294:1664-1670

Placement of a pulmonary artery catheter (PAC) is a frequent approach to hemodynamic monitoring in hospitalized patients. Approximately 1.5 million PACs are used each year in the United States, and their use is broadly spread across patients undergoing diagnostic catheterization, high-risk surgery, or experiencing major critical illnesses. Physicians have been able to place the pulmonary artery balloon flotation catheter at the bedside since the 1970s.[1] However, there has been little development in proving its ability to provide outcome-enhancing information for guiding therapy and even in confirming the safety of its use.

Initial studies questioning the safety of PACs almost invariably found them to be associated with a higher risk of death. However, these studies were complicated by the fact that patients who underwent PAC placement were more severely ill and therefore more likely to die regardless of the catheter. However, powerful statistical methods were described as being capable of alleviating this problem. In 1996, Connors and colleagues published the seminal article questioning the safety of the PAC in critically ill patients.[2] In this study, they examined a large number of critically ill patients and matched those who received a PAC with a similar patient who did not receive a PAC. In this way, by a complex matching strategy, they tried to eliminate the bias of placing PACs in patients who were more likely to die. After matching by this "propensity score," patients who underwent PAC placement were significantly more likely to die than those who did not receive a PAC.

Since that publication, a number of controlled, clinical trials have been conducted to examine the effect of the PAC on patient-centered clinical outcomes. The Sandham study found that high-risk surgical patients who underwent PAC placement were no more likely to die than non-PAC patients, but they did experience higher rates of pulmonary embolic events.[3] Most recently, the ESCAPE trial reported that use of the PAC in managing severe congestive heart failure patients did not expedite recovery or improve survival, and patients who underwent PAC placement were twice as likely to experience adverse events.[4] In general trials of critically ill patients, there is no evidence that PAC use improves outcomes. In trials where therapy is not controlled, PAC use is generally associated with greater fluid administration and may be associated with an increased rate of adverse events such as renal failure or thrombocytopenia.[5] Among critically ill patients with specific conditions, such as with shock and ALI, there is no difference in outcomes according to use of the PAC.[6]

The data from this study confirm what has been shown in a variety of controlled, clinical trials: clinical outcomes are not improved by the use of the PAC in critically ill patients. However, catheter-related complications and adverse events are more common in patients who undergo PAC placement. Taking these findings into account, it is difficult to justify routine use of the PAC in critically ill patients.


  1. Swan HJ, Ganz W, Forrester J. Catheterization of the heart in man with use of a flow-directed balloon- tipped catheter. N Engl J Med. 1970;283:447-451.

  2. Connors AF Jr, Speroff T, Dawson NV, et al. The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT Investigators. JAMA. 1996;276:889-897.

  3. Sandham JD, Hull RD, Brant RF, et al. A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients. N Engl J Med. 2003;348:5-14.

  4. Binanay C, Califf RM, Hasselblad V, et al. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial. JAMA. 2005;294:1625-1633.

  5. Rhodes A, Cusack RJ, Newman PJ, Grounds RM, Bennett ED. A randomised, controlled trial of the pulmonary artery catheter in critically ill patients. Intensive Care Med. 2002;28:256-264.

  6. Richard C, Warszawski J, Anguel N, et al. Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2003;290:2713-2720.


Critical Care Medicine
January 2005 (Volume 33, Number 1)

Invasive Approaches to the Diagnosis of Ventilator-Associated Pneumonia: A Meta-Analysis

Shorr AF, Sherner JH, Jackson WL, Kollef MH
Crit Care Med. 2005;33:46-53

Ventilator-associated pneumonia (VAP) is a common condition in the ICU that results in directly attributable morbidity and mortality with prolongation of intensive care and hospital length of stay.[1,2] "Bundles" have been developed that can effectively prevent VAP when uniformly applied. These prophylactic strategies are becoming common in ICUs around the world. However, to date, there continues to be significant controversy regarding the diagnosis and management of VAP. For instance, physicians continue to disagree about the best strategy for diagnosing VAP, with a common standard being the microbiological examination of endotracheal aspirate specimens, as compared with invasive or noninvasive bronchoalveolar lavage or other protected microbiological specimens. The diagnosis of VAP is important because it has significant impact on antibiotic prescribing and subsequent resistance patterns, as well as cost of hospital care and resource utilization.

In this study, the authors sought to determine whether an invasive diagnostic strategy for VAP would alter antibiotic prescribing and clinical outcomes. To answer those questions, they performed a systemic review (a meta-analysis) of clinical data from patients who underwent invasive diagnostic testing and outcomes assessment. There were 4 randomized, controlled trials of 628 patients, in which VAP was confirmed in 44% to 69% of subjects. Pseudomonas aeruginosa and Staphylococcus aureus were the most common pathogens. The use of an invasive diagnostic strategy did not alter mortality for VAP patients, but it did affect antimicrobial use. Patients managed in this way were approximately 3 times more likely to have a change in antibiotic prescription. Five cohort studies of 635 VAP patients confirmed that invasive microbiological sampling resulted in a change in antibiotic use in more than 50% of patients.

The authors concluded that invasive diagnostic strategies for VAP do not appear to impact clinical outcomes, but they do influence antibiotic prescribing. This conclusion is tempered by the fact that the majority of data from this conclusion comes from a large single trial, thus influencing the overall results.[3] However, this information is relevant for a variety of reasons. Physicians who care for VAP patients would like to improve clinical outcomes for their patients (eg, survival), making any difference in antibiotic prescribing less relevant. In a practical sense, if performing an invasive test does not benefit the patient in the short- or long-term, why perform the test? However, there is important information missing from this study. We do not know whether VAP patients managed with an invasive strategy derived any alternative benefit from the intervention. For example, they may have experienced a reduction in the duration of mechanical ventilation, a lower risk for subsequent resistant nosocomial infections, or lower healthcare costs with similar outcomes. These would all be considered relevant, but we do not know whether this may have occurred.

There are data showing that patients managed with an invasive diagnostic strategy can be safely treated with a shorter duration of antibiotic therapy (8 days vs 15 days), resulting in less antibiotic use overall and a lower risk for subsequent resistant infections if a recurrent infection occurred.[4] Of note, the safety of shortening the duration of antibiotic therapy was not confirmed for patients with pneumonia from P aeruginosa. Even if an invasive diagnostic strategy does not clearly benefit individual patients, it may have benefits to an institution or more global concerns. For instance, given that VAP is a nosocomial infection and the flora causing these infections are locally determined by antibiotic pressure, it may be that altering antibiotic prescription will impact VAP rates and even clinical outcomes by reducing the proportion of infections that result from multiply-resistant organisms.


  1. Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med. 2002;165:867-903.

  2. Heyland DK, Cook DJ, Griffith L, Keenan SP, Brun-Buisson C. The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient. Am J Respir Crit Care Med. 1999;159(4 Pt 1):1249-1256.

  3. Fagon JY, Chastre J, Wolff M, et al. Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia. A randomized trial. Ann Intern Med. 2000;132:621-630.

  4. Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs. 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003;290:2588-2598.


September 2005 (Volume 33, Number 9)

Fluconazole Prophylaxis in Critically Ill Surgical Patients: A Meta-Analysis

Shorr AF, Chung K, Jackson WL, Waterman PE, Kollef MH
Crit Care Med. 2005;33:1928-1935

Fungemia, of which the most common organism is Candida, is a growing problem in ICUs worldwide.[1,2,3] The incidence has increased exponentially, and organisms are more frequently non-albicansCandida species than previously.[1,2] Patients at the highest risk for fungal infections are those who are neutropenic or oncology patients, and among the critically ill are those patients who have undergone surgery. The incidence of fungemia in surgical ICU patients approaches 10 cases per 1000 admissions.[2] Mortality rates with fungemia vary from 25% to 50%, and the directly attributable mortality with fungemia may be as high as 30%.[1,2,3] Regardless, there have been a number of strategies employed in an attempt to reduce the incidence of fungal infections in critically ill patients. One of those is fluconazole prophylaxis; the authors of this study sought to determine if that strategy would decrease the incidence of fungal infections or alter mortality specifically in critically ill surgical patients.

This article is a systematic review of clinical trials involving fluconazole prophylaxis in surgical critical care patients. The authors identified 4 randomized studies involving 626 patients who were randomized to receive either prophylaxis or placebo. Based on these data, fluconazole administration reduced the incidence of fungal infections by over 50% (odds ratio = 0.44) but was not associated with any difference in mortality (odds ratio, 0.87; 95% confidence interval, 0.59-1.28). In addition, fluconazole prophylaxis did not alter the rate of candidemia. Based on these data, the authors concluded that prophylactic fluconazole administration successfully reduces the rate of fungal infections but does not improve survival.

Because fungal infections and fungemia specifically are increasing in incidence and carry a very high mortality, additional strategies should be investigated for improving outcomes with these conditions. The nature of meta-analyses to aggregate data from heterogeneous clinical trials may obscure a clinical benefit for certain subsets (Candida albicans, specific surgical patient types, certain severity of illnesses, or other known risk factors for candidemia such as gut dysfunction). In addition, it is possible that fluconazole prophylaxis does, in fact, provide a clinical benefit that was not measured in this study. For instance, it may reduce other operative complications, other nosocomial infections, or length of stay in the ICU or hospital. All of these would be potentially clinically relevant but have not been systematically studied and could not be evaluated in this study.


  1. Vincent JL, Bihari DJ, Suter PM, et al. The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. JAMA. 1995;274:639-644.

  2. Blumberg HM, Jarvis WR, Soucie JM, et al. Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study. Clin Infect Dis. 2001;33:177-186.

  3. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348:1546-1554.


October 2005 (Volume 33, Number 10)

Clinical and Economic Consequences of Ventilator-Associated Pneumonia: A Systematic Review

Safdar N, Dezfulian C, Collard HR, Saint S
Crit Care Med. 2005;33:2184-2193

Hospital-acquired pneumonia occurs in 0.5% to 5% of all hospitalized patients, and it is much more frequent among mechanically ventilated patients, occurring with the frequency of 15% to 25% in this important subgroup. That makes VAP the most common nosocomial infection in critically ill patients.[1] VAP is generally associated with prolonged mechanical ventilation, greater hospital length of stay, and higher mortality. Patients with VAP have crude mortality rates of 30% to 70% that include approximately 15% to 50% of directly attributable mortality related to the VAP episode.[2]

The authors sought to determine the specific incidence of VAP and mechanically ventilated patients in the attributable mortality of VAP. They undertook this project by conducting a systematic review of clinical studies of VAP incidence and mortality since 1990. They found that between 10% and 20% of patients who undergo mechanical ventilation for more than 40 hours will develop VAP, and these patients are twice as likely to die compared with patients without VAP. VAP patients have an average 6 days longer length of stay in the ICU and incur approximately $10,000 more of hospital costs.

The results of this study confirm previous observations about the prevalence of this condition and the attributable adverse consequences. Because this condition is so common and associated with both adverse outcomes for patients and additional cost for the healthcare system, the implementation of evidence-based strategies for reducing incidence is critical. There are evidence-based guidelines for the prevention of VAP.[3,4,5,6] These invariably include the universally effective strategies (handwashing and raising the head of the bed to at least 30 degrees above horizontal) and provide guidelines for other strategies such as oral care, rotating antibiotic formularies, various forms of stress ulcer prophylaxis, digestive tract decontamination, aspiration of subglottic secretions, and kinetic beds.[7] The specific application of the strategies depends on the patient population in which they are used. For instance, sucralfate may result in a lower incidence of VAP compared with H2 blockers in selected ventilated patients who are at low risk for experiencing gastrointestinal bleeding. The most important strategy is to recognize the frequency of this condition and to develop institutional strategies that prevent its occurrence.


  1. Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med. 2002;165:867-903.

  2. Heyland DK, Cook DJ, Griffith L, Keenan SP, Brun-Buisson C. The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient. Am J Respir Crit Care Med. 1999;159(4 Pt 1):1249-1256.

  3. American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171:388-416.

  4. Dodek P, Keenan S, Cook D, et al. Evidence-based clinical practice guideline for the prevention of ventilator-associated pneumonia. Ann Intern Med. 2004;141:305-313.

  5. Bergogne-Berezin E. Treatment and prevention of nosocomial pneumonia. Chest. 1995;108(2 suppl):26S-34S.

  6. Collard HR, Saint S, Matthay MA. Prevention of ventilator-associated pneumonia: an evidence-based systematic review. Ann Intern Med. 2003;138:494-501.

  7. Fagon JY, Chastre J, Wolff M, et al. Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia. A randomized trial. Ann Intern Med. 2000;132:621-630.


Annals of Internal Medicine
April 2005 (Volume 142, Number 7)

Meta-analysis: Low-Dose Dopamine Increases Urine Output But Does Not Prevent Renal Dysfunction or Death

Friedrich JO, Adhikari N, Herridge MS, Beyene J
Ann Intern Med. 2005;142:510-524

Intravenous infusion of dopamine has long been advocated as a strategy to improve renal perfusion.[1] This is based on the concept that the dopaminergic receptors in the renal vasculature may be influenced by exogenous dopamine infusion to increase renal blood flow or glomerular filtration. The use of dopamine has been discouraged recently based on the fact that there are no well-conducted trials showing that it improves clinical outcomes.[1]

The authors of this study sought to determine whether existing clinical data confirm or refute a benefit attributable to dopamine infusion in critically ill patients. They conducted a systematic review of published literature comparing low-dose dopamine with either placebo or no therapy in patients with or at risk for ARF. In this body of literature, there were 61 trials of 3359 patients. The results show no effect of low-dose dopamine on mortality, need for renal replacement therapy, or adverse events. Low-dose dopamine did increase urine output by 24% with small decreases in serum creatinine and small increases in creatinine clearance. However, these changes were only evident on day 1 of therapy.

The authors concluded that low-dose dopamine has transient physiologic benefits for the kidney but is without clinical benefit. The use of dopamine to improve renal function has been popular since its initial description in 1963 for patients with chronic congestive heart failure.[2] Studies since that time in patients with or at risk for ARF have failed to find any major clinical benefit.[3,4] However, the use of intravenous low-dose dopamine continued to be popular. This resulted in a large multicenter randomized trial in Australia and New Zealand.[5] This study again found no clinical benefit to low-dose dopamine therapy in patients at risk for ARF or with early ARF. Despite these apparently conclusive results, the use of dopamine has continued to the present day.[6]

The results of this comprehensive systematic review confirm that low-dose dopamine offers no significant clinical benefit for patients at risk for developing ARF. Intravenous infusion of low-dose dopamine does appear to increase urine output modestly for the first 24 hours of therapy, but any changes in serum creatinine or measured creatinine clearance were clinically insignificant. Furthermore, any apparent physiologic benefit did not translate into a clinical benefit. Although there was no difference in adverse events, it is likely that intravenous infusion of dopamine does in fact result in a small increased risk for adverse events, such as tachyarrhythmias. These results, in combination with prior well-conducted randomized controlled trials, should close the door on the prophylactic use of intravenous low-dose dopamine to prevent or manage incipient ARF.


  1. Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004;32:858-873.

  2. Goldberg LI, Mcdonald RH Jr, Zimmerman AM. Sodium diuresis produced by dopamine in patients with congestive heart failure. N Engl J Med. 1963;269:1060-1064.

  3. Corwin HL, Lisbon A. Renal dose dopamine: long on conjecture, short on fact. Crit Care Med. 2000;28:1657-1658.

  4. Galley HF. Renal-dose dopamine: will the message now get through? Lancet. 2000;356:2112-2113.

  5. Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J. Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Lancet. 2000;356:2139-2143.

  6. McHugh GJ. Current usage of dopamine in New Zealand intensive care units. Anaesth Intensive Care. 2001;29:623-626.


Annals of Internal Medicine
November 2005 (Volume 143, Number 10)

Trends in the Incidence of Venous Thromboembolism During Pregnancy or Postpartum: A 30-Year Population-Based Study

Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ
Ann Intern Med. 2005;143:697-706

Deep vein thrombosis (DVT) and venous thromboembolism (VTE) are among the most common complications for hospitalized patients. Published guidelines have espoused the use of effective prophylaxis,[1] although studies have shown that prescription of prophylaxis is woefully inadequate.[2,3] The use of prophylaxis and pregnancy is even more complicated, as contraindications exist for oral warfarin, and intravenous and subcutaneous administration of heparin or heparinoids have potential side effects and require medical skills.

In order to best target prophylaxis to prevent VTE, the authors sought to determine the risk for these events during pregnancy and in the postpartum period. They examined an inception cohort from Olmsted County Minnesota, where prior population-based epidemiology studies have been conducted. Information was gathered on peripartum VTE between 1966 and 1995 from this database. The authors found that pregnant and postpartum women were more than 4 times more likely to develop VTE compared with their nonpregnant counterparts. The annual incidence of VTE was 5 times higher among postpartum women than among pregnant women, and the incidence of DVT was 3 times higher than that of pulmonary embolism.

This well conducted longitudinal epidemiology study confirms the heightened risk for DVT and VTE in pregnant women. However, even more important, the results show that the risk for VTE is 5 times higher in the postpartum period than during pregnancy itself. These data are very useful in targeting prophylaxis for this condition, where attention must be paid to the postpartum period. This is most true for patients who become pregnant with a prior episode of DVT or VTE or those at high risk for these conditions.


  1. Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 suppl):338S-400S.

  2. Hirsch DR, Ingenito EP, Goldhaber SZ. Prevalence of deep venous thrombosis among patients in medical intensive care. JAMA. 1995;274:335-337.

  3. Keane MG, Ingenito EP, Goldhaber SZ. Utilization of venous thromboembolism prophylaxis in the medical intensive care unit. Chest. 1994;106:13-14.


Critical Care
November 2005 (Volume 9, Number 6)

Early Goal-Directed Therapy After Major Surgery Reduces Complications and Duration of Hospital Stay. A Randomised, Controlled Trial

Pearse R, Dawson D, Fawcett J, Rhodes A, Grounds RM, Bennett ED
Crit Care. 2005;9:R687-693

Specific directed forms of hemodynamic management have been shown to reduce complications and improve survival for patients undergoing surgical procedures. Specifically, preoperative or perioperative hemodynamic management improves outcomes after major general surgery.[1,2,3] For patients with septic shock, early goal-directed hemodynamic therapy has also been shown to improve survival.[4] It is presumed that it is both the timing of the intervention and the type of intervention employed that make a difference. The authors of this study sought to evaluate the effect of postoperative goal-directed therapy on complications and clinical outcomes in patients undergoing general surgery.

High-risk general surgical patients were randomized to goal-directed therapy or conventional management. The "goal" of goal-directed therapy was to attain an oxygen delivery index of 600 mL/min/m2 by use of colloid infusion to increase central venous pressure and dopexamine to increase cardiac output. Some 122 patients undergoing vascular, general, or urologic surgery were randomized and completed the protocol. There is greater intravenous colloid infusion in dopexamine use in goal-directed therapy patients. This patient group experienced fewer complications (44% vs 60%, P = .003), and the median duration of hospital stay was shorter (11 days vs 14 days, P = .001). There was no difference in mortality (11% vs 15%, P = .59).

The authors have conducted one of the first studies to utilize postoperative goal-directed therapy in high-risk surgical patients. Their findings of a reduction in consultations and a shorter length of hospital stay are clinically relevant and have implications for both patients and healthcare systems. However, because this study was conducted in a very limited group of surgical patients and because it was conducted out of a single center, it should be replicated by other investigators to confirm the validity of the findings. Certainly, if these benefits can be attained by such therapy, they could be broadly utilized throughout the developed world. In comparison with prior studies,[1,2,3] this study finds a benefit with a specific hemodynamic management protocol even in the postoperative period. This is in contrast to the other major studies that have found a benefit only in the preoperative or perioperative periods. It will also be important to understand why this therapy works and whether the protocol must be implemented together or whether there are specific component of the protocol that are more important than others. Regardless, the study shows promise as a way to improve outcomes for the growing number patients who undergo high-risk surgical procedures each year.


  1. Boyd O, Grounds RM, Bennett ED, et al. A randomized clinical trial of the effect of deliberate peri-operative increase of oxygen delivery on mortality in high-risk surgical patients. JAMA. 1993;270:2699-2707.

  2. Shoemaker WC, Appel PL, Kram HB, Waxman K, Lee TS. Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients. Chest. 1988;94:1176-1186.

  3. Wilson J, Woods I, Fawcett GJ, et al. Reducing the risk of major elective surgery: a randomized controlled trial of preoperative optimization of oxygen delivery. BMJ. 1999;318:1099-1103.

  4. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-1377.



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