Pierre-François Dequin

High versus Low Blood-Pressure Target in Patients with Septic Shock

BACKGROUND The Surviving Sepsis Campaign recommends targeting a mean arterial pressure of at least 65 mm Hg during initial resuscitation of patients with septic shock. However, whether this blood-pressure target is more or less effective than a higher target is unknown. METHODS In a multicenter, open-label trial, we randomly assigned 776 patients with septic shock to undergo resuscitation with a mean arterial pressure target of either 80 to 85 mm Hg (high-target group) or 65 to 70 mm Hg (low-target group). The primary end point was mortality at day 28. RESULTS At 28 days, there was no significant between-group difference in mortality, with deaths reported in 142 of 388 patients in the high-target group (36.6%) and 132 of 388 patients in the low-target group (34.0%) (hazard ratio in the high-target group, 1.07; 95% confidence interval [CI], 0.84 to 1.38; P=0.57). There was also no significant difference in mortality at 90 days, with 170 deaths (43.8%) and 164 deaths (42.3%), respectively (hazard ratio, 1.04; 95% CI, 0.83 to 1.30; P=0.74). The occurrence of serious adverse events did not differ significantly between the two groups (74 events [19.1%] and 69 events [17.8%], respectively; P=0.64). However, the incidence of newly diagnosed atrial fibrillation was higher in the high-target group than in the low-target group. Among patients with chronic hypertension, those in the high-target group required less renal-replacement therapy than did those in the low-target group, but such therapy was not associated with a difference in mortality. CONCLUSIONS Targeting a mean arterial pressure of 80 to 85 mm Hg, as compared with 65 to 70 mm Hg, in patients with septic shock undergoing resuscitation did not result in significant differences in mortality at either 28 or 90 days. (Funded by the French Ministry of Health; SEPSISPAM ClinicalTrials.gov number, NCT01149278.).

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

IntroductionFluid 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.MethodsOur study population of nonarrhythmic ARDS patients without inspiratory effort were considered responders if their cardiac output increased by >10% after 500-ml volume expansion.ResultsAmong 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.ConclusionsDuring 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.

Prognosis and 1-year mortality of intensive care unit patients with severe hepatic encephalopathy ☆

PURPOSE Data regarding outcome of patients with chronic liver disease with severe hepatic encephalopathy in intensive care unit are currently scarce. METHODS This study is a retrospective observational case series in a medical intensive care unit (ICU) in a university hospital from 1995 to 2005. Patients with hepatic encephalopathy (HE) (admitted with or developing) were identified. Clinical and laboratory parameters were analyzed to determinate predictors of ICU and 1-year mortality. RESULTS Seventy-one patients were included (53 male). Median Simplified Acute Physiology Score was 56 with Child-Pugh score 11 +/- 2. Seventy-six percent of patients were admitted with coma (Glasgow Coma Scale, 7.7 +/- 4). Eighty-two percent of patients required intubation, and 28% vasopressors. Thirty-five percent died during ICU stay. At 1 year, mortality was 54%. Univariate analysis identified arterial hypotension, mechanical ventilation, vasopressors at any time, acute renal failure, Simplified Acute Physiology Score, and sepsis associated with ICU mortality. In multivariate analysis, vasopressor use or acute renal failure was the main independent predictor of ICU death and 1-year mortality. Patients free of these risk factors, even requiring intubation, were identified as isolated HE, with lower mortality rates. CONCLUSION Predictors of outcome were similar to other groups of patients with liver disease admitted for other reasons. Intensive care unit mortality was lower than reported for other groups of patients with similar illness. Patients with severe HE admitted to ICU with no organ dysfunction other than mechanical ventilation had a better outcome and may require ICU admission.

Outcome of older patients requiring ventilatory support in intensive care: impact of nutritional status.

OBJECTIVES: To determine predictors of mortality in the intensive care unit (ICU) and at 6 months after discharge; to assess the lifestyles of survivors 6 months after discharge.

Tracking Hypotension and Dynamic Changes in Arterial Blood Pressure with Brachial Cuff Measurements

BACKGROUND: Arterial cannulation is strongly recommended during shock. Nevertheless, this procedure is associated with significant risks and may delay other emergent procedures. We assessed the discriminative power of brachial cuff oscillometric noninvasive blood pressure (NIBP) for identifying patients with an invasive mean arterial blood pressure (MAP) below 65 mm Hg or increasing their invasive MAP after cardiovascular interventions. METHODS: This prospective study, conducted in three intensive care units, included adults in circulatory failure who underwent 45° passive leg raising, 300 mL fluid loading, and additional 200 mL fluid loading. The collected data were four invasive and noninvasive MAP measurements at each study phase. RESULTS: Among 111 patients (50 septic, 15 cardiogenic, and 46 other source of shock), when averaging measurements of each study phase, NIBP measurements accurately predicted an invasive MAP lower than 65 mm Hg: area under the receiver operating characteristic curve 0.90 (95% CI: 0.71–1), positive and negative likelihood ratios 7.7 (95% CI: 5.4–11) and 0.31 (95% CI: 0.22–0.44) (cutoff 65 mm Hg). For identifying patients increasing their invasive MAP by more than 10%, the area under the receiver operating characteristic curve was 0.95 (95% CI: 0.92–0.96); positive and negative likelihood ratios (cutoff 10%) were 25.7 (95% CI: 10.8–61.4) and 0.26 (95% CI: 0.2–0.34). CONCLUSIONS: NIBP measurements have a good discriminative power for identifying hypotensive patients and performed even better in tracking MAP changes, provided that one averages four NIBP measurements.

Population pharmacokinetics of ceftriaxone in critically ill septic patients: a reappraisal

AIMS To investigate the population pharmacokinetics of ceftriaxone in critically ill patients suffering from sepsis, severe sepsis or septic shock. METHODS Blood samples were collected at preselected times in 54 adult patients suffering from sepsis, severe sepsis or septic shock in order to determine ceftriaxone concentrations using high-performance liquid chromatography-ultraviolet detection. The pharmacokinetics of ceftriaxone were assessed on two separate occasions for each patient: on the second day of ceftriaxone therapy and 48 h after catecholamine withdrawal in patients with septic shock, or on the fifth day in patients with sepsis. The population pharmacokinetics of ceftriaxone were studied using nonlinear mixed effects modelling. RESULTS The population estimates (interindividual variability; coefficient of variation) for ceftriaxone pharmacokinetics were: a clearance of 0.88 l h(-1) (49%), a mean half-life of 9.6 h (range 0.83-28.6 h) and a total volume of distribution of 19.5 l (range 6.48-35.2 l). The total volume of distribution was higher than that generally found in healthy individuals and increased with the severity of sepsis. However, the only covariate influencing the ceftriaxone pharmacokinetics was creatinine clearance. Dosage simulations showed that the risk of ceftriaxone concentrations dropping below the minimum inhibitory concentration threshold was low. CONCLUSIONS Despite the wide interpatient variability of ceftriaxone pharmacokinetic parameters, our results revealed that increasing the ceftriaxone dosage when treating critically ill patients is unnecessary. The risk of ceftriaxone concentrations dropping below the minimum inhibitory concentration threshold is limited to patients with high glomerular filtration rates or infections with high minimum inhibitory concentration pathogens (>1 mg l(-1)).

Feasibility of Right Ventricular Longitudinal Systolic Function Evaluation with Transthoracic Echocardiographic Indices Derived from Tricuspid Annular Motion: A Preliminary Study in Acute Respiratory Distress Syndrome

Introduction: Assessment of right ventricular (RV) function in patients with acute respiratory distress syndrome (ARDS) remains challenging. Transthoracic echocardiographic (TTE) indices based on longitudinal systolic RV function are now considered as a reliable evaluation of RV function. We investigated feasibility of two methods in ARDS patients. Methods: Prospective observational study. TTE was performed after 12–36 hours of mechanical ventilation. Feasibility of tricuspid annular motion (St), tricuspid annular plane systolic excursion (TAPSE) was compared to usual two‐dimensional (2D) study: fractional area change (RVFAC) and ratio of right to left ventricular end‐diastolic area (RVEDA/LVEDA). Results: Fifty patients were investigated, with TTE possible in all but two patients. Feasibility was 62% for RVFAC, 72% for RVEDA/LVEDA, and 96% for TAPSE and St. RV dilatation (RVEDA/LVEDA ≥0.60) was found in 16 patients, including 4 patients with acute cor pulmonale. A longitudinal RV dysfunction (TAPSE < 12 mm or St < 11.5 cm/sec) was suspected in 30% of patients. Relation between both longitudinal indices was modest (r2= 0.36, P < 0.001). TAPSE (but not St) was found poorly related to RVFAC (r2= 0.27, P = 0.03). Both indices were related to LV function (St: r2= 0.27, TAPSE: r2= 0.17, both P < 0.05). Conclusion: Despite a superior feasibility than 2D study, our results suggest that both indices may not bring identical information to echo study. TAPSE may be more adapted to ICU use than St. Both should be further investigated in terms of analysis of RV function and ventricular interdependence. Their relations with LV function may limit their use as sole markers of RV function in this population. (Echocardiography 2012;29:513‐521)

Cardiopulmonary resuscitation in the prone position: Kouwenhoven revisited

Sir: It has been proposed that severely hypoxemic patients be ventilated in the prone position, in an attempt to improve gas exchange [1]. Testing this position in patients with the acute respiratory distress syndrome (ARDS) is recommended [21. However, no guidelines are available for cases of life-threatening events occurring with the patient in the prone position especially cardiac arrest. We report a case of successful cardiopulmonary resuscitation of a patient ventilated in the prone position, without changing the patients position. A 48-year-old man was being ventilated for community-acquired pneumonia. His gas exchange (partial pressure of oxygen in arterial blood 4.3 kPa and of carbon dioxide 16.4 kPa and pH 7.14) deteriorated despite controlmode ventilation with 10 cmH20 positive end-expiratory pressure, 100 p. 100 fractional inspired oxygen, and 20 ppm inhaled nitric oxide. He was then turned to the prone position. A few minutes later, asytole developed and blood pressure became unobtainable. Cardiac massage was begun immediately with the patient in the prone position. One physician placed the flat of one hand under the patients sternum, while another physician compressed the mid-thoracic spine rhythmically with both hands (Fig. 1). Arterial radial blood pressure was maintained at least at 80/35 mmHg throughout resuscitation. Epinephrine (1 mg i.v.) was injected twice at a 3-min interval. Five minutes after starting cardiac compression, sinus rhythm resumed and blood pressure was maintained at 140/85 mmHg. Gas exchange dramatically improved a few hours later. Seven days after the incident, the patient was awake and well oriented. The conventional approach of closed chest compression is well established with the patient in the supine position [3]. However, cardiac massage might be required for patients in the prone position, e.g., during anesthesia for spinal or posterior fossa surgery. Three cases of successful resuscitation have been reported in these circumstances [4, 5] in which resuming the supine position might have injured the brain or spinal cord. Changing the position has some other drawbacks for ARDS patients ventilated in the prone position: (a) it is time consuming and delays initiation of cardiac massage; (b) moving the patient into the supine position without proper protection may induce certain complications, e.g., accidental extubation, dislodging the venous catheter, or shoulder injury to the patient; (c) turning a patient from one position into another requires at least four members of staff, who are not always immediately available in emergency situations. For these reasons, we suggest trying the

Right-to-left interatrial shunt in ARDS: dramatic improvement in prone position

Abstract The mechanisms leading to shunting through a patent foramen ovale include high right-sided cardiac pressures and respiratory factors due to mechanical ventilation and also anatomical changes in the right atrium as described in the platypnea-orthodeoxia syndrome. We report a patient with the adult respiratory distress syndrome (ARDS) who had a right-to-left atrial shunt which decreased in the prone position, after which oxygenation improved. The patient was admitted to the intensive care unit because of ARDS due to an invasive fungal infection. He had a history of chronic lymphocytic leukemia and paradoxical embolisms through a patent foramen ovale. Despite mechanical ventilation and antifungal treatment he developed severe ARDS. He was therefore turned to the prone position. Blood gas values improved dramatically (arterial oxygen tension/fractional inspired oxygen ratio increasing from 59 to 278 torr). Transcranial Doppler sonography was performed with bubble study, which confirmed a massive right-to-left shunt in the supine position and which instantaneously decreased in the prone position. This case suggests that a decrease in right-to-left shunt in patients who have a patent foramen ovale could partly explain the improvement in hypoxemia in the prone position.

Severe and multiple hypoglycemic episodes are associated with increased risk of death in ICU patients

IntroductionIn a randomized controlled trial comparing tight glucose control with a computerized decision support system and conventional protocols (post hoc analysis), we tested the hypothesis that hypoglycemia is associated with a poor outcome, even when controlling for initial severity.MethodsWe looked for moderate (2.2 to 3.3 mmol/L) and severe (<2.2 mmol/L) hypoglycemia, multiple hypoglycemic events (n ≥3) and the other main components of glycemic control (mean blood glucose level and blood glucose coefficient of variation (CV)). The primary endpoint was 90-day mortality. We used both a multivariable analysis taking into account only variables observed at admission and a multivariable matching process (greedy matching algorithm; caliper width of 10−5 digit with no replacement).ResultsA total of 2,601 patients were analyzed and divided into three groups: no hypoglycemia (n =1,474), moderate hypoglycemia (n =874, 34%) and severe hypoglycemia (n =253, 10%). Patients with moderate or severe hypoglycemia had a poorer prognosis, as shown by a higher mortality rate (36% and 54%, respectively, vs. 28%) and decreased number of treatment-free days. In the multivariable analysis, severe (odds ratio (OR), 1.50; 95% CI, 1.36 to 1.56; P =0.043) and multiple hypoglycemic events (OR, 1.76, 95% CI, 1.31 to 3.37; P <0.001) were significantly associated with mortality, whereas blood glucose CV was not. Using multivariable matching, patients with severe (53% vs. 35%; P <0.001), moderate (33% vs. 27%; P =0.029) and multiple hypoglycemic events (46% vs. 32%, P <0.001) had a higher 90-day mortality.ConclusionIn a large cohort of ICU patients, severe hypoglycemia and multiple hypoglycemic events were associated with increased 90-day mortality.Trial registrationClinicaltrials.gov Identifier: NCT01002482. Registered 26 October 2009.