RBC Transfusion in Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study.

OBJECTIVES: In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation. DESIGN: Mixed method approach combining multicenter retrospective study and survey. SETTING: Sixteen ICUs worldwide. PATIENTS: Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45-62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5-14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8 g/dL (8.9-13.0 g/dL), decreasing to 8.7 g/dL (7.7-9.8 g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1 g/dL [7.4-9.3 g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3-2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9 g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients. CONCLUSIONS: Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation.

Hyperammonemia during treatment with valproate in critically ill patients.

INTRODUCTION: Hyperammonemia (HA) is a potential side-effect of valproate (VPA) treatment, which has been described during long-term administration. The aim of this study was to evaluate the incidence, the impact and the risk factors of HA in critically ill patients. METHODS: We reviewed the data of all adult patients treated in our mixed 35-bed Department of Intensive Care over a 12-year period (2004-2015) who: a) were treated with VPA for more than 72 h and b) had at least one measurement of ammonium and VPA levels during the ICU stay; patients with Child-Pugh C liver cirrhosis were excluded. HA was defined as ammonium levels above 60 µg/dl. RESULTS: Of a total of 2640 patients treated with VPA, 319 patients met the inclusion criteria (median age 64 years; male gender 55%); 78% of them were admitted for neurological reasons and ICU mortality was 30%. Median ammonium levels were 88 [63-118] µg/dl. HA was found in 245 (77%) patients. For those patients with HA, median time from start of VPA therapy to HA was 3 [2-5] days. In a multivariable analysis, high VPA serum levels, mechanical ventilation and sepsis were independently associated with HA during VPA therapy. In 98/243 (40%) of HA patients, VPA was interrupted; VPA interruption was more frequent in patients with ammonium levels > 100 µg/dl than others (p = 0.001). HA was not an independent predictor of ICU mortality or poor neurological outcome. CONCLUSIONS: In this study, HA was a common finding during treatment with VPA in acutely ill patients. VPA levels, sepsis and mechanical ventilation were risk factors for HA. Hyperammonemia did not influence patients' outcome.

Prediction of Insufficient Beta-Lactam Concentrations in Extracorporeal Membranous Oxygenation Patients.

BACKGROUND: The aim of this study was to identify predictors of insufficient beta-lactam concentrations in patients undergoing extracorporeal membrane oxygenation (ECMO). METHODS: Retrospective analysis of all patients receiving ECMO support and treated with ceftazidime or cefepime (CEF), piperacillin/tazobactam (TZP), or meropenem (MEM). Trough drug concentrations (Cmin) were measured before the subsequent dose, according to the decision of the attending physician. Insufficient drug concentrations were identified if Cmin was below the clinical breakpoint of Pseudomonas aeruginosa. RESULTS: A total of 222 Cmin (CEF, n = 41; TZP, n = 85; MEM, n = 96) from 110 patients were included; insufficient concentrations were observed in 26 (12%) antibiotic assessments; 21 (81%) of those occurred during MEM therapy. Insufficient Cmin were associated with a shorter time from initiation of antibiotics to measurement, a lower single dose of antibiotic, a higher creatinine clearance (CrCL), lower sequential organ failure assessment (SOFA) scores, and less use of continuous renal replacement therapy (CRRT) when compared to others. CONCLUSIONS: Insufficient broad-spectrum beta-lactam concentrations were observed in 12% of drug measurement during ECMO therapy. Higher than recommended drug regimens could be considered in the very early phase of therapy and in those patients with augmented renal clearance and with less severe organ dysfunction.

Six-Month Pulmonary Function After Venovenous Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019 Patients.

OBJECTIVES: Venovenous extracorporeal membrane oxygenation has been largely used in patients with refractory acute respiratory distress syndrome due to coronavirus disease 2019. Few data on long-term pulmonary function among venovenous extracorporeal membrane oxygenation survivors are available. DESIGN: Retrospective, observational cohort. SETTING: Two mixed medical-surgical tertiary (30 beds) and secondary (22 beds) ICUs. PATIENTS: All critically ill adult coronavirus disease 2019 survivors treated with venovenous extracorporeal membrane oxygenation between March 10, and April 30, 2020. MEASUREMENTS AND MAIN RESULTS: The last available lung function and 6-minute walking tests, performed after a median of 178 days (ranges, 72-232 d) from ICU admission, were analyzed. Among the 32 coronavirus disease 2019 patients treated by venovenous extracorporeal membrane oxygenation during the study period, 11 (34%; median age 56 yr; median duration of mechanical ventilation and extracorporeal membrane oxygenation therapy of 26 and 15 d, respectively) were successfully weaned and discharged home. Spirometry was performed in nine patients; the volumetric lung function was preserved, that is, median forced vital capacity was 83% of predicted value (51-99% of predicted value), and median forced expiratory volume in 1 second was 82% of predicted value (60-99% of predicted value). Also, the median residual volume and the lung capacity were 100% of predicted value (50-140% of predicted value) and 90% of predicted value (50-100% of predicted value); only the diffusion capacity of the lung for carbon monoxide and 6-minute walking test were decreased (58% of predicted value [37-95% of predicted value] and 468 meters (365-625 meters), corresponding to [63-90% of predicted value], respectively). CONCLUSIONS: Among survivors from severe coronavirus disease 2019 pneumonia treated with venovenous extracorporeal membrane oxygenation, preserved long-term volumetric lung function with decreased diffusion capacity of lung carbon monoxide was observed.

Hemoadsorption to treat severe iatrogenic intoxication with Patent Blue: a case report.

BACKGROUND: Intoxication with Patent Blue V [sodium compound of (diethylamino-4-phenyl)(hydroxy-5-disulfo-2,4-phenyl) methanol] can lead to high levels of methemoglobin and metabolic acidosis. In severe cases and if not rapidly eliminated from the plasma, this can lead to multiple organ failure and death. CASE REPORT: A 27-year-old Asian woman (original from Vietnam) was admitted after ecstasy intoxication resulting in multi-organ failure (acute respiratory distress syndrome, metabolic acidosis, capillary leakage syndrome, renal failure, shock refractory to standard resuscitation). As a consequence, continuous renal replacement therapy and veno-venous extracorporeal membrane oxygenation were started. Methylene blue administration to reverse vasoplegia was decided, but unfortunately, Patent Blue V was erroneously administered, resulting in a severe clinical picture of methemoglobinemia and tissue hypoxia. As a therapeutic intervention, CytoSorb hemoadsorption was initiated, and rapid and significant reduction in plasma methemoglobin, accompanied by improved hemodynamics and normalization in plasma lactate levels, was observed. CONCLUSIONS: This is the first case describing the application of CytoSorb hemoadsorption in a patient with ecstasy intoxication complicated by iatrogenic administration of Patent Blue V. There is a potential role for CytoSorb in drug intoxication, which needs to be confirmed in larger series.

Comparison of antemortem clinical diagnosis and post-mortem findings in intensive care unit patients.

Autopsy is an important quality assurance indicator and a tool to advance medical knowledge. This study aims to compare the premortem clinical and postmortem pathology findings in patients who died in the Intensive Care Unit (ICU), to analyze if there are any discrepancies between them, and to compare the results to two similar studies performed in our institution in 2004 and 2007. Between January 1, 2016, and December 31, 2018, 888 patients died in the ICU and 473 underwent post-mortem examination (PME) of whom 437 were included in the present study. Autopsies revealed discrepancies between clinical diagnosis and pathologic findings according to in 101 cases (23.1%) according to Goldman classification. Forty-eight major discrepancies (class I and class II) were identified in 44 cases and the most frequent identified discrepancies were pulmonary embolism (3/12) as class I and malignancies (13/35) as class II. They were more frequent in patients hospitalized for less than 10 days then in the group with more than 10 days of hospitalization (13.8% vs 4.5%; p = 0.002). No statistical difference has been noticed concerning age, gender, and ICU stay. We observed an increase of performed autopsies and a total discrepancy rate similar to the studies performed in the same institution in 2004 (22.5%) and 2007 (21%). In conclusion, discrepancies between clinical and PME diagnoses persist despite the medical progress. Secondly, the autopsy after a short hospital stay may reveal unexpected findings whose diagnosis is challenging even if it may be suspected by the intensivist.

The Acquisition of Multidrug-Resistant Bacteria in Patients Admitted to COVID-19 Intensive Care Units: A Monocentric Retrospective Case Control Study.

Whether the risk of multidrug-resistant bacteria (MDRB) acquisition in the intensive care unit (ICU) is modified by the COVID-19 crisis is unknown. In this single center case control study, we measured the rate of MDRB acquisition in patients admitted in COVID-19 ICU and compared it with patients admitted in the same ICU for subarachnoid hemorrhage (controls) matched 1:1 on length of ICU stay and mechanical ventilation. All patients were systematically and repeatedly screened for MDRB carriage. We compared the rate of MDRB acquisition in COVID-19 patients and in control using a competing risk analysis. Of note, although we tried to match COVID-19 patients with septic shock patients, we were unable due to the longer stay of COVID-19 patients. Among 72 patients admitted to the COVID-19 ICUs, 33% acquired 31 MDRB during ICU stay. The incidence density of MDRB acquisition was 30/1000 patient days. Antimicrobial therapy and exposure time were associated with higher rate of MDRB acquisition. Among the 72 SAH patients, 21% acquired MDRB, with an incidence density was 18/1000 patient days. The septic patients had more comorbidities and a greater number of previous hospitalizations than the COVID-19 patients. The incidence density of MDRB acquisition was 30/1000 patient days. The association between COVID-19 and MDRB acquisition (compared to control) risk did not reach statistical significance in the multivariable competing risk analysis (sHR 1.71 (CI 95% 0.93-3.21)). Thus, we conclude that, despite strong physical isolation, acquisition rate of MDRB in ICU patients was at least similar during the COVID-19 first wave compared to previous period.

Electroencephalographic features in patients undergoing extracorporeal membrane oxygenation.

BACKGROUND: Neurologic injury is one of the most frequent causes of death in patients undergoing extracorporeal membrane oxygenation (ECMO). As neurological examination is often unreliable in sedated patients, additional neuromonitoring is needed. However, the value of electroencephalogram (EEG) in adult ECMO patients has not been well assessed. Therefore, the aim of this study was to assess the occurrence of electroencephalographic abnormalities in patients treated with extracorporeal membrane oxygenation (ECMO) and their association with 3-month neurologic outcome. METHODS: Retrospective analysis of all patients undergoing venous-venous (V-V) or venous-arterial (V-A) ECMO with a concomitant EEG recording (April 2009-December 2018), either recorded intermittently or continuously. EEG background was classified into four categories: mild/moderate encephalopathy (i.e., mostly defined by the presence of reactivity), severe encephalopathy (mostly defined by the absence of reactivity), burst-suppression (BS) and suppressed background. Epileptiform activity (i.e., ictal EEG pattern, sporadic epileptiform discharges or periodic discharges) and asymmetry were also reported. EEG findings were analyzed according to unfavorable neurological outcome (UO, defined as Glasgow Outcome Scale < 4) at 3 months after discharge. RESULTS: A total of 139 patients (54 [41-62] years; 60 (43%) male gender) out of 596 met the inclusion criteria and were analyzed. Veno-arterial (V-A) ECMO was used in 98 (71%); UO occurred in 99 (71%) patients. Continuous EEG was performed in 113 (81%) patients. The analysis of EEG background showed that 29 (21%) patients had severe encephalopathy, 4 (3%) had BS and 19 (14%) a suppressed background. In addition, 11 (8%) of patients had seizures or status epilepticus, 10 (7%) had generalized periodic discharges or lateralized periodic discharges, and 27 (19%) had asymmetry on EEG. In the multivariate analysis, the occurrence of ischemic stroke or intracranial hemorrhage (OR 4.57 [1.25-16.74]; p = 0.02) and a suppressed background (OR 10.08 [1.24-82.20]; p = 0.03) were independently associated with UO. After an adjustment for covariates, an increasing probability for UO was observed with more severe EEG background categories. CONCLUSIONS: In adult patients treated with ECMO, EEG can identify patients with a high likelihood of poor outcome. In particular, suppressed background was independently associated with unfavorable neurological outcome.

Higher Intensity Thromboprophylaxis Regimens and Pulmonary Embolism in Critically Ill Coronavirus Disease 2019 Patients.

OBJECTIVES: To assess the role of thromboprophylaxis regimens on the occurrence of pulmonary embolism in coronavirus disease 2019 patients. DESIGN: Retrospective analysis of prospectively collected data on coronavirus disease 2019 patients, included between March 10, and April 30, 2020. SETTING: ICU of an University Hospital in Belgium. PATIENTS AND INTERVENTIONS: Critically ill adult mechanically ventilated coronavirus disease 2019 patients were eligible if they underwent a CT pulmonary angiography, as part of the routine management in case of persistent hypoxemia or respiratory deterioration. The primary endpoint of this study was the occurrence of pulmonary embolism according to the use of standard thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units once daily) or high regimen thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units bid or therapeutic unfractioned heparin). MEASUREMENTS AND MAIN RESULTS: Of 49 mechanically ventilated coronavirus disease 2019, 40 underwent CT pulmonary angiography after a median of 7 days (4-8 d) since ICU admission and 12 days (9-16 d) days since the onset of symptoms. Thirteen patients (33%) were diagnosed of pulmonary embolism, which was bilateral in six patients and localized in the right lung in seven patients. D-dimers on the day of CT pulmonary angiography had a predictive accuracy of 0.90 (95% CIs: 0.78-1.00) for pulmonary embolism. The use of high-regimen thromboprophylaxis was associated with a lower occurrence of pulmonary embolism (2/18; 11%) than standard regimen (11/22, 50%-odds ratio 0.13 [0.02-0.69]; p = 0.02); this difference remained significant even after adjustment for confounders. Six patients with pulmonary embolism (46%) and 14 patients without pulmonary embolism (52%) died at ICU discharge (odds ratio 0.79 [0.24-3.26]; p = 0.99). CONCLUSIONS: In this study, one third of coronavirus disease 2019 mechanically ventilated patients have a pulmonary embolism visible on CT pulmonary angiography. High regimen thromboprophylaxis may decrease the occurrence of such complication.

Comparison of extracorporeal and conventional cardiopulmonary resuscitation: a retrospective propensity score matched study.

BACKGROUND: The potential benefit of extracorporeal cardiopulmonary resuscitation (ECPR) compared to conventional CPR (CCPR) for patients with refractory cardiac arrest (CA) remains unclear. METHODS: This study is a retrospective analysis of a prospective database of CA patients, which includes all consecutive adult patients admitted to the Department of Intensive Care after CA between January 2012 and December 2017. The decision to initiate ECPR was made by the attending physician and ECPR performed by the ECPR team, which is composed of ICU physicians. A propensity score was derived using a logistic regression model, including characteristics that varied between groups with a p <  0.10 and were potentially related to outcome. Primary outcomes were survival to ICU discharge and favorable 3-month neurologic outcome, assessed by a Cerebral Performance Category (CPC) score of 1-2. RESULTS: From a total of 635 patients with CA during the study period (ECPR, n = 112), 80 ECPR patients were matched to 80 CCPR patients. The time from arrest to termination of CPR (i.e., return of spontaneous circulation [ROSC], extracorporeal membrane oxygenation [ECMO] initiation, or death) was 54 ± 22 and 54 ± 19 min in the ECPR and CCPR groups, respectively. ROSC rates were 77/80 (96%) for ECPR and 30/80 (38%) for CCPR (p <  0.001). Survival to ICU discharge was 18/80 (23%) vs. 14/80 (18%) in the ECPR and CCPR groups, respectively (p = 0.42). At 3 months, 17/80 (21%) ECPR patients and 9/80 (11%) CCPR patients had a favorable outcome (p = 0.11). Cox regression analysis stratified by matched pairs showed a significantly higher neurologic outcome rate in the ECPR group than in the CCPR group (log-rank test p = 0.003). CONCLUSIONS: ECPR after CA may be associated with improved long-term neurological outcome.

Hybrid extracorporeal membrane oxygenation.

Veno-venous (VV) and veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) therapy is widely used in critically ill patients with refractory cardiogenic shock and cardiac arrest or suffering from severe respiratory failure. Besides traditional ECMO cannulation, changes in patients' conditions or the occurrence of specific complications (i.e., cerebral hypoxia or left ventricular dilation) may require modifications in cannulation strategies or the combination of ECMO with additional invasive or minimally invasive procedures, to improve organ function and ECMO efficiency. In this review, we described all these "hybrid" approaches, such as the addition of a third or fourth ECMO cannula to improve venous drainage and/or optimize systemic hemodynamics/oxygenation, or the implementation of surgical or percutaneous unloading of the left ventricle (LV), to reduce cardiac dilation and pulmonary edema. Although few data are still available about the effectiveness of such interventions, clinicians should be aware of these advances in ECMO management to improve the management of more complex cases.

Cerebral Near-Infrared Spectroscopy in Adult Patients Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Acute cerebral complications (ACC) of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are associated with poor long-term neurologic outcome. We described the role of rSO2 monitoring in detecting ACC and desaturations and their relationship with poor outcome when employing VA-ECMO. METHODS: Retrospective analysis of patients monitored by cerebral frontal near-infrared spectroscopy (NIRS) (CAS Medical Systems Inc., Branford, CT, USA) during VA-ECMO (November 2008-December 2015). ACC was defined as the presence of stroke and/or brain death, while cerebral desaturation as cortical oxygen tissue saturation (rSO2) < 60%. RESULTS: Fifty-six of 159 VA-ECMO patients (age 55 [36-60] years) were included; 18 (32%) developed ACC and 36 died (64%). Cerebral desaturation occurred in 43 (74%) patients, who had a higher mortality than those without cerebral desaturation (74 vs. 31%). A high sequential organ failure assessment (SOFA) score on the first day of ECMO (OR 1.40 [95% CIs 1.06-1.84]) and the minimum ECMO blood flow during the first 4 days of therapy (OR 3.05 [1.01-9.17]) were independently associated with the occurrence of cerebral desaturation. Cerebral desaturation occurred more frequently in patients with ACC than others (94 vs. 68%); patients with ACC also had a lower minimal rSO2 over time (49 vs. 54%) and more frequently had high right-left rSO2 differences (33 vs. 8%), which were both independent predictors of ACC. The occurrence of cerebral desaturation (OR 7.93 [1.62-38.74]) and high lactate concentrations during the first 4 days of ECMO support (OR 1.22 [1.03-1.46]) was independently associated with hospital mortality. CONCLUSIONS: Monitoring of rSO2 could be considered as an interesting tool to monitor the brain of patients on VA-ECMO.

Manual versus Automated moNitoring Accuracy of GlucosE II (MANAGE II).

BACKGROUND: Intravascular continuous glucose monitoring (CGM) may facilitate glycemic control in the intensive care unit (ICU). We compared the accuracy of a CGM device (OptiScanner®) with a standard reference method. METHODS: Adult patients who had blood glucose (BG) levels >150 mg/dl and required insertion of an arterial and central venous catheter were included. The OptiScanner® was inserted into a multiple-lumen central venous catheter. Patients were treated using a dynamic-scale insulin algorithm to achieve BG values between 80 and 150 mg/dl. The BG values measured by the OptiScanner® were plotted against BG values measured using a reference analyzer. The correlation between the BG values measured using the two methods and the clinical relevance of any differences were assessed using the coefficient of determination (r 2) and the Clarke error grid, respectively; bias was assessed by the mean absolute relative difference (MARD). Three different standards of glucose monitoring were used to assess accuracy. Glycemic control was assessed using the time in range (TIR). Six indices of glycemic variability were calculated. RESULTS: The analysis included 929 paired samples from 88 patients, monitored for a total of 2584 hours. Reference BG values ranged between 60 and 484 mg/dl. The r 2 value was 0.89. The percentage of BG values within zones A and B of the Clarke error grid was 99.9%; the MARD was 7.7%. Using the ISO 15197 standard and Food and Drug Administration and consensus standards, respectively, 80.4% of measurements were within 15 mg/dl and 88.2% within 15% of reference values, 40% of measurements were within 7 mg/dl and 72.5% within 10% of reference values, and 65.2% of measurements were within 10 mg/dl and 82.7% within 12.5% of reference values. The TIR was slightly lower with the OptiScanner® than with the reference method. The J-index, standard deviation and maximal glucose change were the indices of glycemic variability least affected by the measurement device. CONCLUSIONS: Based on the MARD, the performance of the OptiScanner® is adequate for use in ICU patients. Because recent standards for accuracy were not met, the OptiScanner® should not be used as a sole monitor. The assessment of glycemic variability is influenced by the time interval between BG determinations. TRIAL REGISTRATION: Clinicaltrials.gov NCT01720381 . Registered 31 October 2012.

A high-dose aminoglycoside regimen combined with renal replacement therapy for the treatment of MDR pathogens: a proof-of-concept study.

BACKGROUND: Infections caused by MDR Gram-negative (GN) organisms in critically ill patients are a therapeutic challenge. The administration of high-dose aminoglycoside (HDA) therapy coupled with high-flow continuous veno-venous haemodiafiltration (CVVHDF) could allow required high drug peaks to be achieved with acceptable drug elimination. METHODS: All adult patients present on the ICU between October 2009 and July 2014 who had MDR GN sepsis were considered for HDA and high-flow (>45 mL/kg/h) CVVHDF when an isolated pathogen was susceptible or had intermediate susceptibility to aminoglycosides and the patient's condition was not improving with conventional therapy. Optimal antibacterial activity was defined as a peak concentration of at least eight times the MIC. RESULTS: Fifteen patients infected with MDR GN pathogens (11 with Pseudomonas aeruginosa; 10 with abdominal infections and 5 with respiratory infections) were treated with amikacin (n = 11), gentamicin (n = 3) or tobramycin (n = 1) and high-flow CVVHDF. A favourable clinical response was observed in eight (53%) patients, including three in whom microbial eradication was obtained. Six patients were discharged alive from the ICU, and five from the hospital. No renal toxicity was observed among survivors. CONCLUSION: In this cohort of septic patients with MDR GN infections, HDA combined with high-flow CVVHDF represented a valuable therapeutic option. The effectiveness of this approach should be further evaluated in larger studies.

Effects of fluid administration on renal perfusion in critically ill patients.

INTRODUCTION: Fluid administration is a first-line therapy for acute kidney injury associated with circulatory failure. Although aimed at increasing renal perfusion in these patients, this intervention may improve systemic hemodynamics without necessarily ameliorating intrarenal flow distribution or urine output. We used Doppler techniques to investigate the effects of fluid administration on intrarenal hemodynamics and the relationship between changes in renal hemodynamics and urine output. We hypothesized that, compared to systemic hemodynamic variables, changes in renal hemodynamics would better predict increase in urine output after fluid therapy. METHODS: We measured systemic hemodynamic variables and performed renal interlobar artery Doppler on both kidneys before and after volume expansion in 49 adult patients with acute circulatory failure. We measured systolic and diastolic velocities and computed the resistivity index (RI). We recorded urine output for 3 h before and after the fluid challenge. RESULTS: Fluid administration resulted in a small but consistent decrease in RI (from 0.73 ± 0.09 to 0.71 ± 0.09, p < 0.01). There was a concomitant increase in mean arterial pressure (from 75 ± 15 to 80 ± 14 mmHg, p < 0.01), pulse pressure (49 ± 19 to 55 ± 19 mmHg, p < 0.01) and urine output (55 ± 76 to 81 ± 87 ml/hour, p < 0.01). Changes in RI were negatively correlated with changes in urine output and mean arterial pressure but not in pulse pressure. The increase in urine output was predicted by changes in RI but not by changes in systemic hemodynamics. CONCLUSIONS: Changes in renal hemodynamics during a fluid challenge can be observed by Doppler ultrasonography before urine output increases. Moreover, these changes are better predictors of an increase in urine output than are mean arterial pressure and pulse pressure.

Comparison of dopamine and norepinephrine in the treatment of shock.

BACKGROUND: Both dopamine and norepinephrine are recommended as first-line vasopressor agents in the treatment of shock. There is a continuing controversy about whether one agent is superior to the other. METHODS: In this multicenter, randomized trial, we assigned patients with shock to receive either dopamine or norepinephrine as first-line vasopressor therapy to restore and maintain blood pressure. When blood pressure could not be maintained with a dose of 20 microg per kilogram of body weight per minute for dopamine or a dose of 0.19 microg per kilogram per minute for norepinephrine, open-label norepinephrine, epinephrine, or vasopressin could be added. The primary outcome was the rate of death at 28 days after randomization; secondary end points included the number of days without need for organ support and the occurrence of adverse events. RESULTS: The trial included 1679 patients, of whom 858 were assigned to dopamine and 821 to norepinephrine. The baseline characteristics of the groups were similar. There was no significant between-group difference in the rate of death at 28 days (52.5% in the dopamine group and 48.5% in the norepinephrine group; odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P=0.10). However, there were more arrhythmic events among the patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P<0.001). A subgroup analysis showed that dopamine, as compared with norepinephrine, was associated with an increased rate of death at 28 days among the 280 patients with cardiogenic shock but not among the 1044 patients with septic shock or the 263 with hypovolemic shock (P=0.03 for cardiogenic shock, P=0.19 for septic shock, and P=0.84 for hypovolemic shock, in Kaplan-Meier analyses). CONCLUSIONS: Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events. (ClinicalTrials.gov number, NCT00314704.)