Ca Den Uil

The Heterogeneity of the Microcirculation in Critical Illness

Microcirculation, a complex and specialized facet of organ architecture, has characteristics that vary according to the function of the tissue it supplies. Bedside technology that can directly observe microcirculation in patients, such as orthogonal polarization spectral imaging and sidestream dark field imaging, has opened the way to investigating this network and its components, especially in critical illness and surgery. These investigations have underscored the central role of microcirculation in perioperative disease states. They have also highlighted variations in the nature of microcirculation, both among organ systems and within specific organs. Supported by experimental studies, current investigations are better defining the nature of microcirculatory alterations in critical illness and how these alterations respond to therapy. This review focuses on studies conducted to date on the microcirculatory beds of critically ill patients. The functional anatomy of microcirculation networks and the role of these networks in the pathogenesis of critical illness are discussed. The morphology of microvascular beds that have been visualized during surgery and intensive care at the bedside are also described, including those of the brain, sublingual region, skin, intestine, and eyes.

Perioperative Blood Glucose Monitoring and Control in Major Vascular Surgery Patients

Diabetes mellitus (DM) is an independent predictor for morbidity and mortality in the general population, which is even more apparent in patients with concomitant cardiovascular risk factors. As the prevalence of DM is increasing, with an ageing general population, it is expected that the number of diabetic patients requiring surgical interventions will increase. Perioperative hyperglycaemia, without known DM, has been identified as a predictor for morbidity and mortality in patients undergoing surgery. Moreover, early studies showed that intensive blood-glucose-lowering therapy reduced both morbidity and mortality among patients admitted to the postoperative intensive care unit (ICU). However, later studies have doubted the benefit of intensive glucose control in medical-surgical ICU patients. This article aims to comprehensively review the evidence on the use of perioperative intensive glucose control, and to provide recommendations for current clinical practice. A systematic review was performed of the literature on perioperative intensive glucose control. Based on this literature review, we observed that intensive glucose control in the perioperative period has no clear benefit on short-term mortality. Intensive glucose control may even have a net harmful effect in selected patients. In addition, concerns on the external validity of some studies are important barriers for widespread recommendation of intensive glucose control in the perioperative setting. We propose that guidelines recommending intensive glucose control should be re-evaluated. In addition, moderate tight glucose control should currently be regarded as the safest and most efficient approach to patients undergoing major vascular surgery.

ACE insertion/deletion polymorphism in sepsis and acute respiratory distress syndrome

With great interest, we read the article by Villar et al., who investigated the angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism in relationship to sepsis and acute respiratory syndrome (ARDS) in over 300 Spanish patients. The authors did not find an association between this polymorphism and susceptibility, and outcome in either severe sepsis or ARDS [1]. In our opinion, the authors’ explanation for this lack of association is not sufficiently discussed and we hope to open the discussion on this topic by raising several issues. First, the authors correctly noted that ACE is an important enzyme involved in cardiovascular homeostasis [2]. We are disappointed that the authors investigated only one (non-functional) polymorphism in the ACE-gene. Instead of investigating one polymorphism, we would have preferred analysis of common variation in the complete ACE-gene, which would have been easy and feasible in such a relatively small population. This would have significantly strengthened any associations between ACE-genotypes and sepsis. In addition, it is good to realize that the ACE I/D polymorphism is only responsible for less than 20% variation of plasma ACE levels. It is hard to believe that such a single polymorphism accounts for a significant causal effect on endpoints such as sepsis and ARDS, which are probably syndromes that are highly influenced by microbial characteristics and polygenetic factors. Second, the authors reported a statistical power of 76–85% using a sample size of 212 septic and 120 ARDS patients. An adequate study size and statistical power are necessary to exclude false negative or positive association studies. An important review article in this field recently addressed that a number of 2,000 patients with sepsis would be required to detect a mortality relative risk of 1.5 from any polymorphism [3]. Third, the authors did not fully explain why the ACE I/ D polymorphism could be important in sepsis, since individuals who have the DD-genotype usually have higher ACE levels relative to controls, whereas in septic ARDS patients markedly decreased plasma ACE levels have been observed [4, 5]. In this respect, it would have been nice if the authors would have correlated their findings to plasma ACE levels. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Microcirculation and multi-organ failure in patients with sepsis

With great interest, we read the article by Trzeciak et al. who made a commendable effort to investigate whether an improvement in SOFA score over the first 24 h in patients with sepsis was associated with an increase in sublingual microcirculatory perfusion. The authors demonstrated a significant increase in median microvascular flow index (MFI) for SOFA improvers versus non-improvers (?0.23 vs. -0.05, respectively) [1]. Although we appreciate these interesting findings, we would like to raise several comments. First, the authors quantified microcirculatory flow using a semi-quantitative method presented previously [2]. Using this method produces a MFI for small (i.e. capillaries, 0–20 lm), medium (20–50 lm) and large (50–100 lm) sized microvessels. Analyses of vessels larger than capillaries (i.e. mainly venules) is of limited interest, but experts in the field of microcirculation research recently advised that venular perfusion should also be reported as a quality control index [3]. However, the authors only mentioned a single MFI per time point. Did they produce an averaged MFI for all micro-vessels in a certain video-microscopic image? Since capillaries are the vessels that are impaired most in sepsis [2, 4], calculation of an averaged MFI for all microvessels would definitely restrain any changes in observed microvascular perfusion. Second, individual patient data for MFI in the electronic supplementary material show a clear difference in change of MFI between both subgroups. However, we would like to learn whether median MFI at visit 2 was statistically different between SOFA improvers versus non-improvers (in contrast with the almost equal values of MFI at baseline). Although we can imagine that a trend in perfusion over time might be more important than single values, a single-value threshold, indicating whether microcirculation is either preserved or impaired at a certain moment, would have considerable practical advantages over the continuous monitoring of trends. Finally, the authors demonstrated that there is an association between early increases in microcirculatory perfusion and multi-organ failure. However, it will be very hard to visualize the modest changes, as presented by the authors, in individual patients at the bedside and the clinical value of a change in MFI of 0.23 points may be very difficult to interpret. In order to implement a future microcirculation-directedapproach to our patients with sepsis, additional research is necessary.