Saad Nseir

High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure

BACKGROUND Whether noninvasive ventilation should be administered in patients with acute hypoxemic respiratory failure is debated. Therapy with high-flow oxygen through a nasal cannula may offer an alternative in patients with hypoxemia. METHODS We performed a multicenter, open-label trial in which we randomly assigned patients without hypercapnia who had acute hypoxemic respiratory failure and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 300 mm Hg or less to high-flow oxygen therapy, standard oxygen therapy delivered through a face mask, or noninvasive positive-pressure ventilation. The primary outcome was the proportion of patients intubated at day 28; secondary outcomes included all-cause mortality in the intensive care unit and at 90 days and the number of ventilator-free days at day 28. RESULTS A total of 310 patients were included in the analyses. The intubation rate (primary outcome) was 38% (40 of 106 patients) in the high-flow-oxygen group, 47% (44 of 94) in the standard group, and 50% (55 of 110) in the noninvasive-ventilation group (P=0.18 for all comparisons). The number of ventilator-free days at day 28 was significantly higher in the high-flow-oxygen group (24±8 days, vs. 22±10 in the standard-oxygen group and 19±12 in the noninvasive-ventilation group; P=0.02 for all comparisons). The hazard ratio for death at 90 days was 2.01 (95% confidence interval [CI], 1.01 to 3.99) with standard oxygen versus high-flow oxygen (P=0.046) and 2.50 (95% CI, 1.31 to 4.78) with noninvasive ventilation versus high-flow oxygen (P=0.006). CONCLUSIONS In patients with nonhypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique Interrégional 2010 of the French Ministry of Health; FLORALI ClinicalTrials.gov number, NCT01320384.).

Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit

BACKGROUND The timing of renal-replacement therapy in critically ill patients who have acute kidney injury but no potentially life-threatening complication directly related to renal failure is a subject of debate. METHODS In this multicenter randomized trial, we assigned patients with severe acute kidney injury (Kidney Disease: Improving Global Outcomes [KDIGO] classification, stage 3 [stages range from 1 to 3, with higher stages indicating more severe kidney injury]) who required mechanical ventilation, catecholamine infusion, or both and did not have a potentially life-threatening complication directly related to renal failure to either an early or a delayed strategy of renal-replacement therapy. With the early strategy, renal-replacement therapy was started immediately after randomization. With the delayed strategy, renal-replacement therapy was initiated if at least one of the following criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg per deciliter, or oliguria for more than 72 hours after randomization. The primary outcome was overall survival at day 60. RESULTS A total of 620 patients underwent randomization. The Kaplan-Meier estimates of mortality at day 60 did not differ significantly between the early and delayed strategies; 150 deaths occurred among 311 patients in the early-strategy group (48.5%; 95% confidence interval [CI], 42.6 to 53.8), and 153 deaths occurred among 308 patients in the delayed-strategy group (49.7%, 95% CI, 43.8 to 55.0; P=0.79). A total of 151 patients (49%) in the delayed-strategy group did not receive renal-replacement therapy. The rate of catheter-related bloodstream infections was higher in the early-strategy group than in the delayed-strategy group (10% vs. 5%, P=0.03). Diuresis, a marker of improved kidney function, occurred earlier in the delayed-strategy group (P<0.001). CONCLUSIONS In a trial involving critically ill patients with severe acute kidney injury, we found no significant difference with regard to mortality between an early and a delayed strategy for the initiation of renal-replacement therapy. A delayed strategy averted the need for renal-replacement therapy in an appreciable number of patients. (Funded by the French Ministry of Health; ClinicalTrials.gov number, NCT01932190.).

Risk of acquiring multidrug-resistant Gram-negative bacilli from prior room occupants in the intensive care unit

The objective of this prospective cohort study was to determine whether admission to an intensive care unit (ICU) room previously occupied by a patient with multidrug-resistant (MDR) Gram-negative bacilli (GNB) increases the risk of acquiring these bacteria by subsequent patients. All patients hospitalized for >48 h were eligible. Patients with MDR GNB at ICU admission were excluded. The MDR GNB were defined as MDR Pseudomonas aeruginosa, Acinetobacter baumannii and extended spectrum β-lactamase (ESBL) -producing GNB. All patients were hospitalized in single rooms. Cleaning of ICU rooms between two patients was performed using quaternary ammonium disinfectant. Risk factors for MDR P. aeruginosa, A. baumannii and ESBL-producing GNB were determined using univariate and multivariate analysis. Five hundred and eleven consecutive patients were included; ICU-acquired MDR P. aeruginosa was diagnosed in 82 (16%) patients, A. baumannii in 57 (11%) patients, and ESBL-producing GNB in 50 (9%) patients. Independent risk factors for ICU-acquired MDR P. aeruginosa were prior occupant with MDR P. aeruginosa (OR 2.3, 95% CI 1.2-4.3, p 0.012), surgery (OR 1.9, 95% CI 1.1-3.6, p 0.024), and prior piperacillin/tazobactam use (OR 1.2, 95% CI 1.1-1.3, p 0.040). Independent risk factors for ICU-acquired A. baumannii were prior occupant with A. baumannii (OR 4.2, 95% CI 2-8.8, p <0.001), and mechanical ventilation (OR 9.3, 95% CI 1.1-83, p 0.045). Independent risk factors for ICU-acquired ESBL-producing GNB were tracheostomy (OR 2.6, 95% CI 1.1-6.5, p 0.049), and sedation (OR 6.6, 95% CI 1.1-40, p 0.041). We conclude that admission to an ICU room previously occupied by a patient with MDR P. aeruginosa or A. baumannii is an independent risk factor for acquisition of these bacteria by subsequent room occupants. This relationship was not identified for ESBL-producing GNB.

Nosocomial tracheobronchitis in mechanically ventilated patients: incidence, aetiology and outcome

The aim of this study was to determine the incidence, the organisms responsible for and the impact on outcome of nosocomial tracheobronchitis (NTB) in the intensive care unit (ICU). This prospective observational cohort study was conducted in a 30-bed medical/surgical ICU over a period of 6.5 yrs. All patients ventilated for >48 h were eligible. Patients with nosocomial pneumonia (NP) without prior NTB were excluded. Patients with first episodes of NTB were compared with those without NTB by univariate analysis. The study diagnosed 201 (10.6%) cases of NTB. Pseudomonas aeruginosa was the most common bacteria. NP rates were similar in patients with NTB compared with patients without NTB. Even in the absence of subsequent NP, NTB was associated with a significantly higher length of ICU stay and duration of mechanical ventilation in both surgical and medical populations. Mortality rates were similar in NTB patients without subsequent NP compared with patients without NTB. Antimicrobial treatment in NTB patients was associated with a trend to a better outcome. Nosocomial tracheobronchitis is common in mechanically ventilated intensive care unit patients. In this population, nosocomial tracheobronchitis was associated with longer durations of intensive care unit stay and mechanical ventilation. Further studies are needed to determine the impact of antibiotics on outcomes of patients with nosocomial tracheobronchitis.

Continuous Control of Tracheal Cuff Pressure and Microaspiration of Gastric Contents in Critically Ill Patients

RATIONALE Underinflation of the tracheal cuff frequently occurs in critically ill patients and represents a risk factor for microaspiration of contaminated oropharyngeal secretions and gastric contents that plays a major role in the pathogenesis of ventilator-associated pneumonia (VAP). OBJECTIVES To determine the impact of continuous control of tracheal cuff pressure (P(cuff)) on microaspiration of gastric contents. METHODS Prospective randomized controlled trial performed in a single medical intensive care unit. A total of 122 patients expected to receive mechanical ventilation for at least 48 hours through a tracheal tube were randomized to receive continuous control of P(cuff) using a pneumatic device (intervention group, n = 61) or routine care of P(cuff) (control group, n = 61). MEASUREMENTS AND MAIN RESULTS The primary outcome was microaspiration of gastric contents as defined by the presence of pepsin at a significant level in tracheal secretions collected during the 48 hours after randomization. Secondary outcomes included incidence of VAP, tracheobronchial bacterial concentration, and tracheal ischemic lesions. The pneumatic device was efficient in controlling P(cuff). Pepsin was measured in 1,205 tracheal aspirates. Percentage of patients with abundant microaspiration (18 vs. 46%; P = 0.002; OR [95% confidence interval], 0.25 [0.11-0.59]), bacterial concentration in tracheal aspirates (mean ± SD 1.6 ± 2.4 vs. 3.1 ± 3.7 log(10) cfu/ml, P = 0.014), and VAP rate (9.8 vs. 26.2%; P = 0.032; 0.30 [0.11-0.84]) were significantly lower in the intervention group compared with the control group. However, no significant difference was found in tracheal ischemia score between the two groups. CONCLUSIONS Continuous control of P(cuff) is associated with significantly decreased microaspiration of gastric contents in critically ill patients.

Metformin-associated lactic acidosis: a prognostic and therapeutic study.

Objectives: Metformin-associated lactic acidosis is a rare and serious complication of biguanide treatment. It usually occurs when a precipitating disease induces an acute renal failure and an incidental overdose. Voluntary intoxication is rare. Bicarbonate hemodialysis (HD) is recommended to decrease metformin levels and correct acidosis but its optimal duration has not been determined. This study was designed to document the characteristics and prognostic factors of intentional and incidental metformin overdose and to determine the optimal duration of HD. Design: Ten years retrospective analysis of patients admitted in intensive care unit for metformin-associated lactic acidosis. Setting: Two intensive care units (50 beds) in a university hospital. Measurements and Main Results: Clinical and biological characteristics, organ failures, and sequential metformin levels during HD were recorded. Forty-two patients were included (13 voluntary intoxications and 29 incidental overdoses); 74% of patients were in acute renal failure and needed HD. No death was observed in intentional overdose patients compared with 48.3% mortality in incidental overdose patients. The factors significantly associated with mortality were logistic organ dysfunction system score, pH, plasma lactate, and prothrombin activity. By multivariate analysis, a prothrombin activity <50% was the only independent predictive factor of mortality (relative risk: 59.8; confidence limits: 6.3–568; p < 0.0001). Sequential measurements of metformin levels during HD were consistent with a bicompartmental elimination pattern. A cumulative HD duration of 15 hours was associated with the return of metformin level to the therapeutic normal range. Conclusions: In our study, the outcome of MALA was uniformly favorable after intentional metformin overdose. The vital prognosis was mainly influenced by the occurrence of multiple organ dysfunctions, the best predictive factor of death being an acute liver dysfunction as assessed by PT activity. Prolonged HD was needed to correct metformin overdose.

Antimicrobial treatment for ventilator-associated tracheobronchitis: a randomized, controlled, multicenter study

IntroductionVentilator-associated tracheobronchitis (VAT) is associated with increased duration of mechanical ventilation. We hypothesized that, in patients with VAT, antibiotic treatment would be associated with reduced duration of mechanical ventilation.MethodsWe conducted a prospective, randomized, controlled, unblinded, multicenter study. Patients were randomly assigned (1:1) to receive or not receive intravenous antibiotics for 8 days. Patients with ventilator-associated pneumonia (VAP) prior to VAT and those with severe immunosuppression were not eligible. The trial was stopped early because a planned interim analysis found a significant difference in intensive care unit (ICU) mortality.ResultsFifty-eight patients were randomly assigned. Patient characteristics were similar in the antibiotic (n = 22) and no antibiotic (n = 36) groups. Pseudomonas aeruginosa was identified in 32% of VAT episodes. Although no difference was found in mechanical ventilation duration and length of ICU stay, mechanical ventilation-free days were significantly higher (median [interquartile range], 12 [8 to 24] versus 2 [0 to 6] days, P < 0.001) in the antibiotic group than in the no antibiotic group. In addition, subsequent VAP (13% versus 47%, P = 0.011, odds ratio [OR] 0.17, 95% confidence interval [CI] 0.04 to 0.70) and ICU mortality (18% versus 47%, P = 0.047, OR 0.24, 95% CI 0.07 to 0.88) rates were significantly lower in the antibiotic group than in the no antibiotic group. Similar results were found after exclusion of patients with do-not-resuscitate orders and those randomly assigned to the no antibiotic group but who received antibiotics for infections other than VAT or subsequent VAP.ConclusionIn patients with VAT, antimicrobial treatment is associated with a greater number of days free of mechanical ventilation and lower rates of VAP and ICU mortality. However, antibiotic treatment has no significant impact on total duration of mechanical ventilation.Trial registrationClinicalTrials.gov, number NCT00122057.

First-generation fluoroquinolone use and subsequent emergence of multiple drug-resistant bacteria in the intensive care unit*

Objective:The objective of this study was to determine the relationship between fluoroquinolone (FQ) use and subsequent emergence of multiple drug-resistant bacteria (MRB) in the intensive care unit (ICU). Design:The authors conducted a prospective observational cohort study and a case control study. Setting:The study was conducted in a 30-bed ICU. Methods:All immunocompetent patients hospitalized for >48 hrs who did not receive antibiotics before ICU admission were eligible during a 15-month period. Routine MRB screening was performed at ICU admission and weekly thereafter. This screening included tracheal aspirate and nasal, anal, and axilla swabs. Univariate and multivariate analyses were used to determine risk factors for MRB emergence in the ICU. In addition, a case control study was performed to determine whether FQ use is associated with subsequent emergence of MRB. Results:Two hundred thirty-nine patients were included; 108 ICU-acquired MRB were isolated in 77 patients. FQ use and longer duration of antibiotic treatment were identified as independent risk factors for MRB occurrence (odds ratio [95% confidence interval [CI] = 3.3 [1.7–6.5], 1.1 [1.0–1.2]; p < .001; respectively). One hundred thirty-five (56%) patients received FQ; matching was successful for 72 (53%) of them. Number of MRB (40 vs. 15 per 1,000 ICU days; p = .019) and percentage of patients with MRB (40% vs. 22%; OR [95% CI] = 1.5 [1.0–2.4]; p = .028) were significantly higher in cases than in controls. Although methicillin-resistant Staphylococcus aureus (26% vs. 12%; OR [95% CI] = 1.6 [.6–2.9]; p = .028) and extending-spectrum &bgr;-lactamase-producing Gram-negative bacilli (11% vs. 1%; OR [95% CI] = 4.7 [0.7–30.2]; p = .017) rates were higher in cases than in controls, ceftazidime or imipenem-resistant Pseudomonas aeruginosa (15% vs. 8%), Acinetobacter baumannii (1% vs. 5%), and Stenotrophomonas maltophilia (2% vs. 1%) rates were similar (p > .05) in case and control patients. Conclusion:FQ use and longer duration of antibiotic treatment are independently associated with MRB emergence. Reducing antimicrobial treatment duration and restricting FQ use could be suggested to control MRB spread in the ICU.

Preliminary clinical study using a multiplex real‐time PCR test for the detection of bacterial and fungal DNA directly in blood

Early diagnosis of sepsis, rapid identification of the causative pathogen(s) and prompt initiation of appropriate antibiotic treatment have a combined impact on mortality due to sepsis. In this observational study, a new DNA-based system (LightCycler SeptiFast (LC-SF) test; Roche Diagnostics) allowing detection of 16 pathogens at the species level and four groups of pathogens at the genus level has been evaluated and compared with conventional blood cultures (BCs). One hundred BC and LC-SF results were obtained for 72 patients admitted to the intensive-care unit over a 6-month period for suspected sepsis. Microbiological data were compared with other biological parameters and with clinical data. The positivity rate of BCs for bacteraemia/fungaemia was 10%, whereas the LC-SF test allowed detection of DNA in 15% of cases. The LC-SF performance, based on its clinical relevance, was as follows: sensitivity, 78%; specificity, 99%; positive predictive value, 93%; and negative predictive value, 95%. Management was changed for four of eight (50%) of the patients because organisms were detected by the LC-SF test but not by BC. LC-SF results were obtained in 7-15 h, in contrast to the 24-72 h required for BC. According to the LC-SF results, initial therapy was inadequate in eight patients, and antibiotic treatment was changed. Our results suggest that the LC-SF test may be a valuable complementary tool in the management of patients with clinically suspected sepsis.

Continuous control of endotracheal cuff pressure and tracheal wall damage: a randomized controlled animal study

BackgroundIntubation is frequently performed in intensive care unit patients. Overinflation of the endotracheal tube cuff is a risk factor for tracheal ischemia and subsequent complications. Despite manual control of the cuff pressure, overinflation of the endotracheal cuff is common in intensive care unit patients. We hypothesized that efficient continuous control of the endotracheal cuff pressure using a pneumatic device would reduce tracheal ischemic lesions in piglets ventilated for 48 hours through a high-volume, low-pressure endotracheal tube.Materials and methodsTwelve piglets were intubated and mechanically ventilated for 48 hours. Animals were randomized to manual control of the endotracheal cuff pressure (n = 6) or to continuous control of the endotracheal cuff pressure using a pneumatic device (n = 6). In the two groups, we inflated the endotracheal cuff with 50 ml air for 30 minutes, eight times daily. This hyperinflation of the endotracheal cuff aimed at mimicking high-pressure periods observed in intubated critically ill patients. In all animals, the cuff pressure and the airway pressure were continuously recorded for 48 hours. After sacrifice of the study animals, the trachea was removed and opened longitudinally for gross and histological examination. A pathologist evaluated the slides without knowledge of treatment group assignment.ResultsThe cuff pressure was significantly lower in piglets with the pneumatic device than in piglets without the pneumatic device (median (interquartile range), 18.6 (11–19.4) cmH2O versus 26 (20–56) cmH2O, P = 0.009). No significant difference was found in the percentage of time spent with a cuff pressure <15 cmH2O and that with a cuff pressure between 30 and 50 cmH2O. The percentage of time between 15 and 30 cmH2O of cuff pressure, however, was significantly higher in piglets with the pneumatic device than in piglets without the pneumatic device (98% (95–99%) versus 65% (44–80%), P = 0.002). In addition, the percentage of time with cuff pressure >50 cmH2O was significantly lower in piglets with the pneumatic device than in piglets without the pneumatic device (0% versus 19% (12–41%), P = 0.002).In all animals, hyperemia and hemorrhages were observed at the cuff contact area. Histological examination showed no difference in tracheal lesions between animals with and without the pneumatic device. These lesions included deep mucous ulceration, squamous metaplasia and intense mucosal inflammation. No cartilage lesions were observed.ConclusionThe pneumatic device provided effective continuous control of high-volume, low-pressure endotracheal cuff pressure in piglets mechanically ventilated for 48 hours. In the present model, however, no significant difference was found in tracheal mucosal lesions of animals with or without a pneumatic device. Further studies are needed to determine the impact of continuous control of cuff pressure over a longer duration of mechanical ventilation.