Extracorporeal Albumin Dialysis in Liver Failure with MARS and SPAD: A Randomized Crossover Trial.

INTRODUCTION: Liver failure is associated with hepatic and extrahepatic organ failure leading to a high short-term mortality rate. Extracorporeal albumin dialysis (ECAD) aims to reduce albumin-bound toxins accumulated during liver failure. ECAD detoxifies blood using albumin dialysis through an artificial semipermeable membrane with recirculation (molecular adsorbent recirculating system, MARS) or without (single-pass albumin dialysis, SPAD). METHODS: We performed a randomized crossover open trial in a surgical intensive care unit. The primary outcome of the study was total bilirubin reduction during MARS and during SPAD therapies. The secondary outcomes were conjugated bilirubin and bile acid level reduction during MARS and SPAD sessions and tolerance of dialysis system devices. Inclusion criteria were adult patients presenting liver failure with factor V activity <50% associated with bilirubin ≥250 µmol/L and a complication (either hepatic encephalopathy, severe pruritus, or hepatorenal syndrome). For MARS and SPAD, the dialysis flow rate was equal to 1,000 mL/h. RESULTS: Twenty crossovers have been performed. Baseline biochemical characteristics (bilirubin, ammonia, bile acids, creatinine, and urea) were not statistically different between MARS and SPAD. Both ECAD have led to a significant reduction in total bilirubin (-83 ± 67 µmol/L after MARS; -122 ± 118 µmol/L after SPAD session), conjugated bilirubin (-82 ± 61 µmol/L after MARS; -105 ± 96 µmol/L after SPAD session), and bile acid levels (-64 ± 75 µmol/L after MARS; -56 ± 56 µmol/L after SPAD session), all nondifferent comparing MARS to SPAD. CONCLUSION: A simple-to-perform SPAD therapy with equal to MARS dialysate flow parameters provides the same efficacy in bilirubin and bile acid removal. However, clinically relevant endpoints have to be evaluated in randomized trials to compare MARS and SPAD therapies and to define the place of SPAD in the liver failure care program.

The evolution of diastolic function during liver transplantation.

INTRODUCTION: The peroperative management of liver transplantation is still associated with many cardiocirculatory complications in which diastolic dysfunction may play a contributive role. Transoesophageal echocardiography is a monitoring device commonly used in liver transplantation allowing diastolic function assessment. METHODS: We prospectively analysed the peroperative transoesophageal echocardiography recordings of 40 patients undergoing liver transplantation in order to describe changes in diastolic function at different steps of the surgery. The diastolic function marker we used was the lateral mitral annulus motion (E' wave velocity) obtained by tissue-Doppler imaging. In addition, we also studied the left ventricular filling pressure indices and systolic function. RESULTS: As a whole, there was no global change in E' wave velocity throughout the surgery. However, 11 patients (27.5%) presented a decrease in E' wave velocity up to 15% that identified an occurrence of diastolic function alteration. In this group, other peroperative data were not different from other patients (amount of bleeding, fluid administration or vasopressive support). Conversely, this group experienced lower preoperative E' wave velocity values (9cm·s-1 versus 12cm·s-1, P=0.05) and an increased incidence of postoperative cardiorespiratory complications (OR=6 [1-56], P=0.02). Considering all patients, 18 patients had an E' wave velocity under 10cm·s-1 at unclamping, characterizing a diastolic dysfunction according to the usual criteria. This dysfunction was not associated with cardiorespiratory complications. CONCLUSION: This work investigated peroperative systematic echocardiographic evaluation of diastolic function during liver transplantation. Diastolic dysfunction occurs frequently during liver transplantation and could lead to postoperative cardiorespiratory complications.

Successful modulation of portal inflow by somatostatin in a porcine model of small-for-size syndrome.

BACKGROUND: Somatostatin may prevent the small-for-size syndrome in subjects undergoing extended hepatectomy by decreasing portal pressure. METHODS: Twenty pigs underwent 70% hepatectomy (H70 group, n = 7), 90% hepatectomy (H90 group, n = 7), or sham laparotomy (control group, n = 6). Splanchnic hemodynamics was measured before and after an intraoperative infusion of somatostatin. RESULTS: The portal vein flow normalized to liver weight increased in both H70 and H90 groups (from 125 ± 42 to 342 ± 82 mL/min/100g, P = .031 and from 140 ± 46 to 530 ± 241, P = .016, respectively). The hepatic venous pressure gradient (HVPG) increased in the H90 group only (from 5.5 ± 5.8 to 13 ± 4.9 mm Hg, P = .004). Somatostatin decreased portal vein flow normalized to liver weight in both H70 and H90 groups (from 408 ± 224 to 360 ± 227 mL/min/100g, P = .031 and from 560 ± 190 to 466 ± 189 mL/min/100g, P = .016), and restored a normal HVPG in the H90 group (from 14.3 ± 4.8 to 7.7 ± 6.1 mm Hg, P = .047). CONCLUSIONS: Somatostatin restores a normal HVPG in the setting of small-for-size syndrome and can be considered as an effective pharmaceutical modality of portal inflow modulation after extended hepatectomy.

Subtotal hepatectomy in swine for studying small-for-size syndrome and portal inflow modulation: is it reliable?

BACKGROUND: Small-for-size syndrome (SFSS) is a feared complication of extended liver resection and partial liver transplantation. Swine models of extended hepatectomy have been developed for studying SFSS and its different treatment options. Although portal inflow modulation (PIM) by splenectomy or splenic artery ligation (SAL) has been proposed in humans to prevent SFSS, such procedures have not yet been evaluated in swine. OBJECTIVES: The present study was designed to evaluate modifications in splanchnic haemodynamics yielded by extended hepatectomy with and without PIM in swine. METHODS: Nineteen animals underwent 70% hepatectomy (H70, n = 7), 90% hepatectomy (H90, n = 7) or sham laparotomy (H0, n = 5). Haemodynamic measurements were performed at baseline, after hepatectomy and after PIM by SAL and splenectomy. RESULTS: Portal vein flow increased after both H70 (273 ml/min/100 g versus 123 ml/min/100 g; P = 0.016) and H90 (543 ml/min/100 g versus 124 ml/min/100 g; P = 0.031), but the hepatic venous pressure gradient (HVPG) increased only after H90 (10.0 mmHg versus 3.7 mmHg; P = 0.016). Hepatic artery flow did not significantly decrease after either H70 or H90. In all three groups, neither splenectomy nor SAL induced any changes in splanchnic haemodynamics. CONCLUSIONS: Subtotal hepatectomy of 90% in swine is a reliable model for SFSS inducing a significant increase in HVPG. However, in view of the relevant differences between swine and human splanchnic anatomy, this model is inadequate for studying the effects of PIM by SAL and splenectomy.

Point-of-care ultrasound in intensive care units: assessment of 1073 procedures in a multicentric, prospective, observational study.

OBJECTIVE: To describe current use and diagnostic and therapeutic impacts of point-of-care ultrasound (POCUS) in the intensive care unit (ICU). BACKGROUND: POCUS is of growing importance in the ICU. Several guidelines recommend its use for procedural guidance and diagnostic assessment. Nevertheless, its current use and clinical impact remain unknown. METHODS: Prospective multicentric study in 142 ICUs in France, Belgium, and Switzerland. All the POCUS procedures performed during a 24-h period were prospectively analyzed. Data regarding patient condition and the POCUS procedures were collected. Factors associated with diagnostic and therapeutic impacts were identified. RESULTS: Among 1954 patients hospitalized during the study period, 1073 (55%) POCUS/day were performed in 709 (36%) patients. POCUS served for diagnostic assessment in 932 (87%) cases and procedural guidance in 141 (13%) cases. Transthoracic echocardiography, lung ultrasound, and transcranial Doppler accounted for 51, 17, and 16% of procedures, respectively. Diagnostic and therapeutic impacts of diagnostic POCUS examinations were 84 and 69%, respectively. Ultrasound guidance was used in 54 and 15% of cases for central venous line and arterial catheter placement, respectively. Hemodynamic instability, emergency conditions, transthoracic echocardiography, and ultrasounds performed by certified intensivists themselves were independent factors affecting diagnostic or therapeutic impacts. CONCLUSIONS: With regard to guidelines, POCUS utilization for procedural guidance remains insufficient. In contrast, POCUS for diagnostic assessment is of extensive use. Its impact on both diagnosis and treatment of ICU patients seems critical. This study identified factors associated with an improved clinical value of POCUS.

Transtracheal esophageal stent removal: a case-series.

Benign esophagorespiratory fistula is a rare but often lethal affection and difficult to cure. Possible treatments are surgery or esophageal stenting but may fail and cause respiratory failure. Two patients with spontaneous esophagorespiratory fistula after chemoradiotherapy for an esophageal malignancy were both treated by esophageal exclusion but esophageal stent were left in place. The esophageal stents were transtracheally removed through the fistula. The removals were successful, patients could leave Intensive Care Unit and returned home. Transtracheal esophageal stent removal is technically possible but very risky. Such situations must be avoided: esophageal stents must absolutely be removed before esophageal exclusion.

Tacrolimus trough levels before, during and after jejunostomy in a liver transplant patient: a case report.

Although the feasibility of oral tacrolimus administration in the presence of jejunostomy has already been reported, few studies monitoring tacrolimus trough blood levels have been analyzed in detail, either during or after a jejunostomy closure. We report on our experience with a 34-year-old patient who underwent liver transplantations, with a proximal jejunostomy constructed a few days prior to the second transplantation. He was administered tacrolimus by a predominantly oral route, and less frequently received it by jejunostomy. The aim of this paper is to discuss this administration strategy and whether a different method could have been more suitable. This case report highlights that during the jejunostomy period, the tacrolimus doses that were required to maintain trough concentrations within the therapeutic range were four times higher than those administered after the closure of the jejunostomy. We observed an increase in the Dose-Normalized Trough Concentration (DNTC) values when tacrolimus was administered for 4 consecutive days by jejunostomy as compared to oral administration, indicating that the relative bioavailability of tacrolimus increased. Moreover, when returning to oral administration, the subsequent DNTC value was halved, highlighting a reduction in the tacrolimus bioavailability. Thus, in such a case, administration by jejunostomy could be more appropriate.

Impact of intra-abdominal pressure on retrohepatic vena cava shape and flow in mechanically ventilated pigs.

Conflicting results have been found regarding correlations between right atrial pressure (RAP) and inferior vena cava (IVC) diameter in mechanically ventilated patients. This finding could be related to an increase in intra-abdominal pressure (IAP). This study was designed to clarify whether variations in IVC flow rate caused by positive pressure ventilation are associated with changes in the retrohepatic IVC cross-section (ΔIVC) during major changes in volume status and IAP. Nine pigs were anesthetized, mechanically ventilated and equipped. IAP was set at 0, 15 and 30 mmHg during two conditions, i.e. normovolemia and hypovolemia, generated by blood removal to obtain a mean arterial pressure value lower than 60 mmHg. At each IAP increment, cardiac output, IVC flow and surface area were respectively assessed by flowmeters and transesophageal echocardiography. At normal IAP, even in presence of respiratory changes in IVC flows, no ΔIVC were observed during the two conditions. At high IAP, neither ΔIVC nor modulations of IVC flow were observed whatever the volemic status. The majority of animals with an IVC area of less than 0.65 cm(2) showed evidence of IAP greater than RAP values. Negative RAP-IAP pressure gradients were found to occur with an IVC area of less than 0.65 cm(2), suggesting that IVC dimensions determined using standard ultrasound techniques may indicate the direction of the RAP-IAP gradient. The clinical relevance of the present findings is that volume status should not be estimated from retrohepatic IVC dimensions in cases of high IAP.

Pulse pressure variation and stroke volume variation during increased intra-abdominal pressure: an experimental study.

INTRODUCTION: The aim of this study was to evaluate dynamic indices of fluid responsiveness in a model of intra-abdominal hypertension. METHODS: Nine mechanically-ventilated pigs underwent increased intra-abdominal pressure (IAP) by abdominal banding up to 30 mmHg and then fluid loading (FL) at this IAP. The same protocol was carried out in the same animals made hypovolemic by blood withdrawal. In both volemic conditions, dynamic indices of preload dependence were measured at baseline IAP, at 30 mmHg of IAP, and after FL. Dynamic indices involved respiratory variations in stroke volume (SVV), pulse pressure (PPV), and systolic pressure (SPV, %SPV and Δdown). Stroke volume (SV) was measured using an ultrasound transit-time flow probe placed around the aortic root. Pigs were considered to be fluid responders if their SV increased by 15% or more with FL. Indices of fluid responsiveness were compared with a Mann-Whitney U test. Then, receiver operating characteristic (ROC) curves were generated for these parameters, allowing determination of the cut-off values by using Youden's method. RESULTS: Five animals before blood withdrawal and all animals after blood withdrawal were fluid responders. Before FL, SVV (78 ± 19 vs 42 ± 17%), PPV (64 ± 18 vs 37 ± 15%), SPV (24 ± 5 vs 18 ± 3 mmHg), %SPV (24 ± 4 vs 17 ± 3%) and Δdown (13 ± 5 vs 6 ± 4 mmHg) were higher in responders than in non-responders (P < 0.05). Areas under ROC curves were 0.93 (95% confidence interval: 0.80 to 1.06), 0.89 (0.70 to 1.07), 0.90 (0.74 to 1.05), 0.92 (0.78 to 1.06), and 0.86 (0.67 to 1.06), respectively. Threshold values discriminating responders and non-responders were 67% for SVV and 41% for PPV. CONCLUSIONS: In intra-abdominal hypertension, respiratory variations in stroke volume and arterial pressure remain indicative of fluid responsiveness, even if threshold values identifying responders and non-responders might be higher than during normal intra-abdominal pressure. Further studies are required in humans to determine these thresholds in intra-abdominal hypertension.

Factors associated with noninvasive ventilation failure in postoperative acute respiratory insufficiency: an observational study.

BACKGROUND AND OBJECTIVE: Few data are available on the efficacy of noninvasive ventilation (NIV) in postoperative patients with acute respiratory failure (ARF). METHODS: Seventy-two patients coming from the surgical wards with postoperative ARF were retrospectively evaluated. The major characteristics of patients who were intubated were compared with the characteristics of those who were not after a trial of NIV. Predictive factors for failure of NIV were analysed. RESULTS: Out of 72 patients with ARF after surgery who were treated with NIV, 42 avoided intubation (58%). On a univariate analysis, a decrease in the paO2/FiO2 ratio after 1 h of NIV (223 +/- 84 to 160 +/- 68 mmHg, P < 0.05) was associated with NIV failure and need for tracheal intubation because of nosocomial pneumonia and an increased simplified acute physiology score (SAPS) 2. In a multivariate analysis, nosocomial pneumonia [odds ratio (OR) 4.189; 95% confidence interval (CI) 1.383-12.687] and SAPS 2 higher than 35 (OR 4.969; 95% CI 1.627-15.172) were independent predictive factors of NIV failure. NIV success was associated with a reduced ICU stay (16.8 vs. 26.1 days, P < 0.001). CONCLUSION: NIV could be considered in postoperative patients who presented with ARF. Nosocomial pneumonia is predictive of NIV failure.

Increased intra-abdominal pressure affects respiratory variations in arterial pressure in normovolaemic and hypovolaemic mechanically ventilated healthy pigs.

OBJECTIVE: To evaluate the effect of increased intra-abdominal pressure (IAP) on the systolic and pulse pressure variations induced by positive pressure ventilation in a porcine model. DESIGN AND SETTING: Experimental study in a research laboratory. SUBJECTS: Seven mechanically ventilated and instrumented pigs prone to normovolaemia and hypovolaemia by blood withdrawal. INTERVENTION: Abdominal banding gradually increased IAP in 5-mmHg steps up to 30 mmHg. MEASUREMENTS AND MAIN RESULTS: Variations in systolic pressure, pulse pressure, inferior vena cava flow, and pleural and transmural (LVEDPtm) left-ventricular end-diastolic pressure were recorded at each step. Systolic pressure variations were 6.1+/-3.1%, 8.5+/-3.6% and 16.0+/-5.0% at 0, 10, and 30 mmHg IAP in normovolaemic animals (mean+/-SD; p<0.01 for IAP effect). They were 12.7+/-4.6%, 13.4+/-6.7%, and 23.4+/-6.3% in hypovolaemic animals (p<0.01 vs normovolaemic group) for the same IAP. Fluctuations of the inferior vena cava flow disappeared as the IAP increased. Breath cycle did not induce any variations of LVEDPtm for 0 and 30 mmHg IAP. CONCLUSIONS: In this model, the systolic pressure and pulse pressure variations, and inferior vena cava flow fluctuations were dependent on IAP values which caused changes in pleural pressure swing, and this dependency was more marked during hypovolaemia. The present study suggests that dynamic indices are not exclusively related to volaemia in the presence of increased IAP. However, their fluid responsiveness predictive value could not be ascertained as no fluid challenge was performed.

Risk factors for piperacillin/tazobactam-resistant Escherichia coli in ICU patients: a clinical study.

OBJECTIVE: To determine risk factors of infections with piperacillin/tazobactam-resistant Escherichia coli in critical care patients. DESIGN: Prospective, consecutive sample survey study. SETTING: Surgical intensive care unit (ICU) in a university hospital. PATIENTS: A consecutive series of 133 patients from whom culture results were positive for E. coli during their ICU stay. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Multivariate logistic regression analysis identified the following significant independent factors associated with the emergence of a piperacillin/tazobactam-resistant Escherichia coli: prior use of amoxicillin (odds ratio, 4.15) and amoxicillin/clavulanate (odds ratio, 3.25). CONCLUSIONS: Treatment with amoxicillin or amoxicillin/clavulanate is a major risk factor for the detection of piperacillin/tazobactam-resistant E. coli in ICU patients.