The predictive value of phase angle on long-term outcome after ICU admission.

INTRODUCTION: The use of severity of illness scoring systems, including the Acute Physiology and Chronic Health Evaluation (APACHE) III score, has made it possible to compare groups of patients and evaluate treatment strategies. Phase angle, derived from bio-impedance analysis, reflects tissue quality and quantity in which cell mass, membrane integrity and hydration state are represented. We hypothesized that phase angle on ICU admission may serve as a proxy for physical frailty and as such can be used as an additional predictor of long-term mortality after ICU admission. METHODS: A single-center prospective observational cohort study with consecutive patients, admitted to the ICU between June 2018 and June 2019. Demographic data, APACHE III, comorbidity, and phase angle in the first 6 h after ICU admission were collected and the ICU, hospital, and 1-year survival were registered. RESULTS: Of all 1023 patients, 115 (11%) died within a year after ICU admission. Nonsurvivors had higher APACHE III scores than survivors [86 (65-119) vs. 55 (46-67), p < 0.001]. Phase angle was significantly higher in survivors than in nonsurvivors [5.4 (4.7-6.4) vs. 4.7 (3.9-6.0), p < 0.001]. Univariate analysis showed an association between mortality and admission type, sepsis, presence of malignancy, APACHE III, and PhA. Multivariate logistic regression analysis using these variables confirmed low PhA to be an independent predictor of 1-year mortality (OR: 1.81; CI: 1.09-2.97; p = 0.02), in addition to presence of malignancy (OR: 2.30; CI: 1.31-4.02; p = 0.004) and APACHE III score (OR: 1.03; CI: 1.02-1.04; p < 0.001). CONCLUSION: In this single center study, low phase angle was independently associated with 1-year all-cause mortality after ICU admission. CLINICALTRIALS: gov number: NCT0444976.

The contemporary pulmonary artery catheter. Part 1: placement and waveform analysis.

Nowadays, the classical pulmonary artery catheter (PAC) has an almost 50-year-old history of its clinical use for hemodynamic monitoring. In recent years, the PAC evolved from a device that enabled intermittent cardiac output measurements in combination with static pressures to a monitoring tool that provides continuous data on cardiac output, oxygen supply and-demand balance, as well as right ventricular (RV) performance. In this review, which consists of two parts, we will introduce the difference between intermittent pulmonary artery thermodilution using cold bolus injections, and the contemporary PAC enabling continuous measurements by using a thermal filament which at random heats up the blood. In this first part, the insertion techniques, interpretation of waveforms of the PAC, the interaction of waveforms with the respiratory cycle and airway pressure as well as pitfalls in waveform analysis are discussed. The second part will cover the measurements of the contemporary PAC including measurement of continuous cardiac output, RV ejection fraction, end-diastolic volume index, and mixed venous oxygen saturation. Limitations of all of these measurements will be highlighted there as well. We conclude that thorough understanding of measurements obtained from the PAC are the first step in successful application of the PAC in daily clinical practice.

The contemporary pulmonary artery catheter. Part 2: measurements, limitations, and clinical applications.

Nowadays, the classical pulmonary artery catheter (PAC) has an almost 50-year-old history of its clinical use for hemodynamic monitoring. In recent years, the PAC evolved from a device that enabled intermittent cardiac output measurements in combination with static pressures to a monitoring tool that provides continuous data on cardiac output, oxygen supply and-demand balance, as well as right ventricular performance. In this review, which consists of two parts, we will introduce the difference between intermittent pulmonary artery thermodilution using bolus injections, and the contemporary PAC enabling continuous measurements by using a thermal filament which heats up the blood. In this second part, we will discuss in detail the measurements of the contemporary PAC, including continuous cardiac output measurement, right ventricular ejection fraction, end-diastolic volume index, and mixed venous oxygen saturation. Limitations of all of these measurements are highlighted as well. We conclude that thorough understanding of measurements obtained from the PAC is the first step in successful application of the PAC in daily clinical practice.

Can sidestream dark field (SDF) imaging identify subtle microvascular changes of the bowel during colorectal surgery?

BACKGROUND: Recognition of a non-viable bowel during colorectal surgery is a challenging task for surgeons. Identifying the turning point in serosal microcirculatory deterioration leading up to a non-viable bowel is crucial. The aim of the present study was to determine whether sidestream darkfield (SDF) imaging can detect subtle changes in serosal microcirculation of the sigmoid after vascular transection during colorectal surgery. METHODS: A prospective observational clinical study was performed at a single medical centre. All eligible participants underwent laparoscopic sigmoid resection and measurements were taken during the extra-abdominal phase. Microcirculation was measured at the transected bowel and 20 cm proximal to this point. Microcirculatory parameters such as Microvascular Flow Index (MFI), proportion of perfused vessels (PPV), perfused vessel density (PVD), total vessel density (TVD) and the Heterogeneity Index were determined. Data are presented as median (interquartile range) or mean ± standard deviation. RESULTS: A total of 60 SDF images were acquired for 10 patients. Perfusion parameters and perfused vessel density were significantly lower at the transected bowel compared with the non-transected measurements [MFI 2.29 (1.96-2.63) vs 2.96 (2.73-3.00), p = 0.007; PPV 74% (55-83) vs 94% (86-97), p = 0.007; and PVD 7.61 ± 2.99 mm/mm2 versus 10.67 ± 1.48 mm/mm2, p = 0.009]. Total vessel density was similar between the measurement locations. CONCLUSIONS: SDF imaging can identify changes of the bowel serosal microcirculation. Significantly lower serosal microcirculatory parameters of the vascular transected bowel was seen compared with the non-transected bowel. The ability of SDF imaging to detect subtle differences holds promise for future research on microvascular cut-off values leading to a non-viable bowel.

Effects of Thoracic Epidural Anaesthesia on the Serosal Microcirculation of the Human Small Intestine.

BACKGROUND: The effect of thoracic epidural analgesia (TEA) on splanchnic blood flow during abdominal surgery remains unclear. The purpose of this study was to examine whether the hemodynamic effects of TEA resulted in microcirculatory alterations to the intestinal serosa, which was visualized using incident dark-field (IDF) videomicroscopy. METHODS: An observational cohort study was performed. In 18 patients, the microcirculation of the intestinal serosa was visualized with IDF. Microcirculatory and hemodynamic measurements were performed prior to (T1) and after administering a bolus of levobupivacaine (T2). If correction of blood pressure was indicated, a third measurement was performed (T3). The following microcirculatory parameters were calculated: microvascular flow index, proportion of perfused vessels, perfused vessel density and total vessel density. Data are presented as median [IQR]. RESULTS: Mean arterial pressure decreased from 73 mmHg (68-83) at T1 to 63 mmHg (±11) at T2 (p = 0.001) with a systolic blood pressure of 114 mmHg (98-128) and 87 (81-97), respectively (p = 0.001). The microcirculatory parameters of the bowel serosa, however, were unaltered. In seven patients, blood pressure was corrected to baseline values from a MAP of 56 mmHg (55-57), while microcirculatory parameters remained constant. CONCLUSION: We examined the effects of TEA on the intestinal serosal microcirculation during abdominal surgery using IDF imaging for the first time in patients. Regardless of a marked decrease in hemodynamics, microcirculatory parameters of the bowel serosa were not significantly affected. TRIAL REGISTRY NUMBER: ClinicalTrials.gov identifier NCT02688946.

[Is a once-daily dose of furosemide effective? Literature study into rational for dosing of short-acting diuretic]. / Is furosemide eenmaal daags wel zinvol?

- Furosemide is a widely used short-acting diuretic with a steep dose-response curve.- Furosemide is commonly prescribed once daily, but because of its short-acting nature it is questionable if a once-daily regiment is effective.- Different physiological and pathophysiological principles influence the effect and period of efficacy of furosemide.- Studies in both healthy subjects and different patient categories do demonstrate efficacy of furosemide once daily, but also that furosemide prescribed twice daily is more effective.- It is advised to combine furosemide treatment with a sodium-restricted diet, because this enhances the effects of the diuretic treatment.

The Development of Intensive Care Unit Acquired Hypernatremia Is Not Explained by Sodium Overload or Water Deficit: A Retrospective Cohort Study on Water Balance and Sodium Handling.

Background. ICU acquired hypernatremia (IAH, serum sodium concentration (sNa) ≥ 143 mmol/L) is mainly considered iatrogenic, induced by sodium overload and water deficit. Main goal of the current paper was to answer the following questions: Can the development of IAH indeed be explained by sodium intake and water balance? Or can it be explained by renal cation excretion? Methods. Two retrospective studies were conducted: a balance study in 97 ICU patients with and without IAH and a survey on renal cation excretion in 115 patients with IAH. Results. Sodium intake within the first 48 hours of ICU admission was 12.5 [9.3-17.5] g in patients without IAH (n = 50) and 15.8 [9-21.9] g in patients with IAH (n = 47), p = 0.13. Fluid balance was 2.3 [1-3.7] L and 2.5 [0.8-4.2] L, respectively, p = 0.77. Urine cation excretion (urine Na + K) was < sNa in 99 out of 115 patients with IAH. Severity of illness was the only independent variable predicting development of IAH and low cation excretion, respectively. Conclusion. IAH is not explained by sodium intake or fluid balance. Patients with IAH are characterized by low urine cation excretion, despite positive fluid balances. The current paradigm does not seem to explain IAH to the full extent and warrants further studies on sodium handling in ICU patients.

Sidestream dark field imaging of the serosal microcirculation during gastrointestinal surgery.

AIM: The study aimed to describe the serosal microcirculation of the human bowel using sidestream dark field imaging, a microscopic technique using polarized light to visualize erythrocytes through capillaries. We also compared its feasibility to the current practice of sublingual microcirculatory assessment. METHOD: In 17 patients sidestream dark field measurements were performed during gastrointestinal surgery. Microcirculatory parameters like microvascular flow index (MFI), proportion of perfused vessels (PPV), perfused vessel density (PVD) and total vessel density (TVD) were determined for every patient, sublingually and on the bowel serosa. RESULTS: Sixty measurements were done on the bowel of which eight (13%) were excluded, five owing to too much bowel peristalsis and three because of pressure artefacts. Image stability was in favour of sublingual measurements [pixel loss per image, bowel 145 (95% CI 126-164) vs sublingual 55 (95% CI 41-68); P < 0.001] and time to acquire a stable image [bowel 96 s (95% CI 63-129) vs. sublingual 46 s (95% CI 29-64); P = 0.013]. No difference in the MFI was observed [bowel 2.9 (interquartile range 2.87-2.95) vs sublingual 3.0 (interquartile range 2.91-3.0); P = 0.081]. There was a difference in the PPV [bowel 95% (95% CI 94-96) vs sublingual 97% (95% CI 97-99); P < 0.001], PVD [bowel 12.9 mm/mm2 (95% CI 11.1-14.8) vs sublingual 17.4 mm/mm2 (95% CI 15.6-19.1); P = 0.003] and the TVD [bowel 13.6 mm/mm2 (95% CI 11.6-15.6) vs sublingual 17.7 mm/mm2 (95% CI 16.0-19.4); P = 0.008]. CONCLUSION: Sidestream dark field imaging is a very promising technique for bowel microcirculatory visualization and assessment. It is comparable to sublingual assessment and the analysis produces a similar outcome with slightly differing anatomical features.

Evaluation of a vancomycin dosing protocol for intensive care unit patients.

Vancomycin is a glycopeptide antibiotic that needs to be dosed to achieve target trough levels of 15-20 mg/l. Dosing can be challenging in ICU patients. To optimise therapy, in ICU-pharmacy collaboration, a dosing protocol was introduced on the ICU of the Medical Center Leeuwarden, the Netherlands. The effectiveness in obtaining timely adequate trough levels was evaluated. We retrospectively analysed data from 59 patients. Results show that pharmacy involvement and introduction of the dosing protocol resulted in early adequate trough levels (p = 0.016). Introduction of the protocol alone resulted in non-significant early accurate trough levels. The protocol should be used with caution in patients with a possibly unreliable estimated glomerular filtration rate. Careful protocol introduction is important.

Direct markers of organ perfusion to guide fluid therapy: when to start, when to stop.

Up until now, the discussion in the literature as to the choice of fluids is almost completely restricted to the composition, with little to no attention paid to the importance of hemodynamic end points to achieve a desired optimal volume. The determination of fluid volume is left to the discretion of the attending physician with only surrogate markers as guidance the initiation and cessation of fluid therapy. In this article, we aim to discuss the available literature on existing clinical and experimental criteria for the initiation and cessation of fluid therapy. Furthermore, we present recent data that have become available after the introduction of direct in vivo microscopy of the microcirculation at the bedside, and discuss its potential influence on the existing paradigms and controversies in fluid therapy.

Microcirculatory perfusion derangements during continuous hemofiltration with fixed dose of ultrafiltration in stabilized intensive care unit patients.

INTRODUCTION: Acute kidney injury (AKI) is a well-known complication in critically ill patients. Little is known about the timing and the ultrafiltration dose after initial resuscitation. In vivo microscopy of the microcirculation has been suggested as alternative for the assessment of volume status. Previous studies contribute to the understanding that intravascular hypovolemia is reflected by microcirculatory blood flow changes not detected by conventional methods. The aim of our study was to assess microcirculatory blood flow changes during negative fluid balance ultrafiltration in patients with oliguric AKI. MATERIALS AND METHODS: Patients with oliguric AKI on renal replacement therapy were included after hemodynamic stabilization. Target was a predefined negative fluid balance; subsequently, a stepwise decrease in amount of substitution fluid was achieved. The data were recorded at baseline and after each change. RESULTS: Fifteen patients were included in the study. Microcirculatory blood flow index did not change significantly between baseline and endpoint (2.90 [2.87-3.00] vs 2.90 [2.75-3.00], P=.57). During treatment, heart rate decreased from 96 (80-111) to 94 (79-110) beats per minute (P=.01), without a significant change in mean arterial blood pressure (80 [68-95 mm Hg] vs 79 [65-91 mm Hg], P=.5). CONCLUSION: Microcirculatory blood flow is not altered by reduced substitution during renal replacement therapy.

Rectal microcirculatory alterations after elective on-pump cardiac surgery.

BACKGROUND: Hemodynamic changes, related to on-pump cardiac surgery, have been reported to impair intestinal perfusion. However, until recently, direct in vivo observation of the intestinal microcirculation was not clinically feasible, and the concept of altered intestinal blood flow in the setting of cardiac surgery depended on indirect observations from other techniques, such as tonometry and microdialysis. To establish the incidence of intestinal microvascular alterations after cardiac surgery, we performed direct in vivo observation of the microcirculation in a clinically accessible part of the intestinal tract in this setting. METHODS: A single-center prospective observational study was conducted in postoperative elective on-pump cardiac surgery patients. Simultaneously, sidestream dark field (SDF) imaging and automated gas tonometry were performed in the rectal pouch within 30 minutes after ICU admission. RESULTS: The rectal median microvascular flow index was 3(3-3) and the proportion of perfused vessels (PPV) was 85% (72-93). The median rectal-to-arterial partial carbon dioxide pressure difference (ΔPCO(2)) was 1.5 (-1.5-8.3) mmHg; 6 (21%) patients had a ΔPCO(2)> 8.3 mmHg, among them 2 (7%) with values> 10.5 mmHg. CONCLUSION: After elective on-pump cardiac surgery, direct in vivo observation of rectal mucosa revealed a PPV <90% in 54% of all patients. At the same time, rectal microcirculatory blood flow appeared to be unaltered. Combining rectal SDF imaging with rectal tonometry revealed a 7% incidence of rectal-to-arterial pCO(2) gap >1.4,kPa, suggesting non-dysoxic perfusion in the majority of patients, despite the observed percentage of non-perfused crypts.

The incidence of low venous oxygen saturation on admission to the intensive care unit: a multi-center observational study in The Netherlands.

BACKGROUND: Low mixed or central venous saturation (S(c)vO2) can reveal global tissue hypoxia and therefore can predict poor prognosis in critically ill patients. Early goal directed therapy (EGDT), aiming at an ScvO2 >/= 70%, has been shown to be a valuable strategy in patients with sepsis or septic shock and is incorporated in the Surviving Sepsis Campaign guidelines. METHODS: In this prospective observational multi-center study, we determined central venous pressure (CVP), hematocrit, pH, lactate and ScvO2 or SvO2 in a heterogeneous group of critically ill patients early after admission to the intensive care units (ICUs) in three Dutch hospitals. RESULTS: Data of 340 acutely admitted critically ill patients were collected. The mean SvO2 value was > 65% and the mean ScvO2 value was > 70%. With mean CVP of 10.3 +/- 5.5 mmHg, lactate plasma levels of 3.6 +/- 3.6 and acute physiology, age and chronic health evaluation (APACHE II) scores of 21.5 +/- 8.3, the in-hospital mortality of the total heterogeneous population was 32.0%. A subgroup of septic patients (n = 125) showed a CVP of 9.8 +/- 5.4 mmHg, mean ScvO2 values of 74.0 +/- 10.2%, where only 1% in this subgroup revealed a ScvO2 value < 50%, and lactate plasma levels of 2.7 +/- 2.2 mmol/l with APACHE II scores 20.9 +/- 7.3. Hospital mortality of this subgroup was 26%. CONCLUSION: The incidence of low ScvO2 values for acutely admitted critically ill patients is low in Dutch ICUs. This is especially true for patients with sepsis/septic shock.

Safety of citrate based hemofiltration in critically ill patients at high risk for bleeding: a comparison with nadroparin.

PURPOSE: To study the incidence and severity of bleeding in high risk critically ill patients during high volume, citrate based continuous veno-venous hemofiltration (CVVH). DESIGN: A prospective 1-year observational cohort study comparing citrate based CVVH with nadroparin based CVVH. PROCEDURES: Critically ill patients with multiple organ dysfunction and in need of CVVH were observed for bleeding complications during their CVVH sessions. Pre-defined criteria determined that patients were treated with citrate based CVVH in case of active bleeding or increased risk for bleeding. Otherwise nadroparin was used as anticoagulant. Statistical and outcome methods: The incidence of bleeding complications, the number of transfused blood cell concentrates and the filter-run-time were recorded. Analyses were made by non-parametric tests. MAIN FINDINGS: Fifty-five patients received 272 CVVH sessions. In the citrate group 14.8% experienced a bleeding complication compared to 25% in the nadroparin group (p=0.04). The number of transfused red blood cell concentrates was not different between groups. The nadroparin group had a longer filter run time (median 31.5 hours versus 22.5 hours, p=0.0001). CONCLUSIONS: In high risk critically ill patients citrate based anticoagulation for CVVH is safe in terms of bleeding complications and transfusion requirements.

Sublingual microcirculatory flow is impaired by the vasopressin-analogue terlipressin in a patient with catecholamine-resistant septic shock.

For many decades arterial blood pressure regulation has been an important issue in the treatment of septic shock. The pathogenesis of this persistent hypotension is complex and multifactorial, but inability of vascular smooth muscle to contract in the presence of vasoconstrictive agents seems to be a key factor. Many mechanisms have been proposed to account for this failure, including nitric oxide (NO) overproduction and vasopressin deficiency (1). However, improvement of outcome due to intervention in these mechanisms fails to be reported despite the restoration of blood pressure. Recent studies of the microcirculation in humans by means of orthogonal polarization spectral (OPS) imaging have opened challenging new perspectives to study the microcirculation (2, 3). We report a case in which sublingual OPS imaging was performed upon administration of terlipressin in a patient with catecholamine-resistant septic shock. It indicates that much caution should be taken when considering such potent vasoconstrictor when correcting blood pressure during shock.

Filter run time in CVVH: pre- versus post-dilution and nadroparin versus regional heparin-protamine anticoagulation.

BACKGROUND/AIMS: To study the effect of different modes of continuous veno-venous haemofiltration (CVVH) on filter run time (FRT). METHODS: We studied, in two consecutive prospective, randomised and crossover studies, 16 and 15 patients with acute renal failure during critical illness. Study A compared pre- versus post-dilution, and study B compared regional anticoagulation with heparin (pre-filter) and protamine (post-filter) (HP) versus nadroparin (NP) pre-filter. All CVVH sessions were standardised. Analyses were by Wilcoxon rank sum tests. RESULTS: Study A: During pre-dilution the median FRT was 45.7 vs. 16.1 h in post-dilution CVVH (p = 0.005). The median creatinine clearance during pre-dilution was 33 vs. 45 ml/min in post-dilution (p = 0.001). Study B: During NP, median FRT was 39.5 vs. 12.3 h during HP CVVH (p = 0.045). CONCLUSIONS: Pre-dilution CVVH results in the greatest FRT but a lower plasma creatinine clearance compared to post-dilution. Regional anticoagulation with heparin-protamine resulted in a significantly shorter FRT compared to systemic NP anticoagulation.

A before-after study of multi-resistance and cost of selective decontamination of the digestive tract.

BACKGROUND: We compared standard antibiotic use with an antibiotic policy based on selective decontamination of the digestive tract (SDD) for cost and microbiology. PATIENTS AND METHODS: A 2-year before-after observational study was performed in an 11-bed, mixed medical and surgical intensive care unit (ICU). We included all consecutive patients admitted to the ICU 1 year before and 1 year after institution of SDD (patients admitted within the 2-month SDD run-in period were excluded from analysis). In the year before SDD, 513 patients were treated in the ICU (mean APACHE II 19.5), compared to 529 in the year with SDD (mean APACHE II 19.4). RESULTS: The duration of mechanical ventilation was shorter in the SDD-treated patients (median 3, interquartile range [IQR] 2-7 days vs median 4 days, IQR 2-10, p = 0.03). The total of ICU variable costs, microbiological costs and antibiotic costs were equal in both episodes: euro 1,171 versus euro 1,168 per patient). Aerobic gram-negative bacilli (AGNB) and multiresistant AGNB were found less frequently in SDD-treated patients, RR 0.37 (95% CI 0.33-0.42) and RR 0.28 (95% CI 0.19-0.42). Multi-resistant AGNB in tracheal secretions and urine more than 72 hours after admission were completely absent in SDD-treated patients. CONCLUSION: The overall cost per patient treated during an antibiotic policy including SDD was equal to a policy supporting standard antibiotic care. In addition, duration of ventilation decreased and a trend was shown towards a decreased Length of ICU and hospital stay. Less frequently, cultures from organ sites containing AGNB were found during SDD and the number of multi-resistant strains was significantly reduced at organ sites, in particular trachea and urine. Fewer patients were colonized with multi-resistant AGNB but these numbers did not reach statistical significance.

Valproic acid intoxication: sense and non-sense of haemodialysis.

INTRODUCTION: Valproic acid is increasingly used in the treatment of epilepsy, and also prescribed for bipolar affective disorders, schizoaffective disorders, schizophrenia and migraine prophylaxis. We describe two case reports involving valproic acid intoxication with ingestion of ethanol. METHODS: One patient was treated by supportive care, one patient received haemodialysis. RESULTS: From analysis of plasma concentrations before and during haemodialysis (pre- and post-filter) it is shown that valproic acid can be effectively eliminated by haemodialysis when plasma levels are way above 100 microg/ml. In the literature, plasma protein binding is reported to be around 90% for levels within the therapeutic range. In our patient plasma protein binding was around 50% after treatment with haemodialysis. CONCLUSION: These findings make haemodialysis in valproic acid intoxication a sensible therapeutic option with increasing efficiency when plasma concentration is high. Furthermore our findings suggest that lowering valproic acid concentrations to a therapeutic level by haemodialysis does not necessarily result in an immediate, simultaneous increase in plasma protein binding of valproic acid.