Case Report: Co-infection with SARS-CoV-2 and influenza H1N1 in a patient with acute respiratory distress syndrome and a pulmonary sarcoidosis.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has been a global public health concern. Co-infection of SARS-CoV-2 and other respiratory syndrome has been rarely reported. We report coinfection of SARS-CoV-2 and 2009 H1N1 Influenza strain in a French patient with pneumonia leading to acute respiratory distress syndrome.  The patient also had a medical history of pulmonary sarcoidosis with a restrictive ventilatory syndrome, which would be a supplementary risk to develop a poor outcomes. This case highlights the possible coinfection of two severe SARS-CoV-2 and influenza H1N1 viruses, which presents a higher risk to extend the care duration. The overlapping clinical features of the two respiratory syndromes is a challenge, and awareness is required to recommend an early differential diagnosis.

Nephrotoxic drug burden among 1001 critically ill patients: impact on acute kidney injury.

BACKGROUND: Nephrotoxic drug prescription may contribute to acute kidney injury (AKI) occurrence and worsening among critically ill patients and thus to associated morbidity and mortality. The objectives of this study were to describe nephrotoxic drug prescription in a large intensive-care unit cohort and, through a case-control study nested in the prospective cohort, to evaluate the link of nephrotoxic prescription burden with AKI. RESULTS: Six hundred and seventeen patients (62%) received at least one nephrotoxic drug, among which 303 (30%) received two or more. AKI was observed in 609 patients (61%). A total of 351 patients were considered as cases developing or worsening AKI a given index day during the first week in the intensive-care unit. Three hundred and twenty-seven pairs of cases and controls (patients not developing or worsening AKI during the first week in the intensive-care unit, alive the case index day) matched on age, chronic kidney disease, and simplified acute physiology score 2 were analyzed. The nephrotoxic burden prior to the index day was measured in drug.days: each drug and each day of therapy increasing the burden by 1 drug.day. This represents a semi-quantitative evaluation of drug exposure, potentially easy to implement by clinicians. Nephrotoxic burden was significantly higher among cases than controls: odds ratio 1.20 and 95% confidence interval 1.04-1.38. Sensitivity analysis showed that this association between nephrotoxic drug prescription in the intensive-care unit and AKI was predominant among the patients with lower severity of disease (simplified acute physiology score 2 below 48). CONCLUSIONS: The frequently observed prescription of nephrotoxic drugs to critically ill patients may be evaluated semi-quantitatively through computing drug.day nephrotoxic burden, an index significantly associated with subsequent AKI occurrence, and worsening among patients with lower severity of disease.

Glomerular Hyper- and Hypofiltration During Acute Circulatory Failure: Iohexol-Based Gold-Standard Descriptive Study.

OBJECTIVE: To assess glomerular filtration rate in the early phase of acute circulatory failure by measuring iohexol plasma clearance. DESIGN: Interventional prospective multicentric study. SETTING: Three French ICUs in tertiary teaching hospitals. PATIENTS: Patients with acute circulatory failure within 12 hours after ICU admission. INTERVENTIONS: IV administration of a nontoxic 5-mL dose of iohexol. Collection of nine arterial blood samples over 24 hours for iohexol plasma concentration measurements. Iohexol clearance calculation with a population pharmacokinetic model. Iohexol clearance was an estimation of the mean glomerular filtration rate over 24 hours. MEASUREMENTS AND MAIN RESULTS: Among 99 included patients, we could calculate iohexol clearance for 85. The median iohexol clearance was 31 mL/min (interquartile range, 16-44). According to iohexol clearance, 41 patients (48%) had severe hypofiltration (clearance, < 30 mL/min), 29 (34%) had moderate hypofiltration, and 10 (12%) had mild hypofiltration (clearance, 30-60 and 60-90 mL/min, respectively). Four patients (5%) had normal glomerular filtration rate, and only one (1%) showed hyperfiltration (clearance, > 130 mL/min). Urinary creatinine clearance underestimated renal impairment in one patient out of two; the bias of iohexol clearance toward 24-hour urinary creatinine clearance over the same period was -18.1 mL/min (limits of agreement, -73.5 to 37.4). CONCLUSIONS: We demonstrated the feasibility of iohexol clearance measurement in unstable critically ill patients. Normal kidney function is exceptional during the early phase of acute circulatory failure. Glomerular filtration rate estimation by urinary creatinine clearance frequently fails to detect renal impairment. Hyperfiltration is very infrequent.

Effect of In-Bed Leg Cycling and Electrical Stimulation of the Quadriceps on Global Muscle Strength in Critically Ill Adults: A Randomized Clinical Trial.

Importance: Early in-bed cycling and electrical muscle stimulation may improve the benefits of rehabilitation in patients in the intensive care unit (ICU). Objective: To investigate whether early in-bed leg cycling plus electrical stimulation of the quadriceps muscles added to standardized early rehabilitation would result in greater muscle strength at discharge from the ICU. Design, Setting, and Participants: Single-center, randomized clinical trial enrolling critically ill adult patients at 1 ICU within an 1100-bed hospital in France. Enrollment lasted from July 2014 to June 2016 and there was a 6-month follow-up, which ended on November 24, 2016. Interventions: Patients were randomized to early in-bed leg cycling plus electrical stimulation of the quadriceps muscles added to standardized early rehabilitation (n = 159) or standardized early rehabilitation alone (usual care) (n = 155). Main Outcomes and Measures: The primary outcome was muscle strength at discharge from the ICU assessed by physiotherapists blinded to treatment group using the Medical Research Council grading system (score range, 0-60 points; a higher score reflects better muscle strength; minimal clinically important difference of 4 points). Secondary outcomes at ICU discharge included the number of ventilator-free days and ICU Mobility Scale score (range, 0-10; a higher score reflects better walking capability). Functional autonomy and health-related quality of life were assessed at 6 months. Results: Among 314 randomized patients, 312 (mean age, 66 years; women, 36%; receiving mechanical ventilation at study inclusion, 78%) completed the study and were included in the analysis. The median global Medical Research Council score at ICU discharge was 48 (interquartile range [IQR], 29 to 58) in the intervention group and 51 (IQR, 37 to 58) in the usual care group (median difference, -3.0 [95% CI, -7.0 to 2.8]; P = .28). The ICU Mobility Scale score at ICU discharge was 6 (IQR, 3 to 9) in both groups (median difference, 0 [95% CI, -1 to 2]; P = .52). The median number of ventilator-free days at day 28 was 21 (IQR, 6 to 25) in the intervention group and 22 (IQR, 10 to 25) in the usual care group (median difference, 1 [95% CI, -2 to 3]; P = .24). Clinically significant events occurred during mobilization sessions in 7 patients (4.4%) in the intervention group and in 9 patients (5.8%) in the usual care group. There were no significant between-group differences in the outcomes assessed at 6 months. Conclusions and Relevance: In this single-center randomized clinical trial involving patients admitted to the ICU, adding early in-bed leg cycling exercises and electrical stimulation of the quadriceps muscles to a standardized early rehabilitation program did not improve global muscle strength at discharge from the ICU. Trial Registration: ClinicalTrials.gov Identifier: NCT02185989.

Clinical relevance of pulse pressure variations for predicting fluid responsiveness in mechanically ventilated intensive care unit patients: the grey zone approach.

INTRODUCTION: Pulse pressure variation (PPV) has been shown to predict fluid responsiveness in ventilated intensive care unit (ICU) patients. The present study was aimed at assessing the diagnostic accuracy of PPV for prediction of fluid responsiveness by using the grey zone approach in a large population. METHODS: The study pooled data of 556 patients from nine French ICUs. Hemodynamic (PPV, central venous pressure (CVP) and cardiac output) and ventilator variables were recorded. Responders were defined as patients increasing their stroke volume more than or equal to 15% after fluid challenge. The receiver operating characteristic (ROC) curve and grey zone were defined for PPV. The grey zone was evaluated according to the risk of fluid infusion in hypoxemic patients. RESULTS: Fluid challenge led to increased stroke volume more than or equal to 15% in 267 patients (48%). The areas under the ROC curve of PPV and CVP were 0.73 (95% confidence interval (CI): 0.68 to 0.77) and 0.64 (95% CI 0.59 to 0.70), respectively (P<0.001). A grey zone of 4 to 17% (62% of patients) was found for PPV. A tidal volume more than or equal to 8 ml.kg(-1) and a driving pressure (plateau pressure - PEEP) more than 20 cmH2O significantly improved the area under the ROC curve for PPV. When taking into account the risk of fluid infusion, the grey zone for PPV was 2 to 13%. CONCLUSIONS: In ventilated ICU patients, PPV values between 4 and 17%, encountered in 62% patients exhibiting validity prerequisites, did not predict fluid responsiveness.

Are central venous lactate and arterial lactate interchangeable? A human retrospective study.

BACKGROUND: In critically ill patients, arterial blood lactate concentration (Lact(a)) and Lact(a) clearance are used for the diagnosis of shock, for prognosis assessment, and to guide therapy. In recent years, central venous oxygen saturation (ScvO(2)), a surrogate for mixed venous blood saturation, either measured by fiberoptic catheters or from central venous blood samples, was used in shock to estimate the global balance between oxygen delivery and consumption. When central venous blood is drawn for ScvO(2) measurement, it also could be used to measure central venous lactate concentration (Lact(cv)). In this study, we evaluated the utility of Lact(cv) and Lact(cv) clearance as predictors of Lact(a) and Lact(a) clearance, respectively, in critically ill patients. METHODS: This retrospective study was performed in an intensive care unit of a regional and teaching hospital. Using the electronic registry of our blood gas analyzer from March 2007 to December 2009, we identified patients with circulatory or respiratory failure who had pairs of Lact(cv) and Lact(a) obtained within a 30-minute interval. To assess the utility of Lact(cv) as a predictor of Lact(a) above 2 and 4 mmol/L, we calculated the area under receiver operating characteristic curves (AUCs) for these thresholds. We also calculated AUC of Lact(cv) clearance to detect a Lact(a) clearance <10% or >10%. RESULTS: Six hundred seventy-three Lact(cv)/Lact(a) pairs in 188 patients were analyzed. AUC of Lact(cv) to predict a Lact(a) above 2 and 4 mmol/L was 0.98 (95% confidence interval: 0.97-0.99) and 0.98 (95% confidence interval: 0.96-0.99), respectively. Lact(cv) with the cutoff value of 2 mmol/L can predict a Lact(a) above 2 mmol/L with sensitivity >92% and specificity >90%. AUC for Lact(cv) clearance to detect a Lact(a) clearance <10% or >10% was 0.93 or 0.94, respectively. CONCLUSION: Lact(cv) and Lact(a) collected within a 30-minute range are interchangeable for clinical practice.

Relation between mean arterial pressure and renal function in the early phase of shock: a prospective, explorative cohort study.

INTRODUCTION: Because of disturbed renal autoregulation, patients experiencing hypotension-induced renal insult might need higher levels of mean arterial pressure (MAP) than the 65 mmHg recommended level in order to avoid the progression of acute kidney insufficiency (AKI). METHODS: In 217 patients with sustained hypotension, enrolled and followed prospectively, we compared the evolution of the mean arterial pressure (MAP) during the first 24 hours between patients who will show AKI 72 hours after inclusion (AKIh72) and patients who will not. AKIh72 was defined as the need of renal replacement therapy or "Injury" or "Failure" classes of the 5-stage RIFLE classification (Risk, Injury, Failure, Loss of kidney function, End-stage renal disease) for acute kidney insufficiency using the creatinine and urine output criteria. This comparison was performed in four different subgroups of patients according to the presence or not of AKI at the sixth hour after inclusion (AKIh6 as defined as a serum creatinine level above 1.5 times baseline value within the first six hours) and the presence or not of septic shock at inclusion.The ability of MAP averaged over H6 to H24 to predict AKIh72 was assessed by the area under the receiver operating characteristic curve (AUC) and compared between groups. RESULTS: The MAP averaged over H6 to H24 or over H12 to H24 was significantly lower in patients who showed AKIh72 than in those who did not, only in septic shock patients with AKIh6, whereas no link was found between MAP and AKIh72 in the three others subgroups of patients. In patients with septic shock plus AKIh6, MAP averaged over H6 to H24 or over H12 to H24 had an AUC of 0.83 (0.72 to 0.92) or 0.84 (0.72 to 0.92), respectively, to predict AKIh72 . In these patients, the best level of MAP to prevent AKIh72 was between 72 and 82 mmHg. CONCLUSIONS: MAP about 72 to 82 mmHg could be necessary to avoid acute kidney insufficiency in patients with septic shock and initial renal function impairment.

Respiratory pulse pressure variation fails to predict fluid responsiveness in acute respiratory distress syndrome.

INTRODUCTION: Fluid responsiveness prediction is of utmost interest during acute respiratory distress syndrome (ARDS), but the performance of respiratory pulse pressure variation (ΔRESPPP) has scarcely been reported. In patients with ARDS, the pathophysiology of ΔRESPPP may differ from that of healthy lungs because of low tidal volume (Vt), high respiratory rate, decreased lung and sometimes chest wall compliance, which increase alveolar and/or pleural pressure. We aimed to assess ΔRESPPP in a large ARDS population. METHODS: Our study population of nonarrhythmic ARDS patients without inspiratory effort were considered responders if their cardiac output increased by >10% after 500-ml volume expansion. RESULTS: Among the 65 included patients (26 responders), the area under the receiver-operating curve (AUC) for ΔRESPPP was 0.75 (95% confidence interval (CI95): 0.62 to 0.85), and a best cutoff of 5% yielded positive and negative likelihood ratios of 4.8 (CI95: 3.6 to 6.2) and 0.32 (CI95: 0.1 to 0.8), respectively. Adjusting ΔRESPPP for Vt, airway driving pressure or respiratory variations in pulmonary artery occlusion pressure (ΔPAOP), a surrogate for pleural pressure variations, in 33 Swan-Ganz catheter carriers did not markedly improve its predictive performance. In patients with ΔPAOP above its median value (4 mmHg), AUC for ΔRESPPP was 1 (CI95: 0.73 to 1) as compared with 0.79 (CI95: 0.52 to 0.94) otherwise (P = 0.07). A 300-ml volume expansion induced a ≥ 2 mmHg increase of central venous pressure, suggesting a change in cardiac preload, in 40 patients, but none of the 28 of 40 nonresponders responded to an additional 200-ml volume expansion. CONCLUSIONS: During protective mechanical ventilation for early ARDS, partly because of insufficient changes in pleural pressure, ΔRESPPP performance was poor. Careful fluid challenges may be a safe alternative.

Central venous pressure measurements improve the accuracy of leg raising-induced change in pulse pressure to predict fluid responsiveness.

PURPOSE: Passive leg raising (PLR) is a maneuver performed to test the cardiac Frank-Starling mechanism. We assessed the influence of PLR-induced changes in preload on the performance of PLR-induced change in pulse pressure (Delta(PLR)PP) and cardiac output (Delta(PLR)CO) for fluid responsiveness prediction. METHODS: Sedated, nonarrhythmic patients with persistent shock were included in this prospective multicenter study. Cardiac output and pulse pressure were measured at baseline (patient supine), during PLR (lower limbs lifted to 45 degrees) and after 500-ml volume expansion. Patients were classified as responders or not. RESULTS: In the whole population (n = 102), the area under the receiver-operating characteristic curve (AUC) was 0.76 for Delta(PLR)PP and was higher for Delta(PLR)CO (0.89)(p < 0.05), but likelihood ratios were close to 1. In patients with a PLR-induced increase in central venous pressure (CVP) of at least 2 mmHg (n = 49), Delta(PLR)PP and Delta(PLR)CO disclosed higher AUCs than in the rest of the population (0.91 vs. 0.66 and 0.98 vs. 0.83; p < 0.05); positive/negative likelihood ratios were 9.3/0.14 (8% cutoff level) and 30/0.07 (7% cutoff level), respectively. CONCLUSIONS: A PLR-induced change in CVP > or =2 mmHg was required to allow clinical usefulness of PLR-derived indices. In this situation, Delta(PLR)PP performed well for predicting fluid responsiveness in deeply sedated patients.

Dopamine therapy in septic shock: detrimental effect on survival?

OBJECTIVE: The aim of this study is to examine the potential impact of dopamine therapy on 28-day mortality in adult septic shock. METHODS: For 66 months, clinical data, medications taken before admission, doses of catecholamines used, and biological parameters were recorded prospectively in all patients admitted for septic shock. This observational study was followed by (1) post hoc multivariate analyses and (2) risk-adjusted matched cohort study. MEASUREMENTS AND MAIN RESULTS: In 277 patients (65 +/- 14 years; Simplified Acute Physiology Score II = 54 +/- 19, 28-day mortality = 45%; hospital mortality = 53%), 6 factors were linked to 28-day mortality, including Simplified Acute Physiology Score II (P < .0001) and the use of dopamine (P = .043). In a pair-matched cohort of 132 patients, we observed a higher mortality with dopamine (28-day mortality of 62% vs 41%, respectively; P = .006). Dopamine remained linked to day 28 mortality by conditional logistic analysis (odds ratio = 6.2 [1.5-25]). A strong interaction between essential hypertension and dopamine was found, associated to 81% 28-day mortality in patients having both conditions. CONCLUSIONS: In our cohort study, dopamine use was linked to mortality as compared to other vasopressor therapies, particularly in patients with essential hypertension. Future randomized studies attempting to compare dopamine with other therapies in septic shock should pay attention to patients with essential hypertension.