Martin Westphal

In the absence of evidence, therapies are often based on intuition, belief, common sense or gut feeling. Over the years, some treatment strategies may become dogmas that are eventually considered as state-of-the-art and not questioned any longer. This might be a reason why there are many examples of “strange” treatments in medical history that have been applied in the absence of evidence and later abandoned for good reasons. In this article, five dogmas relevant to critical care medicine are discussed and reviewed in the light of the available evidence. Dogma #1 relates to the treatment of oliguria with fluids, diuretics, and vasopressors. In this context, it should be considered that oliguria is a symptom rather than a disease. Thus, once hypovolaemia can be excluded as the underlying reason, there is no justification for giving fluids, which may do more harm than good in euvolaemic or hypervolaemic patients. Similarly, there is no solid evidence for forcing diuresis by administering vasopressors and loop diuretics. Dogma #2 addresses the treatment of crush syndrome patients with aggressive fluid therapy using NaCl 0.9%. In fact, this treatment may aggravate renal injury by iatrogenic metabolic acidosis and subsequent renal hypoperfusion. Dogma #3 concerns the administration of NaCl 0.9% to patients undergoing kidney transplantation. Since these patients are usually characterised by hyperkalaemia, the potassium-free solution NaCl 0.9%, containing exclusively 154 mmol/l of sodium and chloride ions each, is often considered as the fluid of choice. However, large volumes of chloride-rich solutions cause hyperchloraemic acidosis in a dose-dependent manner and induce a potassium shift to the extracellular space, thereby increasing serum potassium levels. Thus, balanced electrolyte solutions are to be preferred in this setting. Dogma #4 relates to the fact that enteral nutrition is often withheld for patients with high residual gastric volume due to the theoretical risk of gastro-oesophageal reflux, potentially resulting in aspiration pneumonitis. Despite controversial discussions, there is no clinical data supporting that residual gastric volume should be generally measured, especially not in patients without a gastro-intestinal surgery and/or motility disorders. Clinical evidence rather suggests that abandoning residual gastric volume monitoring does not increase the incidence of pneumonia, but may benefit patients by facilitating adequate enteral feeding. Finally, dogma #5 is about sedating all mechanically ventilated patients because “fighting” against the respirator may cause insufficient ventilation. This concern needs to be balanced against the unwanted consequences of sedation, such as prolonged mechanical ventilation and intensive care unit length of stay as well as increased risk of delirium. Modern concepts based on adequate analgesia and moderate to no sedation appear to be more suitable. In conclusion, dogmas are still common in clinical practice. Since science rather than fiction should govern our actions in intensive care medicine, it is important to remain critical and challenge long established concepts, especially when the underlying evidence is weak or non-existing.

Red blood cell (RBC) transfusion might be life-saving in settings with acute blood loss, especially uncontrolled haemorrhagic shock. However, there appears to be a catch-22 situation reflected by the facts that preoperative anaemia represents an independent risk factor for postoperative morbidity and mortality, and that RBC transfusion might also contribute to adverse clinical outcomes. This dilemma is further complicated by the difficulty to define the “best” transfusion trigger and strategy. Since one size does obviously not fit all, a personalised approach is merited. Attempts should thus be made to critically reflect on the pros and cons of RBC transfusion in each individual patient. Patient blood management concepts including preoperative, intraoperative and postoperative optimisation strategies involving the intensive care unit are warranted and are likely to provide benefits for the patients and the healthcare system. In this context, it is important to consider that “simply” increasing the haemoglobin content, and in proportion oxygen delivery, may not necessarily contribute to a better outcome but potentially the contrary in the long term. The difficulty lies in identification of the patients who might eventually profit from RBC transfusion and to determine in whom a transfusion might be withheld without inducing harm. More robust clinical data providing long-term outcome data are needed to better understand in which patients RBC transfusion might be life-saving vs life-limiting.

Although mortality after cardiac surgery has significantly decreased in the last decade, patients still experience clinically relevant postoperative complications. Among others, atrial fibrillation (AF) is a common consequence of cardiac surgery, which is associated with prolonged hospitalization and increased mortality. We retrospectively analyzed data from patients who underwent coronary artery bypass grafting, valve surgery or a combination of both at the University Hospital Muenster between April 2014 and July 2015. We evaluated the incidence of new onset and intermittent/permanent AF (patients with pre- and postoperative AF). Furthermore, we investigated the impact of postoperative AF on clinical outcomes and evaluated potential risk factors. In total, 999 patients were included in the analysis. New onset AF occurred in 24.9% of the patients and the incidence of intermittent/permanent AF was 59.5%. Both types of postoperative AF were associated with prolonged ICU length of stay (median increase approx. 2 days) and duration of mechanical ventilation (median increase 1 h). Additionally, new onset AF patients had a higher rate of dialysis and hospital mortality and more positive fluid balance on the day of surgery and postoperative days 1 and 2. In a multiple logistic regression model, advanced age (odds ratio (OR) = 1.448 per decade increase, p < 0.0001), a combination of CABG and valve surgery (OR = 1.711, p = 0.047), higher C-reactive protein (OR = 1.06 per unit increase, p < 0.0001) and creatinine plasma concentration (OR = 1.287 per unit increase, p = 0.032) significantly predicted new onset AF. Higher Horowitz index values were associated with a reduced risk (OR = 0.996 per unit increase, p = 0.012). In a separate model, higher plasma creatinine concentration (OR = 2.125 per unit increase, p = 0.022) was a significant risk factor for intermittent/permanent AF whereas higher plasma phosphate concentration (OR = 0.522 per unit increase, p = 0.003) indicated reduced occurrence of this arrhythmia. New onset and intermittent/permanent AF are associated with adverse clinical outcomes of elective cardiac surgery patients. Different risk factors implicated in postoperative AF suggest different mechanisms might be involved in its pathogenesis. Customized clinical management protocols seem to be warranted for a higher success rate of prevention and treatment of postoperative AF.

Life-threatening diseases of critically ill patients are known to derange microcirculation. Automatic analysis of microcirculation would provide a bedside diagnostic tool for microcirculatory disorders and allow immediate therapeutic decisions based upon microcirculation analysis. After induction of general anaesthesia and instrumentation for haemodynamic monitoring, haemorrhagic shock was induced in ten female sheep by stepwise blood withdrawal of 3 × 10 mL per kilogram body weight. Before and after the induction of haemorrhagic shock, haemodynamic variables, samples for blood gas analysis, and videos of conjunctival microcirculation were obtained by incident dark field illumination microscopy. Microcirculatory videos were analysed (1) manually with AVA software version 3.2 by an experienced user and (2) automatically by AVA software version 4.2 for total vessel density (TVD), perfused vessel density (PVD) and proportion of perfused vessels (PPV). Correlation between the two analysis methods was examined by intraclass correlation coefficient and Bland-Altman analysis. The induction of haemorrhagic shock decreased the mean arterial pressure (from 87 ± 11 to 40 ± 7 mmHg; p < 0.001); stroke volume index (from 38 ± 14 to 20 ± 5 ml·m−2; p = 0.001) and cardiac index (from 2.9 ± 0.9 to 1.8 ± 0.5 L·min−1·m−2; p < 0.001) and increased the heart rate (from 72 ± 9 to 87 ± 11 bpm; p < 0.001) and lactate concentration (from 0.9 ± 0.3 to 2.0 ± 0.6 mmol·L−1; p = 0.001). Manual analysis showed no change in TVD (17.8 ± 4.2 to 17.8 ± 3.8 mm*mm−2; p = 0.993), whereas PVD (from 15.6 ± 4.6 to 11.5 ± 6.5 mm*mm−2; p = 0.041) and PPV (from 85.9 ± 11.8 to 62.7 ± 29.6%; p = 0.017) decreased significantly. Automatic analysis was not able to identify these changes. Correlation analysis showed a poor correlation between the analysis methods and a wide spread of values in Bland-Altman analysis. As characteristic changes in microcirculation during ovine haemorrhagic shock were not detected by automatic analysis and correlation between automatic and manual analyses (current gold standard) was poor, the use of the investigated software for automatic analysis of microcirculation cannot be recommended in its current version at least in the investigated model. Further improvements in automatic vessel detection are needed before its routine use.

Great white sharks are responsible for about 10 cases of death annually worldwide, as compared with millions of deaths caused by sepsis. However, the basic principles of avoiding shark attacks and fighting sepsis seem to be similar: avoidance, attention, and speed, if necessary. The present review discusses the current status of the systemic inflammatory response syndrome (SIRS) criteria, which are actually content for discussion because of their low specificity. Current data suggest that one in eight patients with severe sepsis does not fulfill the SIRS criteria and is consequently missed, and therefore the calls for new definitions of sepsis are getting louder. Furthermore, the need for early treatment of sepsis and fast admission to an intensive care unit (ICU) with experienced stuff is reviewed as well as the early and appropriate initiation of therapy, namely antibiotic and volume therapy. A key feature is the analysis of the studies from the so-called "Sepsis Trilogy" (ProCESS, ARISE, and ProMiSe studies), with a focus on the status of early goal-directed therapy (EGDT). The authors of the "Sepsis Trilogy" concluded that there is no benefit regarding survival in septic patients by using EGDT as compared with standard therapy. However, the low mortality of the control groups within the "Sepsis Trilogy" studies as compared with the Rivers et al. study from 2001 leads to the conclusion that there has been an improvement in the therapy of septic patients, most probably due to the early initiation of therapy as a kind of "standard" in sepsis therapy. Finally, the phenomenon of a "large trial disease" is discussed, exemplary in a trial which investigated the maintenance of the "right" mean arterial pressure in sepsis patients. Even if the result of a large randomized trial might be that there is no difference between two study groups, the real exercise is to identify the patient collectives who might benefit or experience harm due to an intervention. In summary, as compared with swimming in dangerous waters, high attention is needed in handling septic patients. Once an attack has occurred, speed is of utmost importance (i.e., initiation of therapy and admission to the ICU) because it appears logical that time is critical in septic patients This may have resulted in the implementation of early (goal-directed) treatment as a "standard" in the treatment of sepsis with significant improvement in survival.

Introduction: The present study was designed to determine the effects of continuously infused norepinephrine (NE) plus (1) terlipressin (TP) or (2) arginine vasopressin (AVP) or (3) placebo on sublingual microcirculation in septic shock patients. The primary study end point was a difference of ≥ 20% in the microvascular flow index of small vessels among groups. Methods: The design of the study was a prospective, randomized, double-blind clinical trial. NE was titrated to maintain mean arterial pressure (MAP) between 65 and 75 mmHg after establishment of normovolemia in 60 septic shock patients. Thereafter patients (n = 20 per group) were randomized to receive continuous infusions of either TP (1 μg/kg/hour), AVP (0.04 U/minute) or placebo (isotonic saline). In all groups, open-label NE was adjusted to maintain MAP within threshold values if needed. The sublingual microcirculatory blood flow of small vessels was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and norepinephrine requirements, were obtained at baseline and 6 hours after randomization. Results: TP and AVP decreased NE requirements at the end of the 6-hour study period. The data are medians (25th and 75th interquartile ranges (IQRs)): 0.57 μg/kg/minute (0.29 to 1.04) vs. 0.16 μg/kg/minute (0.03 to 0.37) for TP and 0.40 μg/kg/minute (0.20 to 1.05) vs. 0.23 μg/kg/minute (0.03 to 0.77) for AVP, with statistical significance of P < 0.05 vs. baseline and vs. placebo. There were no differences in sublingual microcirculatory variables, systemic hemodynamics, oxygen transport and acid-base homeostasis among the three study groups during the entire observation period. The proportions of perfused vessels increased in relation to baseline within all study groups, and there were no significant differences between groups. The specific data were as follows (median (IQR)): 9.7% (2.6 to 19.8) for TP, 8.9% (0.0 to 17.8) for AVP, and 6.9% (3.5 to 10.1) for placebo (P < 0.05 vs. baseline for each comparison), as well as perfused vessel density 18.6% (8.6 to 36.9) for TP, 20.2% (-3.0 to 37.2) for AVP, and 11.4% (-3.0 to 19.4) for placebo (P < 0.05 vs. baseline for each comparison). Conclusions: The present study suggests that to achieve a MAP of 65 to 75 mmHg in septic patients treated with NE, the addition of continuously infused low-dose TP or AVP does not affect sublingual microcirculatory blood flow. In addition, our results suggest that microcirculatory flow abnormalities are mainly related to other factors (for example, volume status, timing, hemodynamics and progression of the disease) rather than to the vasopressor per se. Trial registration: ClinicalTrial.gov NCT00995839

Zur Deckung des Basisflüssigkeitsbedarfs von intensivmedizinisch behandelten Patienten sollte man balancierte, kristalloide Lösungen infundieren. Eine Verwendung von Humanalbumin oder synthetischen Kolloiden zur Reduktion des kumulativen Flüssigkeitsbedarfs ist aufgrund der aktuellen Datenlage nicht indiziert. Die zielgerichtete Volumentherapie sollte unter Verwendung eines erweiterten Monitorings mit sensitiven und spezifischen Markern der Volumenreagibilität (Schlagvolumenmessung, Pulskonturanalyse, transpulmonale Thermodilution oder Echokardiografie) gesteuert werden. Eine lebensbedrohliche Hypovolämie kann mit isoonkotischen Kolloiden besser behandelt werden als mit Kristalloiden. Es ist derzeit unklar, ob durch den Einsatz von Kolloiden zur Therapie der akuten Hypovolämie das Outcome kritisch kranker Patienten beeinflusst wird. Des Weiteren ist nicht geklärt, ob man bei dieser Indikation Humanalbumin oder moderne synthetische Kolloide (z. B. 6 % HES 130/0,4 oder 130/0,42) verwenden sollte. Die potenziellen positiven Effekte einer kontinuierlichen Substitution von Humanalbumin bei hypalbuminämen Patienten sollten separat vom Volumeneffekt in klinischen Studien evaluiert werden. Bezüglich der Effekte moderner Kolloide auf die Nierenfunktion sind weitere prospektive, klinische Studien erforderlich, die die Auswirkungen auf valide Marker der Nierenfunktion und -schädigung bei indikationsgerechtem Gebrauch untersuchen (Infobox 3).

Introduction: The purpose of the present study was to investigate microcirculatory blood flow in patients with septic shock treated with levosimendan as compared to an active comparator drug (i.e. dobutamine). The primary end point was a difference of ≥ 20% in the microvascular flow index of small vessels (MFIs) among groups. Methods: The study was designed as a prospective, randomized, double-blind clinical trial and performed in a multidisciplinary intensive care unit. After achieving normovolemia and a mean arterial pressure of at least 65 mmHg, 40 septic shock patients were randomized to receive either levosimendan 0.2 μg·kg^-1·min^-1 (n = 20) or an active comparator (dobutamine 5 μg·kg^-1·min^-1; control; n = 20) for 24 hours. Sublingual microcirculatory blood flow of small and medium vessels was assessed by sidestream dark-field imaging. Microcirculatory variables and data from right heart catheterization were obtained at baseline and 24 hours after randomization. Baseline and demographic data were compared by means of Mann-Whitney rank sum test or chi-square test, as appropriate. Microvascular and hemodynamic variables were analyzed using the Mann-Whitney rank sum test. Results: Microcirculatory flow indices of small and medium vessels increased over time and were significantly higher in the levosimendan group as compared to the control group (24 hrs: MFIm 3.0 (3.0; 3.0) vs. 2.9 (2.8; 3.0); P = .02; MFIs 2.9 (2.9; 3.0) vs. 2.7 (2.3; 2.8); P < .001). The relative increase of perfused vessel density vs. baseline was significantly higher in the levosimendan group than in the control group (dMFIm 10 (3; 23)% vs. 0 (-1; 9)%; P = .007; dMFIs 47 (26; 83)% vs. 10 (-3; 27); P < .001). In addition, the heterogeneity index decreased only in the levosimendan group (dHI -93 (-100; -84)% vs. 0 (-78; 57)%; P < .001). There was no statistically significant correlation between systemic and microcirculatory flow variables within each group (each P > .05). Conclusions: Compared to a standard dose of 5 μg·kg^-1·min^-1 of dobutamine, levosimendan at 0.2 μg·kg^-1·min^-1 improved sublingual microcirculatory blood flow in patients with septic shock, as reflected by changes in microcirculatory flow indices of small and medium vessels. Trial registration: NCT00800306.