Critical Care - Latest Articles

Target blood pressure in sepsis: between a rock and a hard place

Thiago Corrêa — 2013-05-17T00:00:00Z

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Sex and Severe Sepsis

Bertrand Guidet — 2013-05-15T00:00:00Z

Epidemiological studies document that males are more prone than females to develop severe sepsis and this is confirmed by Sakr and colleagues in the previous issue of Critical Care. However, the impact of gender on prognosis of severe sepsis is a matter of debate. Sakr and colleagues report a higher mortality in septic females than in males. This puzzling result might be explained by confounding factors such as age, nosocomial infections, follow-up period, and case mix. The impact of sexual hormones in older females is less relevant. Treatments aimed at modifying sexual hormone profile are promising but need to be tested in future trials.

Commentary

folke sjoberg — 2013-05-15T00:00:00Z

The importance of adequate sleep for good health and immune system function is well documented as is reduced sleep quality experienced by ICU patients. In this issue of Critical Care, Elliot and co-workers present [1], a well done, largest of its kind, single center study on sleep patterns in critically ill patients. They base their study on the "gold standard", the polysomnography technique (PSG), which is resource demanding to perform and often difficult to evaluate. The results are especially interesting as the authors did not only do PSG in a large sample but also, in contrast to others excluded patients with prior sleep problems. They also recorded the patient's subjective sleep experiences in the ICU and thereafter in the ward (validated questionnaires) with simultaneous data collection of factors known to affect sleep in the ICU, mainly treatment interventions, light and sound disturbances. Interestingly, but not surprising, sleep was both quantitatively and qualitatively poor. Furthermore there seemed to be little or no improvement over time when compared to earlier studies. This study stresses the magnitude of the sleep problem despite interventions such as earplugs and/or eyeshades. Sound disturbance was found to be the most significant but improvable factor. The study highlights the challenge of and the importance of evaluating sleep in the critical care setting and the present need for alternative methods measure it. All that in conjunction can be used to solve an important problem for this patient group.

Dopexamine: immunomodulatory, hemodynamic, or both?

Steven Hollenberg — 2013-05-13T00:00:00Z

Dopexamine is a dopamine analog that has been used for hemodynamic optimization in a number of clinical settings. This animal investigation showed anti-inflammatory effects of dopexamine in a rat endotoxin model without effects on global or regional flow, but it is not time to dispense with hemodynamics altogether just yet. Rather, an integrative approach to the effects of catecholamines, considering both inflammatory and hemodynamic effects, including those on the microcirculation, can help clinicians best understand how to employ them in clinical practice.

Parenteral diclofenac infusion significantly decreases brain tissue oxygen tension in patients with poor-grade aneurysmal subarachnoid hemorrhage

Alois Schiefecker — 2013-05-12T00:00:00Z

IntroductionDiclofenac, a nonsteroidal anti-inflammatory drug, is commonly used as antipyretic therapy in intensive care. The purpose of this study was to investigate the effects of parenteral diclofenac infusion on brain homeostasis including brain tissue oxygen tension (PbtO2) and brain metabolism after aneurismal subarachnoid hemorrhage (aSAH). Methods: We conducted a prospective, observational study with retrospective analysis of 21 consecutive aSAH patients with multimodal neuromonitoring. Cerebral perfusion pressure (CPP), mean arterial pressure (MAP), intracranial pressure (ICP), body temperature and PbtO2 were analyzed after parenteral diclofenac infusion administered over 34 minutes (20-45 IQR). Data are given as mean+/-standard error of mean and median with interquartile range (IQR) as appropriate. Time-series data were analyzed using a general linear model extended by generalized estimation equations (GEE). Results: One-hundred-twenty-three interventions were analyzed. Body temperature decreased from 38.3+/-0.05degreesC by 0.8+/-0.06degreesC (P<0.001). A 10% decrease in MAP and CPP (P<0.001) necessitated an increase of vasopressors in 26% (N=32), colloids in 33% (N=41) and cristalloids in 5% (N=7) of interventions. PbtO2 decreased by 13% from a baseline value of 28.1+/-2.2mmHg, resulting in brain tissue hypoxia (PbtO2<20mmHg) in 38% (N=8) of patients and 35% (N=43) of interventions. PbtO2 < 30mmHg before intervention was associated with brain tissue hypoxia after parenteral diclofenac infusion (Likelihood ratio 40; AUC 93%; 95% CI 87-99%; P<0.001). Cerebral metabolism showed no significant changes after parenteral diclofenac infusion. Conclusions: Parenteral diclofenac infusion after aSAH effectively reduces body temperature, but may lead to CPP decrease and brain tissue hypoxia, which were both associated with poor outcome after aSAH.

Continuous on-line glucose measurement by microdialysis in a central vein. A pilot study

Christina Blixt — 2013-05-11T00:00:00Z

IntroductionTight glucose control in the ICU has been proven difficult with an increased risk for hypoglycaemic episodes. Also the variability of glucose may have an impact on morbidity. An accurate and feasible on-line/continuous measurement is therefore desired. In this study a central vein catheter with a microdialysis membrane in combination with an on-line analyzer for continuous monitoring of circulating glucose and lactate by the central route was tested. Methods: 10 patients scheduled for major upper abdominal surgery were included in this observational prospective study at a university hospital. The patients received an extra central venous catheter with a microdialysis membrane placed in the right jugular vein. Continuous microdialysis measurement proceeded for 20 hours and on-line values were recorded every minute. As reference arterial plasma glucose and blood lactate samples were collected every hour. Results: Mean microdialysis-glucose during measurements was 9.8+/-2.4mmol/l. No statistical difference in the readings was seen using single calibration compared to eighth hour calibration (p=0.09; t-test). There was a close agreement between the continuous reading and the reference plasma glucose values with an absolute difference of 0.6+0.8mmol, or 6.8+9.3% and measurements showed high correlation to plasma readings (r=0.92). The limit of agreement was 23.0% (1.94 mmol/l) compared to arterial plasma values with a line of equality close to zero. However, in a Clarke-Error Grid 93.3% of the values are in the A-area , and the remaining part in the B-area.Mean microdialysis-lactate was 1.3+/-1.1mmol/l. The measurements showed high correlation to the blood readings (r=0.93). Conclusion: Continuous on-line microdialysis glucose measurement in a central vein is a potential useful technique for continuous glucose monitoring in critically ill patients, but more improvements and testing is needed.

Antithrombin attenuates myocardial dysfunction and reverses systemic fluid accumulation following burn and smoke inhalation injury: a randomized, controlled, experimental study

Sebastian Rehberg — 2013-05-11T00:00:00Z

IntroductionWe hypothesized that maintaining physiological plasma levels of antithrombin attenuates myocardial dysfunction and inflammation as well as vascular leakage associated with burn and smoke inhalation injury. Therefore, the present prospective, randomized experiment was conducted using an established ovine model. Methods: Following 40% of total body surface area, 3rd degree flame burn and 4x12 breaths of cold cotton smoke, chronically instrumented sheep were randomly assigned to receive an intravenous infusion of 6 IUkg-1h-1 recombinant human antithrombin (rhAT) or normal saline (control group; n=6 each). In addition, six sheep were designated as sham animals (not injured, continuous infusion of vehicle). During the 48h study period the animals were awake, mechanically ventilated and fluid resuscitated according to standard formulas Results: Compared to the sham group, myocardial contractility was severely impaired in control animals, as suggested by lower stroke volume and left ventricular stroke work indexes. As a compensatory mechanism heart rate increased, thereby increasing myocardial oxygen consumption. In parallel, myocardial inflammation was induced via nitric oxide production, neutrophil accumulation (myeloperoxidase activity) and activation of the p38-mitogen-activated protein kinase pathway resulting in cytokine release (tumor necrosis factor-alpha, interleukin-6) in control vs. sham animals. rhAT-treatment significantly attenuated these inflammatory changes leading to a myocardial contractility and myocardial oxygen consumption comparable to sham animals. In control animals, systemic fluid accumulation progressively increased over time resulting in a cumulative positive fluid balance of about 4000ml at the end of the study period. Contrary, in rhAT-treated animals there was only an initial fluid accumulation until 24h that was reversed back to the level of sham animals during the second day. Conclusions: Based on these findings, the supplementation of rhAT may represent a valuable therapeutic approach for cardiovascular dysfunction and inflammation after burn and smoke inhalation injury.

Blockade of the negative co-stimulatory molecules PD-1 and CTLA-4 improves survival in primary and secondary fungal sepsis

Katherine Chang — 2013-05-11T00:00:00Z

IntroductionFungal sepsis is an increasingly common problem in intensive care unit patients. Mortality from fungal sepsis remains high despite antimicrobial therapy that is highly active against most fungal pathogens, a finding consistent with defective host immunity that is present in many patients with disseminated fungemia. One recently recognized immunologic defect that occurs in patients with sepsis is T cell "exhaustion" due to increased expression of programmed cell death -1 (PD-1). This study tested the ability of anti-PD-1 and anti-programmed cell death ligand -1 (anti-PD-L1) antagonistic antibodies to improve survival and reverse sepsis-induced immunosuppression in two mouse models of fungal sepsis. Methods: Fungal sepsis was induced in mice using two different models of infection, i.e., primary fungal sepsis and secondary fungal sepsis occurring after sub-lethal cecal ligation and puncture (CLP). Anti-PD-1 and anti-PD-L1 were administered 24-48 hrs after fungal infection and effects on survival, interferon gamma production, MHC II expression, and delayed-type hypersensitivity response were examined. Results: Anti-PD-1 and anti-PD-L1 antibodies were highly effective at improving survival in primary and secondary fungal sepsis. Both antibodies reversed sepsis-induced suppression of interferon gamma and increased expression of MHC II on antigen presenting cells. Blockade of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a second negative co-stimulatory molecule that is upregulated in sepsis and acts like PD-1 to suppress T cell function, also improved survival in fungal sepsis. Conclusions: Immuno-adjuvant therapy with anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies reverse sepsis-induced immunosuppression and improve survival in fungal sepsis. The present results are consistent with previous studies showing that blockade of PD-1 and CTLA-4 improves survival in bacterial sepsis. Thus, immuno-adjuvant therapy represents a novel approach to sepsis and may have broad applicability in the disorder. Given the relative safety of anti-PD-1 antibody in cancer clinical trials to date, therapy with anti-PD-1 in patients with life-threatening sepsis who have demonstrable immunosuppression should be strongly considered.

Algorithm-based management of bleeding in patients with extracorporeal membrane oxygenation.

David Faraoni — 2013-05-08T00:00:00Z

Coagulation management is a challenge during extracorporeal membrane oxygenation (ECMO) due to the complex hemostatic and inflammatory responses associated with the underlying conditions that include infection, sepsis, surgery, and/or traumatic injury. This letter considers three comments to a recent study published in Critical Care.

Does space make waste? The influence of ICU bed capacity on admission decisions.

Esteban Mery — 2013-05-08T00:00:00Z

Expanded abstractCitationStelfox HT, Hemmelgarn BR, Bagshaw SM, Gao S, Doig CJ, Nijssen-Jordan C, Manns B: Intensive care unit bed availability and outcomes for hospitalized patients with sudden clinical deterioration. Arch Intern Med 2012, 172:467-474. Background: Intensive care unit (ICU) beds are a scarce resource, and admissions may require prioritization when demand exceeds supply. However, there are few empiric data on whether the availability of ICU beds influences triage and processes of care for hospitalized patients who develop sudden clinical deterioration. Methods: ObjectiveThe objective was to evaluate the effect of ICU bed availability on the processes and outcomes of care for hospitalized patients with sudden clinical deterioration on a hospital ward.DesignWe conducted a retrospective cohort study.SettingThe study was conducted in three hospitals in Calgary, Alberta, Canada, with 2,040 beds and a catchment population of 1.5 million individuals.SubjectsHospitalized adults (n = 3,494) with a sudden clinical deterioration triggering medical emergency team (MET) activation between 1 January 2007 and 31 December 2009 participated.AnalysisThis study compared treatments and outcomes among sudden clinical deterioration patients according to the number of ICU beds available (zero, one, two, or more than two) at the time of the MET activation. The outcomes of interest were ICU admission rates (within 2 hours of MET activation), changes in the goals of care (resuscitative, medical, and comfort), and hospital mortality. All analyses were adjusted for hospital, physician, and patient factors. Results: The cohort consisted of 3,494 patients. Reduced ICU bed availability was associated with a decreased likelihood of ICU admission within 2 hours of MET activation (P = 0.03) and with an increased likelihood of change in patient goals of care (P <0.01). Patients with sudden clinical deterioration when zero ICU beds were available were 33.0% (95% confidence interval (CI), −5.1% to57.3%) less likely to be admitted to the ICU and were 89.6% (95% CI, 24.9% to 188.0%) more likely to have their goals of care changed compared with when more than two ICU beds were available. However, hospital mortality did not vary significantly by ICU bed availability (P = 0.82). Conclusions: For hospitalized patients with sudden clinical deterioration, ICU bed scarcity decreases the probability of ICU admission and increases the probability of initiating comfort measures on the ward but does not influence hospital mortality.