Changes in pulse pressure variation to assess preload responsiveness in mechanically ventilated patients with spontaneous breathing activity: an observational study.

BACKGROUND: Pulse pressure variation (PPV) is not reliable in predicting preload responsiveness in patients receiving mechanical with spontaneous breathing (SB) activity. We hypothesised that an increase in PPV after a tidal volume (VT) challenge (TVC) or a decrease in PPV during passive leg raising (PLR) can predict preload responsiveness in such cases. METHODS: This prospective observational study was performed in two ICUs and included patients receiving mechanical ventilation with SB, for whom the treating physician decided to test preload responsiveness. Transthoracic echocardiography was used to measure the velocity-time integral (VTI) of the left ventricular outflow tract. Patients exhibiting an increase in VTI ≥12% during PLR were defined as PLR+ patients (or preload responders). Then, a TVC was performed by increasing VT by 2 ml kg-1 predicted body weight (PBW) for 1 min. PPV was recorded at each step. RESULTS: Fifty-four patients (Simplified Acute Physiology Score II: 60 (25) ventilated with a VT of 6.5 (0.8) ml kg-1 PBW, were included. Twenty-two patients were PLR+. The absolute decrease in PPV during PLR and the absolute increase in PPV during TVC discriminated between PLR+ and PLR- patients with area under the receiver operating characteristic (AUROC) curve of 0.78 and 0.73, respectively, and cut-off values of -1% and +2%, respectively. Those AUROC curve values were similar but were significantly different from that of baseline PPV (0.61). CONCLUSION: In patients undergoing mechanical ventilation with SB activity, PPV does not predict preload responsiveness. However, the decrease in PPV during PLR and the increase in PPV during a TVC help discriminate preload responders from non-responders with moderate accuracy. CLINICAL TRIAL REGISTRATION: NCT04369027 (ClinicalTrials.gov).

Increase in Central Venous Pressure During Passive Leg Raising Cannot Detect Preload Unresponsiveness.

OBJECTIVE: By analogy with the classical central venous pressure rules to assess a fluid challenge, we hypothesized that an increase in central venous pressure greater than or equal to 5 cm H2O (i.e., 4 mm Hg) during passive leg raising can predict preload unresponsiveness diagnosed by the absence of increase in velocity-time integral of the left ventricular outflow tract greater than or equal to 10% during the test (negative passive leg raising test). DESIGN AND SETTINGS: Velocity-time integral was measured by transthoracic echocardiography. Central venous pressure and velocity-time integral were measured before and during passive leg raising. PATIENTS: Critically ill patients for whom the physician decided to test preload responsiveness by passive leg raising were prospectively included. MEASUREMENT AND MAIN RESULTS: Fifty-seven set of measurements were performed in 50 patients. Preload unresponsiveness (negative passive leg raising test) was observed in 32 cases. The changes in central venous pressure during passive leg raising did not differ between positive passive leg raising cases (positive passive leg raising test) and negative passive leg raising test cases (3 ± 2 vs 3 ± 2 mm Hg, respectively) and thus did not predict preload unresponsiveness (area under the receiver-operating characteristic curve of 0.59). An increase in central venous pressure greater than or equal to 4 mm Hg during passive leg raising was observed in 10 cases of positive passive leg raising test and in 11 cases of negative passive leg raising test. Taking an increase in central venous pressure greater than or equal to 3 or greater than or equal to 5 mm Hg rather than greater than or equal to 4 mm Hg during passive leg raising did not better allow one to identify negative passive leg raising test. CONCLUSIONS: Marked increase in central venous pressure during passive leg raising cannot identify negative passive leg raising test cases and thus preload unresponsiveness. Measurements of cardiac output (or its surrogates) during passive leg raising are, thus, mandatory to appropriately interpret this test.

Urgent Chemotherapy for Life-Threatening Complications Related to Solid Neoplasms.

OBJECTIVES: Solid neoplasms can be directly responsible for organ failures at the time of diagnosis or relapse. The management of such specific complications relies on urgent chemotherapy and eventual instrumental or surgical procedures, combined with advanced life support. We conducted a multicenter study to address the prognosis of this condition. DESIGN: A multicenter retrospective (2001-2015) chart review. SETTING: Medical and respiratory ICUs. PATIENTS: Adult patients who received urgent chemotherapy in the ICU for organ failure related to solid neoplasms were included. The modalities of chemotherapy, requirements of adjuvant instrumental or surgical procedures, and organ supports were collected. Endpoints were short- and long-term survival rates. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-six patients were included. Lung cancer was the most common malignancy distributed into small cell lung cancer (n = 57) and non-small cell lung cancer (n = 33). The main reason for ICU admission was acute respiratory failure in 111 patients (81.6%), of whom 89 required invasive mechanical ventilation. Compression and tissue infiltration by tumor cells were the leading mechanisms resulting in organ involvement in 78 (57.4%) and 47 (34.6%) patients. The overall in-ICU, in-hospital, 6-month, and 1-year mortality rates were 37%, 58%, 74%, and 88%, respectively. Small cell lung cancer was identified as an independent predictor of hospital survival. However, this gain in survival was not sustained since the 1-year survival rates of small cell lung cancer, non-small cell lung cancer, and non-lung cancer patients all dropped below 20%. CONCLUSIONS: Urgent chemotherapy along with aggressive management of organ failures in the ICU can be lifesaving in very selected cancer patients, most especially with small cell lung cancer, although the long-term survival is hardly sustainable.

Renal replacement therapy in patients with severe precapillary pulmonary hypertension with acute right heart failure.

BACKGROUND: Renal replacement therapy has been suggested as a therapeutic option in the setting of acute right ventricular failure in patients with severe precapillary pulmonary hypertension. However, there are few data supporting this strategy. OBJECTIVES: To describe the clinical course and the prognosis of pulmonary hypertensive patients undergoing renal replacement therapy in the setting of acute right heart failure. METHODS: This was a single-center retrospective study over an 11-year period. Data were collected from all patients with chronic precapillary pulmonary hypertension requiring catecholamine infusions for clinical worsening and acute kidney injury that necessitated renal replacement therapy. RESULTS: Fourteen patients were included. At admission, patients had a blood urea of 28.2 mmol/l (22.3-41.2), a creatinine level of 496 µmol/l (304-590), and a mean urine output in the 24 h preceding hospitalization of 200 ml (0-650). Sixty-eight renal replacement therapy sessions were performed, 36 of which were continuous and 32 of which were intermittent. Systemic hypotension occurred in 16/32 intermittent and 16/36 continuous sessions (p = 0.9). Two patients died during a continuous session. The intensive care unit-related, 1-, and 3-month mortality was 46.7, 66.7, and 73.3%, respectively. CONCLUSION: Renal replacement therapy is feasible in the setting of acute right ventricular failure in patients with severe precapillary pulmonary hypertension but is associated with a poor prognosis. The best modality and timing in this population remain to be defined.

Validation of the new Complior sensor to record pressure signals non-invasively.

The Complior device (Alam Medical, France) has contributed to the rise of arterial stiffness as a measure of cardiovascular risk. In its latest version (Complior Analyse) the sensor records pressure instead of distension waveforms thus allowing the measurement of central pressure and pulse wave analysis. The aim of our study was to verify that the new sensor measures pressure waveforms accurately in both time and frequency domain. Invasive and non-invasive signals were recorded simultaneously at the radial artery and compared in the frequency and time domain in haemodynamically stable intensive care unit patients. Twelve patients entered the study (8 men, 4 women, mean age 69 ± 17 years). Heart rate was 90 ± 15 bpm, systolic blood pressure 133 ± 19 mmHg and diastolic blood pressure 68 ± 15 mmHg. There was no statistical difference in the amplitude of harmonics between the invasive signal and Complior signal. When superimposing waveforms in the time domain, there was a small difference in the form factor (4.2 ± 2.8 %) and in the absolute area between the 2 waveforms (3.3 ± 1.7 mmHg·s(-1)). These differences were of the same magnitude as the beat-to-beat variation of the form factor (3.3 %) and of the absolute area (3.1 mmHg·s(-1)), respectively. The second systolic peak was detectable in 4 subjects, with no statistical difference between invasive and non-invasive values. The new pressure sensor of the Complior Analyse device recorded pressure waveforms accurately and could be used to perform pressure wave analysis.

Cytokine profiles in adults with imported malaria.

The increase in worldwide travel is making imported malaria a growing health concern in non-endemic countries. Most data on the pathophysiology of malaria come from endemic areas. Little is known about cytokine profiles during imported malaria. This study aimed at deciphering the relationship between cytokine host response and malaria severity among imported cases in France. This study reports cytokine profiles in adults with Plasmodium falciparum malaria included in the PALUREA prospective study conducted between 2006 and 2010. The patients were classified as having uncomplicated malaria (UM) or severe malaria (SM), with this last further categorized as very severe malaria (VSM) or less severe malaria (LSM). At hospital admission, eight blood cytokines were assayed in duplicate using Luminex® technology: interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-10, tumor necrosis factor (TNF)α, interferon (IFN)γ, and macrophage migration inhibitory factor (MIF). These assays were repeated on days 1 and 2 in the SM group. Of the 278 patients, 134 had UM and 144 SM. At hospital admission, over half the patients had undetectable levels of IL-1α, IL-1ß, IL-2, IL-4, IFNγ, and TNFα, while IL-10 and MIF were significantly higher in the SM vs. the UM group. Higher IL-10 was significantly associated with higher parasitemia (R = 0.32 [0.16-0.46]; P = 0.0001). In the SM group, IL-10 elevation persisting from admission to day 2 was significantly associated with subsequent nosocomial infection. Of eight tested cytokines, only MIF and IL-10 were associated with disease severity in adults with imported P. falciparum malaria. At admission, many patients had undetectable cytokine levels, suggesting that circulating cytokine assays may not be helpful as part of the routine evaluation of adults with imported malaria. Persisting high IL-10 concentration was associated with subsequent nosocomial infection, suggesting its possible interest in immune monitoring of most severe patients.

Epidemiology and outcome predictors in 450 patients with hanging-induced cardiac arrest: a retrospective study.

Background: Cardiac arrest is the most life-threatening complication of attempted suicide by hanging. However, data are scarce on its characteristics and outcome predictors. Methods: This retrospective observational multicentre study in 31 hospitals included consecutive adults admitted after cardiac arrest induced by suicidal hanging. Factors associated with in-hospital mortality were identified by multivariate logistic regression with multiple imputations for missing data and adjusted to the temporal trends over the study period. Results: Of 450 patients (350 men, median age, 43 [34-52] years), 305 (68%) had a psychiatric history, and 31 (6.9%) attempted hanging while hospitalized. The median time from unhanging to cardiopulmonary resuscitation was 0 [0-5] min, and the median time to return of spontaneous circulation (ROSC) was 20 [10-30] min. Seventy-nine (18%) patients survived to hospital discharge. Three variables were independently associated with higher in-hospital mortality: time from collapse or unhanging to ROSC>20 min (odds ratio [OR], 4.71; 95% confidence intervals [95%CIs], 2.02-10.96; p = 0.0004); glycaemia >1.4 g/L at admission (OR, 6.38; 95%CI, 2.60-15.66; p < 0.0001); and lactate >3.5 mmol/L at admission (OR, 6.08; 95%CI, 1.71-21.06; p = 0.005). A Glasgow Coma Scale (GCS) score of >5 at admission was associated with lower in-hospital mortality (OR, 0.009; 95%CI, 0.02-0.37; p = 0.0009). Conclusion: In patients with hanging-induced cardiac arrest, time from collapse or unhanging to return of spontaneous circulation, glycaemia, arterial lactate, and coma depth at admission were independently associated with survival to hospital discharge. Knowledge of these risk factors may help guide treatment decisions in these patients at high risk of hospital mortality.

Dynamic changes of pulse pressure but not of pulse pressure variation during passive leg raising predict preload responsiveness in critically ill patients with spontaneous breathing activity.

PURPOSE: To evaluate whether the changes in arterial pulse pressure (PP) and/or pulse pressure variation (PPV) during passive leg raising (PLR) can be used to evaluate preload responsiveness in patients with spontaneous breathing activity. MATERIALS AND METHODS: Patients ventilated with pressure support mode or totally spontaneously breathing were prospectively included. The values of PP and PPV were recorded before and at the end of PLR. The changes in cardiac index (CI) or the velocity-time integral (VTI) of the left ventricular outflow tract during PLR were tracked by the pulse contour analysis or transthoracic echocardiography. Patients exhibiting an increase in CI ≥ 10% or VTI ≥ 12% during PLR were defined as preload responders. RESULTS: Among 33 patients included, 28 (80%) received norepinephrine and 14 were preload responders. The increase in PP > 2 mmHg in absolute value (4% in percentage) during PLR (PLRPP) predicted preload responsiveness with an area under the receiver operating characteristic (AUROC) of 0.76 ± 0.09 (p = 0.003 vs. AUROC of 0.5). The changes in PPV during PLR, however, failed to predict preload responsiveness (p = 0.82 vs. AUROC of 0.5). CONCLUSION: In patients with full spontaneous breathing activity, PLR-induced changes in PP had a fair ability to assess preload responsiveness even when norepinephrine was administered. REGISTRATION NUMBER: ClinicalTrials.gov (NCT04369027).

Accuracy of clinicians' ability to predict the need for renal replacement therapy: a prospective multicenter study.

PURPOSE: Identifying patients who will receive renal replacement therapy (RRT) during intensive care unit (ICU) stay is a major challenge for intensivists. The objective of this study was to evaluate the performance of physicians in predicting the need for RRT at ICU admission and at acute kidney injury (AKI) diagnosis. METHODS: Prospective, multicenter study including all adult patients hospitalized in 16 ICUs in October 2020. Physician prediction was estimated at ICU admission and at AKI diagnosis, according to a visual Likert scale. Discrimination, risk stratification and benefit of physician estimation were assessed. Mixed logistic regression models of variables associated with risk of receiving RRT, with and without physician estimation, were compared. RESULTS: Six hundred and forty-nine patients were included, 270 (41.6%) developed AKI and 77 (11.8%) received RRT. At ICU admission and at AKI diagnosis, a model including physician prediction, the experience of the physician, SOFA score, serum creatinine and diuresis to determine need for RRT performed better than a model without physician estimation with an area under the ROC curve of 0.90 [95% CI 0.86-0.94, p < 0.008 (at ICU admission)] and 0.89 [95% CI 0.83-0.93, p = 0.0014 (at AKI diagnosis)]. In multivariate analysis, physician prediction was strongly associated with the need for RRT, independently of creatinine levels, diuresis, SOFA score and the experience of the doctor who made the prediction. CONCLUSION: As physicians are able to stratify patients at high risk of RRT, physician judgement should be taken into account when designing new randomized studies focusing on RRT initiation during AKI.

Immune-mediated thrombotic thrombocytopenic purpura prognosis is affected by blood pressure.

Background: The prevalence, prognostic role, and diagnostic value of blood pressure in immune-mediated thrombotic thrombocytopenic purpura (iTTP) and other thrombotic microangiopathies (TMAs) remain unclear. Methods: Using a national cohort of iTTP (n = 368), Shigatoxin-induced hemolytic uremic syndrome (n = 86), atypical hemolytic uremic syndrome (n = 84), and hypertension-related thrombotic microangiopathy (n = 25), we sought to compare the cohort's blood pressure profile to assess its impact on prognosis and diagnostic performances. Results: Patients with iTTP had lower blood pressure than patients with other TMAs, systolic (130 [interquartile range (IQR) 118-143] vs 161 [IQR 142-180] mmHg) and diastolic (76 [IQR 69-83] vs 92 [IQR 79-105] mmHg, both p < 0.001). The best threshold for iTTP diagnosis corresponded to a systolic blood pressure <150 mmHg. iTTP patients presenting with hypertension had a significantly poorer survival (hazard ratio 1.80, 95% confidence interval 1.07-3.04), and this effect remained significant after multivariable adjustment (hazard ratio = 1.14, 95% confidence interval 1.00-1.30). Addition of a blood pressure criterion modestly improved the French clinical score to predict a severe A disintegrin and metalloprotease with thrombospondin type 1 deficiency in patients with an intermediate score (i.e., either platelet count <30 × 109/L or serum creatinine <200 µM). Conclusions: Elevated blood pressure at admission affects the prognosis of iTTP patients and may help discriminate them from other TMA patients. Particular attention should be paid to blood pressure and its management in these patients.