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.

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.

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).

Carboplatin: a new cause of severe type B lactic acidosis secondary to mitochondrial DNA damage.

In adults, type B lactic acidosis is rare and generally associated with a toxin, particularly metformin or antiretroviral nucleosides analogues. We report a case of lactic acidosis caused by carboplatin in a 50-year-old woman suffering from primary peritoneal carcinoma. She was admitted for severe lactic acidosis (pH 6.77, lactate 19 mmol/L) associated with multiple organ failure (PaO2/FiO2 96, creatinine 231 µmol/L, aspartate aminotransferase > 25,000 UI, factor V 13%) occurring during the sixth carboplatin cycle. In the absence of sepsis, internal bleeding, alcohol poisoning, or other causes of lactic acidosis, the hypothesis of mitochondrial DNA (mtDNA) damage secondary to carboplatin and subsequent mitochondrial dysfunction leading to increase in glycolysis and lactic acidosis was suspected. L-Carnitine therapy associated with aggressive intensive care support led to a progressive improvement (pH 7.29, bicarbonate 24 mmol/L, lactate 7.8 mmol/L), but life support was withdrawn on day 7 because of peritoneal relapse. A respiratory chain dysfunction of enzyme activities encoded by mtDNA and multiple mtDNA deletions were found in muscle and liver tissue. It is generally accepted that carboplatin toxicity results in bone marrow suppression, renal dysfunction, or neurotoxicity and that platinating agents have no direct mitochondrial effect. However, although very unusual, emergency physicians must be aware that carboplatin can cause mitochondrial toxicity and trigger lactic acidosis.

Are bedside colonoscopies performed in intensive care unit really useful?

PURPOSE: Effectiveness of bedside Colonoscopies in Intensive Care Unit (CICU) might be limited by the poor quality of colonic preparation, and their feasibility. We sought to describe the indications and the profitability of CICU. METHODS: Retrospective, bicenter observational study (2004-2015) in unselected critically ill patients. We questioned the clinical profitability of CICU, according to its indications and preparation. RESULTS: One hundred and eleven CICU were performed in 84 patients (sex ratio 1.4, 49 M/35F; age 72.9 years [61.7-84.7]), for lower gastro-intestinal bleeding in 67 patients (LGIB, 60.3%) and for other causes in 44 (39.6%). The profitability was more frequent when CICU was performed for another reason than LGIB (75% vs 28.3%; p < 0.0001). Preparation was good in 47 procedures (42.3%) and allowed 33 complete CICU (29.7%). Fifty-six CICU (50.4%) were performed as a 2nd investigation after a contrast enhanced computed tomography. Three CICU were complicated by 3 hemodynamic and 2 respiratory failures, but none of them were fatal. CONCLUSIONS: CICU is clinically useful in half of cases, in the diagnostic and the therapeutic management of critically ill patients. Its profitability is close to scheduled colonoscopies and superior in non-lower gastro-intestinal bleeding indications.

Effect of Noninvasive Ventilation After Unplanned Extubation.

BACKGROUND: Our study set out to test the effect of noninvasive ventilation (NIV) performed after unplanned extubation. METHODS: Retrospective analysis of prospectively collected data in a university-affiliated mixed ICU of 12 beds during a 5-y period (January 2013 to December 2017). Unplanned extubation was defined as the occurrence of an unplanned removal of the endotracheal tube, whether deliberate or accidental. NIV after an unplanned extubation was not protocolized and was decided by the physician in charge on an individual basis. RESULTS: A total of 121 subjects (median [25th-75th percentile] age, 62.1 [43.3-73.6] y; median [25th-75th percentile] Simplified Acute Physiology Score II, 45 [36-54]) experienced 131 unplanned extubation episodes. Re-intubation was deemed necessary in 35 subjects (28.9%). NIV was used in 24 subjects (19.8%) (prophylactic NIV, n = 10; rescue NIV, n = 14). The re-intubation rates were 25.8%, 10%, and 64.3% in the no NIV, prophylactic, and rescue NIV subgroups, respectively. The median (25th-75th percentile) time to re-intubation was longer for subjects on NIV (9.1 [3.5-49.2] vs 0.46 [0.25-1] h, P = .001). The median (25th-75th percentile) ICU length of stay and duration of mechanical ventilation were longer in the subjects who underwent NIV (14.5 [7-24.5] vs 6 [3-14] d, respectively, P = .004; and 9 [3-22] vs 3 [1-7.3] d, respectively, P = .003). CONCLUSIONS: NIV after unplanned extubation had uncertain efficacy, especially when provided as rescue management of postextubation respiratory failure.

Constipation in critical care patients: both timing and duration matter.

OBJECTIVE: Most of the studies have defined constipation as a period without stool after ICU admission. We aimed to test the impact of both duration and timing of infrequent defecation in critical care patients. PATIENTS AND METHODS: We performed a prospective, bi-center, observational study. Patients were divided into three subgroups: 'not constipated', '3-5 days', and 'at least 6 days' (longest period without stool passage, respectively, shorter than 3 days, 3-5 days, and ≥6 days). Furthermore, 'early' constipated patients were defined as those for whom the longest time to stool passage occurred just after ICU admission, whereas for 'late' constipated patients the longest period without stool occurred later during ICU stay. RESULTS: A total of 182 patients were included: the mean age was 67.2 years (54.4-78.9 years), 80 were women, and simplified acute physiology score II was 42 (34-52). In all, 42 (23.1%), 82 (45.1%), and 58 (31.8%) belonged to the nonconstipated, 3-5 days, or greater than or equal to 6 days subgroup of patients, respectively. Time spent under mechanical ventilation and ICU length of stay was longer in the greater than or equal to 6 days subgroups as compared with both other subgroups. ICU stay was longer in the 3-5 days subgroup as compared with the not constipated patients. Furthermore, the late patients of the greater than or equal to 6 days subgroups exhibited worse survival as compared with all other patients. CONCLUSION: Both timing and duration of infrequent defecation seem to have an impact on critical care patient's outcome, and should therefore be included in the diagnostic criteria.

Comments to: Risk factors for late defecation and its association with the outcomes of critically ill patients: a retrospective observational study.

In a previous retrospective work, it has been postulated that early enteral nutrition was a protective factor against late defecation and its subsequent consequences in critically ill patients. We raise concerns about methodological issues limiting the conclusions.

Erratum to: Comments to: Risk factors for late defecation and its association with the outcomes of critically ill patients: a retrospective observational study.

[This corrects the article DOI: 10.1186/s40560-016-0170-3.].

Constipation incidence and impact in medical critical care patients: importance of the definition criterion.

BACKGROUND: Constipation incidence and impact remain controversial in the ICU. This may depend on the definition criterion used in the previous studies on the field. We aimed to determine the frequency and significance of constipation according to its definition criterion. METHODS: This is a prospective observational study. Adult patients without a cause of transit time modification and laxative intake within the first 3 days were screened. Constipation was defined by a first stool passage occurring after 3 days of ICU stay. Thereafter, we identified two subgroups of patients: absence of stool passage more than 3 days but less than 6 days (3-day subgroup), and no stool passage for 6 days or more (6-day subgroup). Survival, length of stay and time spent under mechanical ventilation (MV) were compared according to constipation status. RESULTS: Among 189 included patients [age 60.8 (49.5-74.2) years, SAPS II 44 (34-53)], 98 (51.9%) exhibited constipation (3-day subgroup n=53, 6-day subgroup n=45). Constipated patients were more likely to receive MV, sedation, vasopressors, enteral nutrition and neuromuscular blocking agents. ICU length of stay and time spent under MV was longer in the 6-day subgroup but not in the 3-day subgroup of patients. CONCLUSION: With regard to outcomes, defining constipation by the absence of stool passage less than 6 days after ICU admission does not identify a specific subset of population. Further studies on the management of this condition should focus on these 'long-term' constipated patients.

Accuracy of clinical presentation for differentiating bacterial from viral meningitis in adults: a multivariate approach.

OBJECTIVE: To determine whether bacterial (BM) and viral (VM) meningitis can be differentiated based on initial clinical presentation. DESIGN AND SETTING: Retrospective cohort study in a medical emergency department and intensive care unit in a university hospital. PATIENTS: 144 adults, including 90 with confirmed BM and 54 unpretreated VM. MEASUREMENTS AND RESULTS: Symptoms, examination findings, paraclinical data, and clinical outcome were assessed. Severity was defined by the presence at referral of one of the following criteria: altered consciousness, seizures, focal neurological findings, and shock. After univariate analyses we performed stepwise logistic regression to determine predictors for BM available at referral (except for CSF Gram stain) and logistic regression using previously validated CSF cutoffs. Univariate methods identified the presence of one sign of severity as the most important predictor for BM (sensitivity 0.989, specificity 0.981, positive predictive value 0.989, negative predictive value 0.981, odds ratio 4,770) and showed that CSF results differ in BM and in VM (except for CSF glucose). Logistic regression analysis revealed severity and CSF absolute neutrophil count as the two predictors of BM (R2=0.876). Logistic analysis showed that BM was related to severity (beta=6.46+/-1.27) and a CSF absolute neutrophil count above 1,000/mm3 whereas CSF glucose below 2 mmol/l and CSF protein higher than 2 g/l were not predictive. CONCLUSIONS: The presence of at least one sign of severity at referral and a CSF absolute neutrophil count above 1,000/mm3 mm are predictive of BM.

Handgrip Strength Predicts Difficult Weaning But Not Extubation Failure in Mechanically Ventilated Subjects.

BACKGROUND: Muscle weakness, defined by the Medical Research Council scale, has been associated with delay in mechanical ventilation weaning. In this study, we evaluated handgrip strength as a prediction tool in weaning outcome. METHODS: This was a 1-y prospective study in 2 ICUs in 2 university hospitals. Adult patients who were on mechanical ventilation for at least 48 h and eligible for mechanical ventilation weaning were screened for inclusion. Handgrip strength was evaluated using a handheld dynamometer before each spontaneous breathing trial (SBT). Attending physicians were unaware of handgrip strength and decided on extubation according to guidelines. RESULTS: Eighty-four subjects were included (median age 66 [53-79] y, with a median Simplified Acute Physiology Score II of 49 [37-63]). At the first evaluation, median handgrip strength was significantly associated with weaning outcome as defined by international guidelines: simple (20 [12-26] kg), difficult (12 [6-21] kg), or prolonged (6 [3-11] kg) weaning (P = .008). Time to liberation from mechanical ventilation and ICU stay were significantly longer for subjects classified as having muscle weakness according to the handgrip strength-derived definition (P = .02 and P = .03, respectively). In multivariate analysis, known history of COPD (odds ratio [OR] 5.48, 95% CI 1.44-20.86, P = .01), sex (OR 6.16, 95% CI 1.64-23.16, P = .007), and handgrip strength at the first SBT (OR 0.89, 95% CI 0.85-0.97, P = .004) were significantly associated with difficult or prolonged weaning. Extubation failure, as defined by re-intubation or unscheduled noninvasive ventilation within 48 h after extubation, occurred 14 times after 92 attempts, leading to an extubation failure rate of 15%. No association was found between handgrip strength and extubation outcome. CONCLUSIONS: Muscle weakness, assessed by handgrip strength, is associated with difficult or prolonged mechanical ventilation weaning and ICU stay, but not with extubation outcome.