Risk indicators for acute kidney injury in cardiogenic shock.

PURPOSE: In critical illness, the relation between the macrocirculation, microcirculation and organ dysfunction, such as acute kidney injury (AKI), is complex. This study aimed at identifying predictors for AKI in patients with cardiogenic shock. MATERIALS AND METHODS: Thirty-nine adult cardiogenic shock patients, with an admission creatinine <200 µmol l-1, and whose microcirculation was measured within 48 h were enrolled. Patient data were analyzed if AKI stage ≥1 developed according to the Kidney Disease/Improving Outcomes classification within 48 h after admission. Variables with a p < .05 in the univariate analysis were considered for analysis with logistic regression. RESULTS: Twenty-four patients (61.5%) developed AKI within 48 h. The group that developed AKI had higher central venous pressures (CVP), lower diastolic arterial blood pressures and mean perfusion pressures, higher maximum ventilator pressures as well as positive end expiratory pressures and were treated with higher dosages of dobutamine. There was no difference of the microcirculation. In the multivariate logistic regression analysis, CVP was the only independent predictor for AKI (OR 1.241; 95% CI 1.030-1.495; p = .023). CONCLUSIONS: In this population of patients with cardiogenic shock, CVP was associated with the development of AKI.

Prevention of acute kidney injury and protection of renal function in the intensive care unit: update 2017 : Expert opinion of the Working Group on Prevention, AKI section, European Society of Intensive Care Medicine.

BACKGROUND: Acute kidney injury (AKI) in the intensive care unit is associated with significant mortality and morbidity. OBJECTIVES: To determine and update previous recommendations for the prevention of AKI, specifically the role of fluids, diuretics, inotropes, vasopressors/vasodilators, hormonal and nutritional interventions, sedatives, statins, remote ischaemic preconditioning and care bundles. METHOD: A systematic search of the literature was performed for studies published between 1966 and March 2017 using these potential protective strategies in adult patients at risk of AKI. The following clinical conditions were considered: major surgery, critical illness, sepsis, shock, exposure to potentially nephrotoxic drugs and radiocontrast. Clinical endpoints included incidence or grade of AKI, the need for renal replacement therapy and mortality. Studies were graded according to the international GRADE system. RESULTS: We formulated 12 recommendations, 13 suggestions and seven best practice statements. The few strong recommendations with high-level evidence are mostly against the intervention in question (starches, low-dose dopamine, statins in cardiac surgery). Strong recommendations with lower-level evidence include controlled fluid resuscitation with crystalloids, avoiding fluid overload, titration of norepinephrine to a target MAP of 65-70 mmHg (unless chronic hypertension) and not using diuretics or levosimendan for kidney protection solely. CONCLUSION: The results of recent randomised controlled trials have allowed the formulation of new recommendations and/or increase the strength of previous recommendations. On the other hand, in many domains the available evidence remains insufficient, resulting from the limited quality of the clinical trials and the poor reporting of kidney outcomes.

Procalcitonin to guide taking blood cultures in the intensive care unit; a cluster-randomized controlled trial.

OBJECTIVES: We aimed to study the safety and efficacy of procalcitonin in guiding blood cultures taking in critically ill patients with suspected infection. METHODS: We performed a cluster-randomized, multi-centre, single-blinded, cross-over trial. Patients suspected of infection in whom taking blood for culture was indicated were included. The participating intensive care units were stratified and randomized by treatment regimen into a control group and a procalcitonin-guided group. All patients included in this trial followed the regimen that was allocated to the intensive care unit for that period. In both groups, blood was drawn at the same moment for a procalcitonin measurement and blood cultures. In the procalcitonin-guided group, blood cultures were sent to the department of medical microbiology when the procalcitonin was >0.25 ng/mL. The main outcome was safety, expressed as mortality at day 28 and day 90. RESULTS: The control group included 288 patients and the procalcitonin-guided group included 276 patients. The 28- and 90-day mortality rates in the procalcitonin-guided group were 29% (80/276) and 38% (105/276), respectively. The mortality rates in the control group were 32% (92/288) at day 28 and 40% (115/288) at day 90. The intention-to-treat analysis showed hazard ratios of 0.85 (95% CI 0.62-1.17) and 0.89 (95% CI 0.67-1.17) for 28-day and 90-day mortality, respectively. The results were deemed non-inferior because the upper limit of the 95% CI was below the margin of 1.20. CONCLUSION: Applying procalcitonin to guide blood cultures in critically ill patients with suspected infection seems to be safe, but the benefits may be limited. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ID NCT01847079. Registered on 24 April 2013, retrospectively registered.

The diagnostic accuracy of procalcitonin for bacteraemia: a systematic review and meta-analysis.

The diagnostic use of procalcitonin for bacterial infections remains a matter of debate. Most studies have used ambiguous outcome measures such as sepsis instead of infection. We performed a systematic review and meta-analysis to investigate the diagnostic accuracy of procalcitonin for bacteraemia, a proven bloodstream infection. We searched all major databases from inception to June 2014 for original, English language, research articles that studied the diagnostic accuracy between procalcitonin and positive blood cultures in adult patients. We calculated the area under the summary receiver-operating characteristic (SROC) curves and pooled sensitivities and specificities. To minimize potential heterogeneity we performed subgroup analyses. In total, 58 of 1567 eligible studies were included in the meta-analysis and provided a total of 16,514 patients, of whom 3420 suffered from bacteraemia. In the overall analysis the area under the SROC curve was 0.79. The optimal and most widely used procalcitonin cut-off value was 0.5 ng/mL with a corresponding sensitivity of 76% and specificity of 69%. In subgroup analyses the lowest area under the SROC curve was found in immunocompromised/neutropenic patients (0.71), the highest area under the SROC curve was found in intensive-care patients (0.88), sensitivities ranging from 66 to 89% and specificities from 55 78%. In spite of study heterogeneity, procalcitonin had a fair diagnostic accuracy for bacteraemia in adult patients suspected of infection or sepsis. In particular low procalcitonin levels can be used to rule out the presence of bacteraemia. Further research is needed on the safety and efficacy of procalcitonin as a single diagnostic tool to avoid taking blood cultures.

Intravascular versus surface cooling speed and stability after cardiopulmonary resuscitation.

BACKGROUND AND OBJECTIVE: Mild therapeutic hypothermia (MTH) is used to limit neurological injury and improve survival after cardiac arrest (CA) and cardiopulmonary resuscitation, but the optimal mode of cooling is controversial. We therefore compared the effectiveness of MTH using invasive intravascular or non-invasive surface cooling with temperature feedback control. METHODS: This retrospective study in post-CA patients studied the effects of intravascular cooling (CoolGard, Zoll, n=97), applied on the intensive care unit (ICU) in one university hospital compared with those of surface cooling (Medi-Therm, Gaymar, n=76) applied in another university hospital. RESULTS: Time to reach target temperature and cooling speeds did not differ between groups. During the maintenance phase, mean core temperature was 33.1°C (range 32.7-33.7°C) versus 32.5°C (range 31.7-33.4°C) at targets of 33.0 and 32.5°C in intravascularly versus surface cooled patients, respectively. The variation coefficient for temperature during maintenance was higher in the surface than the intravascular cooling group (mean 0.85% vs 0.35%, p<0.0001). ICU survival was 60% and 50% in the intravascularly and surface cooled groups, respectively (NS). Lower age (OR 0.95; 95% CI 0.93 to 0.98; p<0.0001), ventricular fibrillation/ventricular tachycardia as presenting rhythm (OR 7.6; 95% CI 1.8 to 8.9; p<0.0001) and lower mean temperature during the maintenance phase (OR 0.52; 95% CI 0.25 to 1.08; p=0.081) might be independent determinants of ICU survival, while cooling technique and temperature variability did not contribute. CONCLUSIONS: In post-CA patients, intravascular cooling systems result in equal cooling speed, but less variation in temperature during the maintenance phase, as surface cooling. This may not affect the outcome.

Metabolic response to the stress of critical illness.

The metabolic response to stress is part of the adaptive response to survive critical illness. Several mechanisms are well preserved during evolution, including the stimulation of the sympathetic nervous system, the release of pituitary hormones, a peripheral resistance to the effects of these and other anabolic factors, triggered to increase the provision of energy substrates to the vital tissues. The pathways of energy production are altered and alternative substrates are used as a result of the loss of control of energy substrate utilization by their availability. The clinical consequences of the metabolic response to stress include sequential changes in energy expenditure, stress hyperglycaemia, changes in body composition, and psychological and behavioural problems. The loss of muscle proteins and function is a major long-term consequence of stress metabolism. Specific therapeutic interventions, including hormone supplementation, enhanced protein intake, and early mobilization, are investigated. This review aims to summarize the pathophysiological mechanisms, the clinical consequences, and therapeutic implications of the metabolic response to stress.

Systematic review of uncalibrated arterial pressure waveform analysis to determine cardiac output and stroke volume variation.

UNLABELLED: The FloTrac/Vigileo™, introduced in 2005, uses arterial pressure waveform analysis to calculate cardiac output (CO) and stroke volume variation (SVV) without external calibration. The aim of this systematic review is to evaluate the performance of the system. Sixty-five full manuscripts on validation of CO measurements in humans, published in English, were retrieved; these included 2234 patients and 44,592 observations. RESULTS: have been analysed according to underlying patient conditions, that is, general critical illness and surgery as normodynamic conditions, cardiac and (post)cardiac surgery as hypodynamic conditions, and liver surgery and sepsis as hyperdynamic conditions, and subsequently released software versions. Eight studies compared SVV with other dynamic indices. CO, bias, precision, %error, correlation, and concordance differed among underlying conditions, subsequent software versions, and their interactions, suggesting increasing accuracy and precision, particularly in hypo- and normodynamic conditions. The bias and the trending capacity remain dependent on (changes in) vascular tone with most recent software. The SVV only moderately agreed with other dynamic indices, although it was helpful in predicting fluid responsiveness in 85% of studies addressing this. Since its introduction, the performance of uncalibrated FloTrac/Vigileo™ has improved particularly in hypo- and normodynamic conditions. A %error at or below 30% with most recent software allows sufficiently accurate and precise CO measurements and trending for routine clinical use in normo- and hypodynamic conditions, in the absence of large changes in vascular tone. The SVV may usefully supplement these measurements.

A review of the hemodynamic effects of external leg and lower body compression.

BACKGROUND: External leg and lower body compression (ELC) has been used for decades in the prevention of deep vein thrombosis and the treatment of leg ischemia. Because of systemic effects, the methods have regained interest in anesthesia, surgery and critical care. This review intends to summarize hemodynamic effects and their mechanisms. METHODS: Compilation of relevant literature published in English as full paper and retrieved from Medline. RESULTS: By compressing veins, venous stasis is diminished and venous return and arterial blood flow are increased. ELC has been suggested to improve systemic hemodynamics, in different clinical settings, such as postural hypotension, anesthesia, surgery, shock, cardiopulmonary resuscitation and mechanical ventilation. However, the hemodynamic alterations depend upon the magnitude, extent, cycle, duration and thus the modality of ELC, when applied in a static or intermittent fashion (by pneumatic inflation), respectively. CONCLUSION: ELC may help future research and optimizing treatment of hemodynamically unstable, surgical or critically ill patients, independent of plasma volume expansion.

Basic concepts of fluid responsiveness.

Predicting fluid responsiveness, the response of stroke volume to fluid loading, is a relatively novel concept that aims to optimise circulation, and as such organ perfusion, while avoiding futile and potentially deleterious fluid administrations in critically ill patients. Dynamic parameters have shown to be superior in predicting the response to fluid loading compared with static cardiac filling pressures. However, in routine clinical practice the conditions necessary for dynamic parameters to predict fluid responsiveness are frequently not met. Passive leg raising as a means to alter biventricular preload in combination with subsequent measurement of the change in stroke volume can provide a fast and accurate way to guide fluid management in a broad population of critically ill patients.

Cardiopulmonary interactions during mechanical ventilation in critically ill patients.

Cardiopulmonary interactions induced by mechanical ventilation are complex and only partly understood. Applied tidal volumes and/or airway pressures largely mediate changes in right ventricular preload and afterload. Effects on left ventricular function are mostly secondary to changes in right ventricular loading conditions. It is imperative to dissect the several causes of haemodynamic compromise during mechanical ventilation as undiagnosed ventricular dysfunction may contribute to morbidity and mortality.

Use of synthetic colloids in sepsis: a critical review on efficacy, safety and patient benefits.

In this narrative review, the studies and analyses are discussed that pertain to benefits and detriments of synthetic colloids versus natural colloids or crystalloids used for fluid resuscitation in sepsis and septic shock. The relative amount of fluid infusions used to reach clinical or hemodynamic end-points are reviewed, as well as potential toxicity of starch solutions on the kidney. Hence, it cannot be excluded that adverse effects partly offset beneficial hemodynamic effects that are similar to that of natural colloids, so that in most analyses a mortality benefit of synthetic colloid fluid resuscitation in sepsis and septic shock cannot be demonstrated.

Clinical implications of heart-lung interactions.

As opposed to spontaneous respiration wherein small cyclic changes in transpulmonary, negative pressure coincide with lung volume changes, positive pressure (mechanical) ventilation results in a simultaneous rise in transpulmonary pressure and lung volumes. The changes may affect biventricular cardiac loading and function in dissimilar ways, depending on baseline cardiopulmonary function. This review is intended to update current knowledge on the pathophysiology of these heart-lung interactions in helping to explain the common circulatory alterations occurring during airway pressure changes and to better understand mechanisms of disease and modes of action of treatments, during spontaneous and mechanical ventilation.

Assessing effects of PEEP and global expiratory lung volume on regional electrical impedance tomography.

OBJECTIVE: This study was performed to assess the value of electrical impedance tomography (EIT) as an indicator of tidal (V(T)) and end expiratory lung volume (EELV). METHODS: EIT measurements were performed in seven healthy piglets during constant tidal volume ventilation at incremental and decremental positive end-expiratory pressure (PEEP) levels. Tidal impedance changes were calibrated to volume using V(T) calculated from flow at the airway opening. Simultaneously, calibrated respiratory inductive plethysmography was used to measure EELV changes, and used as a reference standard. RESULTS: EIT systematically underestimated both V(T) and EELV changes when EELV deviated from the level at which it was calibrated. Calculated over the entire pressure-volume curve, EIT systematically underestimated V(T) by 28 ml, with a precision from -16 to 72 ml. EELV was systemically underestimated by 406 ml, with a precision of -38 to 849 ml. Nonlinear recruitment in the ventral regions of the lungs was the main cause of this underestimation. CONCLUSIONS: Tidal and end-expiratory changes in pulmonary impedance reflect corresponding changes in lung volume, but the increasing underestimation with increasing lung volume should be taken into account in the analysis of EIT data.

Acute necrotizing pancreatitis following inadvertent extensive splenic artery embolisation for trauma.

We present a case of splenic artery embolisation (SAE) after traumatic splenic injury that was complicated by acute necrotizing pancreatitis, caused by inadvertently extensive embolisation of the splenic artery. Although SAE is increasingly used for splenic preservation in trauma, there is insufficient knowledge on its efficacy and pitfalls. This report aims to draw attention to a rare but potentially serious complication of SAE.

Angiopoietin-2, permeability oedema, occurrence and severity of ALI/ARDS in septic and non-septic critically ill patients.

BACKGROUND: Angiopoietin-2 and vascular endothelial growth factor (VEGF) may impair vascular barrier function while angiopoietin-1 may protect it. It was hypothesised that circulating angiopoietin-2 is associated with pulmonary permeability oedema and severity of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) during septic or non-septic critical illness. METHODS: Plasma levels of angiopoietin-1 and angiopoietin-2 were measured in mechanically ventilated patients (24 with sepsis, 88 without sepsis), together with the pulmonary leak index (PLI) for 67-gallium-labelled transferrin and extravascular lung water (EVLW) by transpulmonary thermal-dye dilution as measures of pulmonary permeability and oedema, respectively. ALI/ARDS was characterised by consensus criteria and the lung injury score (LIS). Plasma VEGF and von Willebrand factor (VWF) levels were assayed. RESULTS: Angiopoietin-2, VWF, PLI, EVLW and LIS were higher in patients with sepsis than in those without sepsis and higher in patients with ALI/ARDS (n = 10/12 in sepsis, n = 19/8 in non-sepsis) than in those without. VEGF was also higher in patients with sepsis than in those without. Patients with high PLI, regardless of EVLW, had higher angiopoietin-2 levels than patients with normal PLI and EVLW. Angiopoietin-2 correlated with the PLI, LIS and VWF levels (minimum r = 0.34, p<0.001) but not with EVLW. Angiopoietin-2 and VWF were predictive for ARDS in receiver operating characteristic curves (minimum area under the curve = 0.69, p = 0.006). Angiopoietin-1 and VEGF did not relate to the permeability oedema of ALI/ARDS. CONCLUSION: Circulating angiopoietin-2 is associated with pulmonary permeability oedema, occurrence and severity of ALI/ARDS in patients with and without sepsis. The correlation of angiopoietin-2 with VWF suggests activated endothelium as a common source.

The relationship between arterial PO2 and mixed venous PO2 in response to changes in positive end-expiratory pressure in ventilated patients.

The response of arterial PO(2) (P(a)O(2)) to airway pressure has been used as a measure of recruitment in mechanically ventilated patients. We hypothesised that mixed venous PO(2) (P(mv)O(2)) directly affects P(a)O(2). Sixteen patients with acute lung injury (ALI, lung injury score > or = 1) on volume-controlled mechanical ventilation (F(I)O(2) 0.40) were studied. Positive end-expiratory pressure (PEEP) was increased and decreased. Incremental PEEP increased median values of P(a)O(2), diminished venous admixture (Q(va)/Q(t)) and cardiac index, but maintained arterial PCO(2) and tissue O(2) uptake. These changes were reversed during decremental PEEP. However P(a)O(2) did not increase in 37% of PEEP steps and changes in P(a)O(2) correlated to those in P(mv)O(2) (r(s) = 0.45, p < 0.001). Changes in P(mv)O(2) contributed to changes in Q(va)/Q(t) in determining changes in P(a)O(2) (p < 0.05). P(mv)O(2) may be an independent determinant of P(a)O(2) during mechanical ventilation for ALI, so that dosing PEEP to recruit the lung should not be guided by arterial blood oxygenation alone. Arterial hypoxaemia with increasing PEEP may improve by reducing PEEP (or increasing tissue O(2) delivery), when the fall in P(mv)O(2) is greater than about 0.133 kPa.

Management of invasive pulmonary aspergillosis in non-neutropenic critically ill patients.

During recent years, a rising incidence of invasive pulmonary aspergillosis (IPA) in non-neutropenic critically ill patients has been reported. Critically ill patients are prone to develop disturbances in immunoregulation during their stay in the ICU, which render them more vulnerable for fungal infections. Risk factors such as chronic obstructive pulmonary disease (COPD), prolonged use of steroids, advanced liver disease, chronic renal replacement therapy, near-drowning and diabetes mellitus have been described. Diagnosis of IPA may be difficult and obtaining histo- or cytopathological demonstration of the fungus in order to meet the gold standard for IPA is not always feasible in these patients. Laboratory markers used as a non-invasive diagnostic tool, such as the galactomannan antigen test (GM), 1,3-beta-glucan, and Aspergillus PCR, show varying results. Antifungal therapy might be considered in patients with persistent pulmonary infection who exhibit risk factors together with positive cultures or sequentially positive GM and Aspergillus PCR in serum, in whom voriconazole is the drug of choice. The benefit of combination antifungal therapy lacks sufficient evidence so far, but this treatment might be considered in patients with breakthrough infections or refractory disease.

An update on acute kidney injury after cardiac surgery.

Renal dysfunction following cardiac surgery is well recognised and mainly is of ischaemic origin. The spectrum varies from subclinical injuryto established renal failure requiring renal replacement therapy. Depending on definitions, acute kidney injury (AKI) may occur in up to 30% of post cardiac surgery patients. A new grading system for renal dysfunction, based on three levels of plasma creatinine and urine output, as well as the use of biomarkers may help the early identification of patients at risk and thereby hopefully improve outcome. Despite therapeutic advances, the morbidity and mortality associated with AKI have not changed markedly in the last decade.

The role of procalcitonin in a decision tree for prediction of bloodstream infection in febrile patients.

Bloodstream infection (BSI) in febrile patients is associated with high mortality. Clinical and laboratory variables, such as procalcitonin (PCT), may predict BSI and help decision-making concerning empirical treatment. This study compared two models for prediction of BSI, and evaluated the role of PCT vs. clinical variables, collected daily in 300 consecutive febrile inpatients, for 48 h after onset of fever. Multiple logistic regression (MLR) and classification and regression tree (CART) models were compared for discriminatory power and diagnostic performance. BSI was present in 17% of cases. MLR identified the presence of intravascular devices, nadir albumin and thrombocyte counts, and peak temperature, respiratory rate and leukocyte counts, but not PCT, as independent predictors of BSI. In contrast, a peak PCT level of >2.45 ng/mL was the principal discriminator in the decision tree based on CART. The latter was more accurate (94%) than the model based on MLR (72%; p <0.01). Hence, the presence of BSI in febrile patients is predicted more accurately and by different variables, e.g., PCT, in CART analysis, as compared with MLR models. This underlines the value of PCT plus CART analysis in the diagnosis of a febrile patient.