Prognostic significance of central venous-to-arterial carbon dioxide difference during the first 24 hours of septic shock in patients with and without impaired cardiac function.

OBJECTIVE: To investigate the prognostic significance of central venous-to-arterial carbon dioxide difference (cv-art CO 2 gap) during septic shock in patients with and without impaired cardiac function. METHODS: We performed a prospective cohort study in 10 French intensive care units. Patients suffering from septic shock were assigned to the impaired cardiac function group ('cardiac group', n =123) if they had atrial fibrillation (AF) and/or left ventricular ejection fraction (LVEF) <50% at study entry and to the non-cardiac group ( n =240) otherwise. RESULTS: Central venous and arterial blood gases were sampled every 6 h during the first 24 h to calculate cv-art CO 2 gap. Patients in the cardiac group had a higher cv-art CO 2 gap [at study entry and 6 and 12 h (all P <0.02)] than the non-cardiac group. Patients in the cardiac group with a cv-art CO 2 gap >0.9 kPa at 12 h had a higher risk of day 28 mortality (hazard ratio=3.18; P =0.0049). Among the 59 patients in the cardiac group with mean arterial pressure (MAP) ≥65 mm Hg, central venous pressure (CVP) ≥8 mm Hg and central venous oxygen saturation (ScvO 2 ) ≥70% at 12 h, those with a high cv-art CO 2 gap (>0.9 kPa; n =19) had a higher day 28 mortality (37% vs. 13%; P =0.042). In the non-cardiac group, a high cv-art CO 2 gap was not linked to a higher risk of day 28 death, whatever the threshold value of the cv-art CO 2 gap. CONCLUSION: Patients with septic shock and with AF and/or low LVEF were more prone to a persistent high cv-art CO 2 gap, even when initial resuscitation succeeded in normalizing MAP, CVP, and ScvO 2 . In these patients, a persistent high cv-art CO 2 gap at 12 h was significantly associated with higher day 28 mortality.

Evaluation of a flexible bronchoscope prototype designed for bronchoscopy during mechanical ventilation: a proof-of-concept study.

Bronchoscopy during mechanical ventilation of patients' lungs significantly affects ventilation because of partial obstruction of the tracheal tube, and may thus be omitted in the most severely ill patients. It has not previously been possible to reduce the external diameter of the bronchoscope without reducing the diameter of the suction channel, thus reducing the suctioning capacity of the device. We believed that a better-designed bronchoscope could improve the safety of bronchoscopy in patients whose lungs were ventilated. We designed a flexible bronchoscope prototype with a drumstick-shaped head consisting of a long, thin proximal portion; a short and large distal portion for camera docking; and a large suction channel throughout the length of the device. The aims of our study were to test the impact of our prototype on mechanical ventilation when inserted into the tracheal tube, and to assess suctioning capacity. We first tested the efficiency of the suction channel, and demonstrated that the suction flow of the prototype was similar to that of conventional adult bronchoscopes. We next evaluated the consequences of bronchoscopy when using the prototype on minute ventilation and intrathoracic pressures during mechanical ventilation: firstly, in vitro using a breathing simulator; and secondly, in vivo using a porcine model of pulmonary ventilation. The insertion of adult bronchoscopes into the tracheal tube immediately impaired the protective ventilation strategy employed, whereas the prototype preserved it. For the first time, we have developed an innovative flexible bronchoscope designed for bronchoscopy during invasive mechanical ventilation, that both preserved the protective ventilation strategy, and enabled efficient suction flow.

Predicting arterial blood gas and lactate from central venous blood analysis in critically ill patients: a multicentre, prospective, diagnostic accuracy study.

BACKGROUND: The estimation of arterial blood gas and lactate from central venous blood analysis and pulse oximetry [Formula: see text] readings has not yet been extensively validated. METHODS: In this multicentre, prospective study performed in 590 patients with acute circulatory failure, we measured blood gases and lactate in simultaneous central venous and arterial blood samples at 6 h intervals during the first 24 h after insertion of central venous and arterial catheters. The study population was randomly divided in a 2:1 ratio into model derivation and validation sets. We derived predictive models of arterial pH, carbon dioxide partial pressure, oxygen saturation, and lactate, using clinical characteristics, [Formula: see text], and central venous blood gas values as predictors, and then tested their performance in the validation set. RESULTS: In the validation set, the agreement intervals between predicted and actual values were -0.078/+0.084 units for arterial pH, -1.32/+1.36 kPa for arterial carbon dioxide partial pressure, -5.15/+4.47% for arterial oxygen saturation, and -1.07/+1.05 mmol litre(-1) for arterial lactate (i.e. around two times our predefined clinically tolerable intervals for all variables). This led to ∼5% (or less) of extreme-to-extreme misclassifications, thus giving our predictive models only marginal agreement. Thresholds of predicted variables (as determined from the derivation set) showed high predictive values (consistently >94%), to exclude abnormal arterial values in the validation set. CONCLUSIONS: Using clinical characteristics, [Formula: see text], and central venous blood analysis, we predicted arterial blood gas and lactate values with marginal accuracy in patients with circulatory failure. Further studies are required to establish whether the developed models can be used with acceptable safety.

Pharmacokinetics of high-dose nebulized amikacin in ventilated critically ill patients.

BACKGROUND: Antibiotic nebulization theoretically allows the delivery of high doses to the lungs together with limited systemic exposure and toxicity. This study aimed to describe amikacin pharmacokinetics, and especially its absorption, in patients treated with high-dose nebulized amikacin. PATIENTS AND METHODS: Twenty critically ill patients experiencing ventilator-associated pneumonia received a 20 mg/kg infusion of amikacin, followed by either three other infusions or three nebulizations of 60 mg/kg amikacin. An extensive sampling regimen allowed measurement of amikacin serum concentrations at 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 24 h after each administration. Amikacin pharmacokinetics was studied by population compartmental modelling. RESULTS: Amikacin pharmacokinetics was best described using a two-compartment structural model with first-order distribution and elimination, in which lung absorption was described using a transit model. Estimated means (interindividual variability) of the main parameters were: bioavailability F = 2.65% (22.1%); transit compartments n = 1.58 (fixed); transit constant ktr = 1.38 h-1 (33.4%); central volume Vc = 10.2 L (10.5%); and elimination constant k10 = 0.488 h-1 (35.8%). The addition of interoccasion variability on F (44.0%) and k10 (41.7%) allowed the description of intraindividual variability of bioavailability and elimination. Amikacin clearance was positively correlated with baseline creatinine clearance. CONCLUSIONS: Our pharmacokinetic model provided an accurate description of amikacin concentrations following nebulization. There was wide interindividual and interoccasion variability in the absorption and elimination of amikacin. Nevertheless, systemic exposure after nebulization was always much lower than after infusion, an observation suggesting that nebulized high doses are safe in this regard and may be used to treat ventilator-associated pneumonia.

The effect of fibreoptic bronchoscopy in acute respiratory distress syndrome: experimental evidence from a lung model.

Flexible bronchoscopy is essential for appropriate care during mechanical ventilation, but can significantly affect mechanical ventilation of the lungs, particularly for patients with acute respiratory distress syndrome. We aimed to describe the consequences of bronchoscopy during lung-protective ventilation in a bench study, and thereby to determine the optimal diameter of the bronchoscope for avoiding disruption of the protective-ventilation strategy during the procedure. Immediately following the insertion of the bronchoscope into the tracheal tube, either minute ventilation decreased significantly, or positive end-expiratory pressure increased substantially, according to the setting of the inspiratory pressure limit. The increase in end-expiratory pressure led to an equivalent increase in the plateau pressure, and lung-protective ventilation was significantly altered during the procedure. We showed that a bronchoscope with an external diameter of 4 mm (or less) would allow safer bronchoscopic interventions in patients with severe acute respiratory distress syndrome.

An evaluation of a new single-use flexible bronchoscope with a large suction channel: reliability of bronchoalveolar lavage in ventilated piglets and initial clinical experience.

A single-use flexible bronchoscope with a large suction channel has become available recently and we have evaluated this innovative device. Firstly, bronchoalveolar lavage was performed and quantified in ventilated piglets. Next, the bronchoscope was evaluated in three intensive care units and a satisfaction questionnaire was carried out. Sixteen bronchoalveolar lavages were performed in piglets with a recovery rate of 83 (79-86 [72-89])% of the instilled volume. Quality and performance of all devices tested was identical. The medical satisfaction questionnaire was as follows: 'acceptable' to 'very good' for quality of aspiration, manoeuvrability and quality of vision; 'very good' to 'perfect' for setting up and insertion. This encouraging preliminary evaluation demonstrates the effectiveness of this new single-use device, which may obviate the need for disinfection procedures and, thereby, eradicate a potential vector of patient cross-contamination.

Hashimoto's encephalopathy in the intensive care unit.

BACKGROUND: Since the first description of Hashimoto's Encephalitis (HE) in 1966 by Lord Brain, the number of reported cases has continued to increase. In addition, cases of status epilepticus have been reported, suggesting a role for intensive care unit (ICU) practitioners in taking care of patients with HE. METHODS: A retrospective cohort study in ICU patients with HE was performed at the University Hospital of Tours, France. RESULTS: Eight HE cases were admitted to the ICU between 1/1/2000 and 1/1/2012. Herein, we describe the characteristics of the patients, with an emphasis on ICU disease management and its outcome. CONCLUSION: ICU practitioners should be aware of this disease, since it can include life-threatening presentations.

Brachial cuff measurements of blood pressure during passive leg raising for fluid responsiveness prediction.

OBJECTIVE: The passive leg raising maneuver (PLR) for fluid responsiveness testing relies on cardiac output (CO) measurements or invasive measurements of arterial pressure (AP) whereas the initial hemodynamic management during shock is often based solely on brachial cuff measurements. We assessed PLR-induced changes in noninvasive oscillometric readings to predict fluid responsiveness. STUDY DESIGN: Multicentre interventional study. PATIENTS AND METHODS: In ICU sedated patients with circulatory failure, AP (invasive and noninvasive readings) and CO measurements were performed before, during PLR (trunk supine, not modified) and after 500-mL volume expansion. Areas under the ROC curves (AUC) were determined for fluid responsiveness (>10% volume expansion-induced increase in CO) prediction. RESULTS: In 112 patients (19% with arrhythmia), changes in noninvasive systolic AP during PLR (noninvasiveΔ(PLR)SAP) only predicted fluid responsiveness (cutoff 17%, n=21, positive likelihood ratio [LR] of 26 [18-38]), not unresponsiveness. If PLR-induced change in central venous pressure (CVP) was at least of 2 mm Hg (n=60), suggesting that PLR succeeded in altering cardiac preload, noninvasiveΔ(PLR)SAP performance was good: AUC of 0.94 [0.85-0.98], positive and negative LRs of 5.7 [4.6-6.8] and 0.07 [0.009-0.5], respectively, for a cutoff of 9%. Of note, invasive AP-derived indices did not outperform noninvasiveΔ(PLR)SAP. CONCLUSION: Regardless of CVP (i.e., during "blind PLR"), noninvasiveΔ(PLR)SAP more than 17% reliably identified fluid responders. During "CVP-guided PLR", in case of sufficient change in CVP, noninvasiveΔ(PLR)SAP performed better (cutoff of 9%). These findings, in sedated patients who had already undergone volume expansion and/or catecholamines, have to be verified during the early phase of circulatory failure (before an arterial line and/or a CO measuring device is placed).

[Aerosols during mechanical ventilation]. / Aérosols en ventilation mécanique chez l'adulte.

Inhaled therapy is routinely employed during mechanical ventilation. Several factors affect aerosol delivery: the aerosol device, particle size, ventilator parameters, ventilator circuit and hygrometry. Non invasive ventilation is commonly used for treatment of exacerbations of chronic obstructive pulmonary disease. However, there are few data concerning the factors affecting aerosol delivery during this mode of ventilation. Optimal aerosol delivery during mechanical ventilation depends on the aerosol device, the respirator circuit and settings, and the patient himself.

Outbreak in France of Neisseria meningitidis B:15:P1.12 belonging to sequence type 1403.

This report describes a meningococcal outbreak in France caused by Neisseria meningitidis B:15:P1.12 of sequence type 1403, which affected eight young patients, between November 2000 and February 2002. Epidemiological typing confirmed that a single strain was responsible. Favourable outcome, sequelae or death resulted in similar proportions as in other cases of meningococcal disease in France during the same period, but purpura was observed in all eight cases. The patients were aged between 14 and 28 years, whereas the median age of patients affected by other meningococcal strains during this period in the same area was 60.4 years.

Urinary excretion reflects lung deposition of aminoglycoside aerosols in cystic fibrosis.

Using nebulization to deliver aminoglycosides may be of benefit in cystic fibrosis (CF) patients colonized by Pseudomonas aeruginosa. However, one problem with this route is the absence of clinical parameters allowing estimation of the mass of drug deposited in the lungs (MDL). The aim of this study was to assess whether aminoglycoside excretion in the urine reflects the MDL. Fourteen studies were performed in seven CF patients. Amikacin was mixed with albumin labelled with 99mTc and nebulized with an ultrasonic nebulizer. The MDL was determined by the mass-balance technique. Urine was collected during the 24 h following inhalation and was assayed for amikacin by fluorescence polarization immunoassay (FPIA). The mean+/-SEM MDL was 14.0+/-2.2% of the nebulizer charge. The mean+/-SEM amount of amikacin excreted in the urine was 20.9+/-4.5 mg and correlated with the MDL (r=0.93; p=0.0001). There was, however, wide intersubject variability in both deposition and excretion in the urine. Monitoring excretion of aminoglycosides in the urine allows noninvasive estimation of the mass of drug deposited in the lung in cystic fibrosis patients, which might be useful to assess the dose-response relationship in groups of patients, but intersubject variability prevents its use for individual follow-up.

Aerosols and anti-infectious agents.

Anti-infectious agents such as pentamidine, antibiotics (mainly colistine and aminoglycosides), and amphotericin B can be administered by aerosol. Apart from pentamidine and Tobi, this route of administration is not officially approved and it constitutes an empirical approach, which has benefited from recent research summarized hereafter. The most fundamental question is related to the potentially deleterious effects of nebulization processes, especially ultrasound, on the anti-infectious properties of the drugs. Colimycin, which was chosen as a reference because its polypeptide structure makes it unstable a priori, proved to be resistant to high frequency ultrasound, which is encouraging for other molecules such as aminoglycosides or betalactamins. The nebulizer characteristics also have to be taken into account. An aerosol can be produced from an amphotericin B suspension and from colistine using both an ultrasonic nebulizer and a jet nebulizer. Differentiating between good and bad nebulizers is not dependent upon the physical process involved to nebulize the drug, but on the intrinsic characteristics of the device and its performance with a known drug. The inhaled mass of an aerosol in the respirable range must be high and dosimetric nebulizers represent significant progress. Finally, administration of anti-infectious aerosols requires a new pharmacological approach to monitor treatment, and urinary assays are promising for this purpose.

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. DESIGN: Prospective cohort study of patients screened upon admission and 6 months after discharge from the ICU. SETTING: The ICU of a university hospital. PARTICIPANTS: One hundred sixteen consecutive patients age 70 and older admitted to the ICU and treated by mechanical ventilation for at least 24 hours. MEASUREMENTS: A comprehensive medical, functional, nutritional, and social assessment was undertaken for each patient upon admission to the ICU. Functional status and residence were recorded for patients still living 6 months after discharge from the ICU. RESULTS: Mortality in the ICU and 6 months after discharge was 31% and 52%, respectively. The predictors of in-ICU mortality on multivariate analysis were a high omega score per day in the ICU and a high simplified acute physiologic score corrected for points related to age (SAPS IIc). The predictors of mortality at 6 months were a high omega score per day in the ICU, a high SAPS IIc, and a mid-arm circumference (MAC) under the 10th percentile for the older French population in good health. Six months after discharge from the ICU, 91% of the surviving patients had the same residential status and 89% had a similar or improved functional status compared with pre-admission status. CONCLUSIONS: Although severity of illness remains an important predictor of in-ICU mortality and mortality at 6 months after release from ICU, we found that impaired nutritional status upon admission was related to 6-month mortality. These results emphasize the need for a systematic nutritional assessment in older patients admitted to the ICU and treated by mechanical ventilation.

[Microbial infection documented on admission to the intensive care unit for post-chemotherapy neutropenia after empiric antibiotic therapy]. / Infections microbiologiquement documentées à l'admission en réanimation pour neutropénie post-chimiothérapie après antibiothérapie probabiliste.

OBJECTIVE: The purpose of this study was to determine whether a systematic strategy of multiple microbiological samples for all adult patients with neutropenia admitted to an intensive care unit could document sepsis despite prior empiric antibiotic therapy. PATIENTS AND METHODS: All adults admitted to the intensive care unit with chemotherapy-induced neutropenia (WBC < 500/mm3) were included in the study. Microbiological samples were systematically obtained in all patients: 6 blood, 1 stool, 1 urine, 1 nasal swab. Data were analyzed for 54 consecutive patients: 22 men, 32 women, 42 with hematology diseases and 12 with solid tumors, mean age 46.6 +/- 14.4 years. Assessment of disease severity showed: simplified gravity index = 256 +/- 17; organ system failure score on day 1 = 2.42 +/- 1.1; 26 cases of septic shock among 47 cases of sepsis. Mortality was 50%. Within 48 h, bronchioalveolar lavage samples were obtained in 48 patients, and there were 12 spinal taps, 3 laparotomies, 3 skin biopsies and 6 sinus punctures. RESULTS: A microorganism was isolated in 39 patients (70%): 12 Gram negative, 12 Gram positive, 11 mycoses, 3 cases of herpes. Positive cultures were found for 31 blood, 1 bronchioalveolar lavage, 2 surgical, 5 serous and 22 oral or digestive tract samples. Documented microbial infection did not have prognostic value. Septic shock at admission was predictive of poor outcome. DISCUSSION: Despite prior antibiotic therapy in 46 patients, with a theoretically active drug in 37 cases, a systematic strategy of multiple deep samples increased the number of documented cases of infection in neutropenic patients. Oral and digestive tract infections predominated despite selective decontamination of the digestive tract.

[Anti-infective aerosols]. / Les anti-infectieux en aérosols.

Anti-infectious agents such as pentamidine, antibiotics (mainly colistine and aminoglycosides) and amphotericin B can be administered by aerosol. This route of administration is not officially approved and it constitutes an empirical approach which has benefited from recent research which is summarized hereafter. The most fundamental question is related to the potentially deleterious effects of nebulization processes, especially ultrasound, on the anti infectious properties of the drugs. Colimycin, which was chosen as a reference because its polypeptide structure makes it unstable a priori, proved to be resistant to high frequency ultrasound, which is encouraging for other molecules such as aminoglycosides or betalactamins. The nebulizer characteristics have also to be taken into account. An aerosol can be produced from an amphotericin B suspension and from colistine using both an ultrasonic nebulizer and a jet nebulizer. Distinction between good and bad nebulizers does not depend upon the physical process involved to nebulize the drug, but on the intrinsic characteristics of the device and its performance with a known drug. The inhaled mass of an aerosol in the respirable range must be high and dosimetric nebulizers represent a significant progress. Finally, adminnistration of anti infectious aerosols requires a new pharmacological approach to monitor treatment and urinary assays are promising.

Severe non-infectious circulatory shock related to hypopituitarism.

The authors report a case of refractory non-infectious circulatory shock with catecholamine and massive fluid loading-resistant features related to hypopituitarism. A 76-year-old man was admitted for shock after suffering from gastroenteritis for 3 days. He was pale and had sparse axillary and pubic hair and small testes. Right catheterization showed shock with low preload pressure and a low oxygen extraction ratio relevant for septic shock. Ultrasound tomography revealed a distended gallbladder due to a stone without peritoneal effusion. A non-inflammatory hydrops of the gallbladder was removed surgically. No microorganism was isolated. Cerebral computed tomography (CT) scan showed a pituitary mass. In the post-surgical period the shock became uncontrollable. Cortisol replacement therapy was instituted and clinical and hemodynamic improvement occurred after 2 h. Hormonal screening on admission before catecholamine administration showed a major decrease in all the hypothalamic-pituitary hormone concentrations. The patient died on day 15 with multiple organ failure. Hypopituitarism, probably owing to pituitary adenoma, was the only disease identified in this case. Hormone replacement therapy dramatically improved the clinical and hemodynamic status, although the role of an abdominal sepsis could not be eliminated. Arguments that pituitary hormone deficiency might increase the hemodynamic consequences of adrenal deficiency are discussed.

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

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.