Critical Care - Latest articles

Procalcitonin in liver transplantation: are high levels due to donors or recipients?

2008-07-04

IntroductionTo date, a specific marker to evaluate and predict the liver transplanted patient clinical course or complication is not available in clinical practice. Increased procalcitonin (PCT) levels have been found in infectious inflammation; poor organ perfusion and high PCT level in cardiac donor appeared to predict early graft failure. We evaluated PCT as a predictor of early graft dysfunction and postoperative complications. Methods: PCT serum concentrations were measured in samples collected before organ retrieval from 67 consecutive brain-dead donors and in corresponding recipients from day 0, before liver transplantation, up to day 7 after liver transplantation. The following parameters were recorded, in donors: amount of vasopressive drug doses, cardiac arrest history 24 hours before retrieval, number of days in intensive care unit (ICU), age of donor, infection in donor and in recipients: cold and warm ischemia time, veno-venous bypass, transfusion amount during orthotopic liver transplantation (OLT), occurrence of postoperative complication, or hepatic dysfunction. Results: In the donor, the preoperative level of PCT was associated with cardiac arrest and high doses of catecholamines before organ retrieval. In the recipient, elevated PCT levels were observed early after OLT, with a peak at Day 1 or 2 after OLT, then a decrease until day 7. A postoperative peak of PCT levels was associated neither with preoperative PCT levels in the donor or the recipients nor with hepatic post-OLT dysfunction or other post operative complications, but with two donor's parameters: infection and cardiac arrest. Conclusions: PCT level in the donor and early PCT peak in recipient are not predictive of post OLT hepatic dysfunction or other complications. Cardiac arrest and infection in the donor, but not PCT level in the donor, are associated with high post OLT procalcitonin levels in the recipient.

Normal adrenocortical function on initial testing in the intensive care unit: not a long-term warranty

Pierre-Edouard Bollaert — 2008-07-02

There has been a lot of debate about the concept of relative adrenocortical insufficiency (often defined as a reduced response to corticotropin) as a pathophysiological explanation of steroid effects in septic shock. Less is known about the prevalence of absolute adrenocortical insufficiency based on more usual definitions (low baseline and corticotropin stimulated cortisol). The study by Wu et al provides convincing evidence that critically ill patients could evolve from a normal adrenal status towards very low cortisol levels within a few days.

Opioid-induced constipation in intensive care patients: relief in sight?

Daniel Chappell, Markus Rehm and Peter Conzen — 2008-07-01

Constipation is the most common gastrointestinal complication associated with opioid therapy in chronic pain patients, and also frequently occurs in sedated intensive care unit patients. Conventional therapy may not provide sufficient relief from constipation, which can be severe enough to limit opioid use or the dose. In a recent study on terminally ill patients suffering from laxative-resistant opioid-induced constipation, Thomas and colleagues demonstrated subcutaneous methylnaltrexone to rapidly induce defecation. This appealing result might also have favourable prospects for intensive care patients, as their outcome is often codetermined by recovery of bowel functioning.

Surviving sepsis: a guide to the guidelines

Jean-Louis Vincent and John C Marshall — 2008-06-30

The revised Surviving Sepsis Campaign (SSC) guidelines for the management of severe sepsis and septic shock have recently been published. These guidelines represent the end product of an intense process and provide a template approach to the early resuscitation and support of patients with sepsis, based on a synthesis of evidence that has been shown to improve the outcome of the septic patient. The SSC guidelines arose from a recognition that care of the septic patient was suboptimal for at least three reasons. First, the entity of sepsis was frequently not diagnosed in a timely fashion, allowing the process to evolve into a life-threatening syndrome of major physiologic organ system dysfunction. Secondly, even when sepsis was recognized, the urgency of treatment was underappreciated – and so haemodynamic resuscitation was tentative, and the administration of effective antibiotic therapy was often delayed. Finally, treatment was often suboptimal, and failed to take advantage of emerging insights into optimal approaches to patient management. The revised guidelines are far from perfect, but they represent the best available synthesis of contemporary knowledge in this area and as such should be promoted.

Heparin-induced thrombocytopenia during renal replacement therapy in the intensive care unit

Andrew Davenport — 2008-06-30

Whereas some 30% to 50% of patients admitted to the intensive care unit develop thrombocytopenia during their stay, the incidence of heparin-induced thrombocytopenia (HIT) remains low, at around 0.3% to 0.5%. Lasocki and colleagues prospectively tested patients with premature clotting of the hemofiltration circuit for HIT, and reported a 25% incidence of HIT, particularly if the circuit clotted within 6 hours. By switching the anticoagulant from heparin to danaparoid, the hemofiltration circuit survival and urea clearances improved. HIT should therefore be clinically suspected if extracorporeal circuits clot repeatedly.

Anti-PF4/heparin antibodies associated with repeated hemofiltration-filter clotting: a retrospective study

2008-06-25

IntroductionHeparin-induced thrombocytopenia is an immune mediated adverse drug reaction that is associated with a procoagulant state and both arterial and venous thrombosis. After observing two cases of repeated hemofiltration-filter clotting associated with high anti-PF4/Heparin antibody concentrations, we systematically measured anti-PF4/Heparin antibody concentration in all cases of unexpected and repeated hemofiltration-filter clotting during continuous veno-venous hemofiltration (CVVH). The aim of this study was to identify factors associated with positive anti-PF4/Heparin antibody in the case of repeated hemofiltration filter clotting. Methods: We reviewed the charts of all patients who had an anti-PF4/Heparin antibody assay performed for repeated hemofiltration filter clotting between November 2004 and May 2006 in our surgical intensive care unit. We used an enzyme-linked immunoabsorbent assay (ELISA, HPIA, Diagnostica Stago, Paris, France) with an optical density (OD)>1 IU considered positive. Results: During the study period, anti-PF4/Heparin antibody assay was performed in 28 out of 87 patients receiving CVVH. Seven patients were positive for anti-PF4/Heparin antibodies (OD 2.00[1.36-2.22] IU) and 21 were antibody-negative (OD 0.20[0.10-0.32] IU). Baseline characteristics, platelet counts, aPTT ratios were not different between the two groups. CVVH duration was significantly decreased in antibody-positive patients (5.0[2.5-7.5] vs 12.0[7.5-15 24.0] hours, p=0.007) as was CVVH efficiency (urea reduction ratio: 17[10-37] vs 44[30-52]%, p=0.04) on heparin infusion. Anti-PF4/Heparin antibody concentration was inversely correlated with CVVH duration. The ROC curve showed that a 6-hour cut-off was the best CVVH session duration to predict a positive antibody test (sensitivity: 71%, specificity: 85%, area under the curve: 0.83). CVVH duration (32[22-37] hours, p<0.05) and urea reduction (55[36-68]%, p<0.03) were restored by danaparoid sodium infusion. Conclusions: Repeated hemofiltration-filter clotting in less than 6 hours was often associated with the presence of anti-PF4/Heparin antibodies, regardless of the platelet count. In antibody-positive patients, replacement of heparin by danaparoid sodium allowed restoration of CVVH duration and efficiency.

Clinical review: Influenza pandemic – physicians and their obligations

Devanand Anantham, Wendy McHugh, Stephen O'Neill and Lachlan Forrow — 2008-06-24

An influenza pandemic threatens to be the most lethal public health crisis to confront the world. Physicians will have critical roles in diagnosis, containment and treatment of influenza, and their commitment to treat despite increased personal risks is essential for a successful public health response. The obligations of the medical profession stem from the unique skills of its practitioners, who are able to provide more effective aid than the general public in a medical emergency. The free choice of profession and the societal contract from which doctors derive substantial benefits affirm this commitment. In hospitals, the duty will fall upon specialties that are most qualified to deal with an influenza pandemic, such as critical care, pulmonology, anesthesiology and emergency medicine. It is unrealistic to expect that this obligation to treat should be burdened with unlimited risks. Instead, risks should be minimized and justified against the effectiveness of interventions. Institutional and public cooperation in logistics, remuneration and psychological/legal support may help remove the barriers to the ability to treat. By stepping forward in duty during such a pandemic, physicians will be able to reaffirm the ethical center of the profession and lead the rest of the healthcare team in overcoming the medical crisis.

Probiotics in the intensive care unit: why controversies and confusion abound

Lee E Morrow and Marin H Kollef — 2008-06-24

Probiotics are living microorganisms that, when administered in adequate amounts, confer health benefits on the host. Because probiotics are not marketed as pharmaceuticals, they are commercially available without rigorous scientific documentation of their efficacy for many health-related claims. Results from existing clinical trials are both confusing and controversial. The evidence base is relatively limited, includes studies with varied designs, assesses multiple probiotic preparations across discrepant disease states, and provides conflicting results. Recent advances in the delineation of probiotics' mechanisms of action offer the opportunity to construct a more logical framework within which future trials are designed.

Association of HMGB1 polymorphisms with outcome in patients with systemic inflammatory response syndrome

2008-06-24

IntroductionHigh mobility group box 1 protein (HMGB1) is a pleiotropic cytokine, recently implicated in the pathophysiology of the systemic inflammatory response syndrome and sepsis. Data from experimental sepsis models show that administration of anti-HMGB1 antibodies significantly decreased mortality, even when administration was delayed for 24 hours, providing a window of opportunity for therapeutic intervention if transferred into a clinical setting. Whether genetic variation in the human HMGB1-gene is associated with disease susceptibility is unknown. Methods: We sequenced the HMGB1-gene in 239 prospectively monitored patients, with SIRS admitted to an intensive care unit and measured the corresponding HMGB1 serum concentrations, as controls served blood donors. Outcome parameters according to different HMGB1 genotypes were compared. Results: Homozygosity and heterozygosity for a promoter variant (-1377delA) was associated with a decreased overall 4 year survival (15% vs 44%, HR 1.80 (p=0.01)) and decreased number of SIRS criteria, while carriage of an exon 4 variant (982C>T) was significantly associated with increased number of SIRS criteria, higher SAPSII score, lower PaO2/FiO2 ratio, lower serum HMGB1 levels (p=0.01) and significantly higher probability of early death due to infection (p=0.04). HMGB1 was undetectable in the controls. Conclusions: This is the first report of clinical implications of variation in the human HMGB1 gene. Two polymorphisms were determined as significant risk factors associated with early and late mortality, which may provide insight into the molecular background of SIRS and sepsis, suggesting a possible role for HMGB1 genetics in future prognostic evaluation.

Circulating cytokines and outcome prediction of burned children with concomitant inhalation injury

Pavlos M Myrianthefs and George J Baltopoulos — 2008-06-23

Being able to accurately predict probability of death is important for the intensivist. Serum cytokine levels parallel physiological derangements observed in critically ill patients and are used in commonly applied scoring systems and prediction models. Thus, serum cytokine based prediction models of outcome seem to be reasonable and of great interest. In this issue of Critical Care, Gauglitz and colleagues present their prediction equation for paediatric burn patients with concomitant inhalation injury. They found that IL-10 on admission, or IL-6 and IL-7 five to seven days later, may predict outcome in an excellent way. Increased mortality is observed as serum IL-6 and IL-10 levels increase and serum IL-7 levels decrease. However, the complexity of cytokine kinetics in critically ill patients and the variety of factors capable to affect circulating cytokines even in a subgroup of critically ill patients may affect the valitidy of the results. Also, serum cytokine based prediction models need to be compared to commonly applied prediction models based on clinical parameters. This will enable identification of the most suitable, accurate, cheapest, and easiest to use model to predict outcome.