Philippe R. Bauer

Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study

Objectives: To compare the effects of norepinephrine and dobutamine to epinephrine on hemodynamics, lactate metabolism, and gastric tonometric variables in hyperdynamic dopamine-resistant septic shock. Design: A prospective, intervention, randomized clinical trial. Setting: Adult medical/surgical intensive care unit in a university hospital. Patients: 30 patients with a cardiac index (CI) > 3.5 l · min–1· m–2 and a mean arterial pressure (MAP) ≤ 60 mmHg after volume loading and dopamine 20 μg/kg per min and either oliguria or hyperlactatemia. Interventions: Patients were randomized to receive an infusion of either norepinephrine-dobutamine or epinephrine titrated to obtain an MAP greater than 80 mmHg with a stable or increased CI. Measurements and main results: Baseline measurements included: hemodynamic and tonometric parameters, arterial and mixed venous gases, and lactate and pyruvate blood levels. These measurements were repeated after 1, 6, 12, and 24 h. All the patients fulfilled the therapeutic goals. No statistical difference was found between epinephrine and norepinephrine-dobutamine for systemic hemodynamic measurements. Considering metabolic and tonometric measurements and compared to baseline values, after 6 h, epinephrine infusion was associated with an increase in lactate levels (from 3.1 ± 1.5 to 5.9 ± 1.0 mmol/l; p < 0.01), while lactate levels decreased in the norepinephrine-dobutamine group (from 3.1 ± 1.5 to 2.7 ± 1.0 mmol/l). The lactate/pyruvate ratio increased in the epinephrine group (from 15.5 ± 5.4 to 21 ± 5.8; p < 0.01) and did not change in the norepinephrine-dobutamine group (13.8 ± 5 to 14 ± 5.0). Gastric mucosal pH (pHi) decreased (from 7.29 ± 0.11 to 7.16 ± 0.07; p < 0.01) and the partial pressure of carbon dioxide (PCO2) gap (tonometer PCO2– arterial PCO2) increased (from 10 ± 2.7 to 14 ± 2.7 mmHg; p < 0.01) in the epinephrine group. In the norepinephrine-dobutamine group pHi (from 7.30 ± 0.11 to 7.35 ± 0.07) and the PCO2 gap (from 10 ± 3.0 to 4 ± 2.0 mmHg) were normalized within 6 h (p < 0.01). The decrease in pHi and the increase in the lactate/pyruvate ratio in the epinephrine group was transient, since it returned to normal within 24 h. Conclusions: Considering the global hemodynamic effects, epinephrine is as effective as norepinephrine-dobutamine. Nevertheless, gastric mucosal acidosis and global metabolic changes observed in epinephrine-treated patients are consistent with a markedly inadequate, although transient, splanchnic oxygen utilization. The metabolic and splanchnic effects of the combination of norepinephrine and dobutamine in hyperdynamic dopamine-resistant septic shock appeared to be more predictable and more appropriate to the current goals of septic shock therapy than those of epinephrine alone.

Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome. Insights from the LUNG SAFE Study

Rationale: Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse. Objectives: To determine whether, during NIV, the categorization of ARDS severity based on the PaO2/FiO2 Berlin criteria is useful. Methods: The LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of the PaO2/FiO2 ratio in classifying patients receiving NIV, and the impact of NIV on outcome. Measurements and Main Results: Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on PaO2/FiO2 ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1% and 45.4%, respectively. NIV use was independently associated with increased ICU (hazard ratio, 1.446 [95% confidence interval, 1.159‐1.805]), but not hospital, mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a PaO2/FiO2 lower than 150 mm Hg. Conclusions: NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV seems to be associated with higher ICU mortality in patients with a PaO2/FiO2 lower than 150 mm Hg. Clinical trial registered with www.clinicaltrials.gov (NCT 02010073).

Therapeutic optimization including inhaled nitric oxide in adult respiratory distress syndrome in a polyvalent intensive care unit.

OBJECTIVE To investigate the effects of inhaled nitric oxide (NO) in adult respiratory distress syndrome (ARDS) associated with a therapeutic optimization strategy on oxygen parameters, barotrauma, and evolution in a medical and surgical intensive care unit. DESIGN Prospective study. MATERIALS AND METHODS Twenty consecutive patients with ARDS were studied (Murray score 3.6 +/- 0.2). Eleven were surgical patients and nine were medical patients. All fulfilled the extracorporeal membrane oxygenation entry criteria. The APACHE II score predicted mortality was 39%. All were ventilated with FiO2 1 with positive end-expiratory pressure (PEEP) of 11 +/- 1 cm H2O. Therapeutic optimization included permissive hypercapnia, tracheal gas insufflation, prone position, continuous hemofiltration, treatment of infection, and pleural drainage. We used NO continuously inhaled at a concentration ranging from 5 to 10 ppm. MEASUREMENTS AND MAIN RESULTS After 1 hour, inhaled NO improved PaO2 in all patients except one (78 +/- 11 to 130 +/- 25 mm Hg) (p < 0.05), allowing a reduction of FiO2 and PEEP. After 24 hours, mean pulmonary arterial pressure decreased from 31 +/- 3 to 25 +/- 2 mm Hg (p < 0.05). Systemic hemodynamics were unaffected. Oxygen delivery increased from 531 +/- 135 to 603 +/- 125 mL/minute/m-2 (p < 0.05). Barotraumatic lesions were present in only one patient. Reversal of ARDS was obtained in 16 patients, of whom 14 (70%) were discharged. CONCLUSIONS This study was shorter to demonstrate an improvement in the survival rate. Nevertheless, these preliminary results are encouraging. Because of its safety, effectiveness, and easy use, inhaled NO should be used as a part of a therapeutic optimization protocol before considering more invasive and expensive procedures, such as extracorporeal respiratory support or intravascular oxygenation.

Influence of dexmedetomidine therapy on the management of severe alcohol withdrawal syndrome in critically ill patients

PURPOSE Although benzodiazepines are first-line drugs for alcohol withdrawal syndrome (AWS), rapidly escalating doses may offer little additional benefit and increase complications. The purpose of this study was to evaluate dexmedetomidines impact on benzodiazepine requirements and hemodynamics in AWS. MATERIALS AND METHODS This retrospective case series evaluated 33 critically ill adults with a primary diagnosis of AWS from 2006 to 2012 at an academic medical center. RESULTS Dexmedetomidine began a median (interquartile range) of 11 (2, 32) hours into intensive care unit admission and was titrated to an infusion rate of 0.7 (0.4, 0.7) μg kg(-1) h(-1) to achieve the desired depth of sedation. In the 12 hours after dexmedetomidine began, patients experienced a 20-mg reduction in median cumulative benzodiazepine dose used (P < .001), a 14-mm Hg lower mean arterial pressure (P = .03), and a 17-beats/min reduction in median heart rate (P < .001). Four (12%) patients experienced hypotension (systolic blood pressure <80 mm Hg) during therapy, and there were no cases of bradycardia (heart rate <40 beats/min). CONCLUSION Dexmedetomidine decreased benzodiazepine requirements and improved the overall hemodynamic profile of patients with severe AWS. These results provide promising evidence about the potential benefit of dexmedetomidine for AWS.

Amyloid-associated cystic lung disease in primary Sjögren's syndrome

BACKGROUND Cystic lung disease can be seen in patients with Sjögrens syndrome (SS) and is generally thought to be due to lymphocytic interstitial pneumonia. METHODS Using computer-assisted search we identified patients with primary SS seen at Mayo Clinic, Rochester, MN during a 14-year period from 1997 to 2010 who were diagnosed with pulmonary amyloidosis confirmed on lung biopsy. Clinical records, imaging studies, and pathologic specimens were reviewed to delineate presenting features, diagnostic evaluation, and clinical course. RESULTS Eight patients (7 women, 1 man) with primary SS were diagnosed with pulmonary amyloidosis by lung biopsy (7 surgical, 1 bronchoscopic). Their median age was 55 years (range, 32-75 years) and all were nonsmokers. Presenting symptoms included dyspnea and cough but 4 patients presented with radiologic abnormalities in the absence of respiratory symptoms. CT findings included cystic lesions and nodular opacities in all eight patients. PET scan performed in six patients did not reveal (18)F-2-deoxyglucose (FDG) uptake except in one nodule with borderline uptake. Lung biopsy demonstrated the presence of amyloid in all patients and was associated with mucosa-associated lymphoid tissue (MALT) lymphoma in three patients. Pulmonary function results were normal in five patients and revealed mild impairment in a mixed pattern in one patient. CONCLUSIONS We conclude cystic and nodular lung lesions seen in patients with primary SS can represent amyloidosis which can be associated with MALT lymphoma in some of these patients.

Multiple European wasp stings and acute renal failure

Dr. Lionel Nace, Service de Réanimation Médicale, Hôpital Central, F-54035 Nancy Cedex (France) Table 1. Biological data Day Normal values Dear Sir, We report a case of acute renal failure (ARF) without hemolysis or rhabdomyolysis after multiple wasp stings. ARF after multiple stings from the hymen-optera species is a well-known [1] but still rare phenomenon (18 cases) [2-7] and its occurrence is exceptional in European countries with only 1 case reported [7]. Then, ARF is related to an acute tubular necrosis due to rhabdomyolysis or intravascular hemolysis. A 56-year-old man with no history of renal disease was stung in the north-east of France by a swarm of wasps (vespula germanica?); between 20 and 30 stings were located on both upper limbs and the face. He was first treated with dexamethasone and HI histamine inhibitors. During the first 12 h the patient felt unwell with a gastroenteritis-like syndrome. At a local hospital, 18 h after poisoning, no shock was observed. Fourty-eight hours after poisoning, he developed ARF with oligoanuria and was transferred to our intensive care unit. On admission, blood pressure was 130/60 mm Hg, uri-nalysis was normal and diuresis was restored after diuretic administration (see biological data in table 1). Moreover, no hemolysis was observed (no hemoglobinuria, free hemoglobin and haptoglobin level within normal ranges). A normal renal angiography discarded any renal vascular lesion. In spite of urine flow restoration, ARF got worse and required hemodialysis on the 3rd day. Then, renal function improved gradually and had returned to normal 3 months later. No kidney biopsy was performed. In the literature, ARF after wasp stings is attributed to rhabdomyolysis or hemolysis. Rhabdomyolysis seems secondary to the poia Stings. b Admission. soning action of phospholipases, polypep-tides, histamine and serotonine from wasp venom [2,3,8]. In the same way, intravascular hemolysis appears related to phospholipase A and basic protein fractions [2]. In both cases, intraglomerular clotting of myoglobin or hemoglobin induces ARF.

Influence of interstitial lung disease on outcome in systemic sclerosis: A population-based historical cohort study

BACKGROUND Interstitial lung disease (ILD) is a frequent complication of systemic sclerosis (SSc) and a major cause of SSc-related deaths. This study aimed to determine the influence of ILD on SSc in a population-based historical cohort study. The hypothesis was that patients with SSc who develop ILD have increased morbidity and mortality when compared with patients with SSc without ILD. METHODS Using the record linkage system of the Rochester Epidemiology Project in Olmsted County, Minnesota, this study identified the incidence of SSc between 1980 and 2010 and point prevalence on December 31, 2010 and determined the progression of organ involvement and its influence on outcome. RESULTS During the 30-year interval, we identified 64 incident cases of SSc: 57 women and seven men, median age 49.1 years (interquartile range [IQR], 39.8-67.6 years). There were 43 prevalent cases. ILD occurred in 19 cases, usually after the diagnosis of SSc (median, 2 years; IQR, 0-10 years), with only three cases occurring 6 to 24 months beforehand. Pulmonary arterial hypertension (PAH) was diagnosed in 14 cases, heart failure in 27 cases, and chronic kidney disease (CKD) in 21 cases. Seventeen patients died during the study period, with a median survival time after diagnosis of 22.9 years. ILD, PAH, and CKD were associated with an increased risk of death. CONCLUSIONS The incidence of ILD associated with SSc was relatively low in this population-based cohort. ILD appeared to be a contributing factor to mortality. Other factors, including age, PAH, and CKD, were also associated with poor outcome.

Influence of autoimmune biomarkers on interstitial lung diseases: A tertiary referral center based case-control study

Background The benefit of routinely measuring autoimmune biomarkers to evaluate patients with interstitial lung disease (ILD) remains debated outside specific contexts such as connective tissue disease (CTD). This study aimed at evaluating the influence of biomarkers on outcome on patients with ILD in a case-control study at a tertiary referral center. We hypothesized that patients with positive autoimmune biomarkers have increased odds of developing ILD even in the absence of CTD. Methods We reviewed the medical records of 3573 patients seen at the ILD clinic in Mayo Clinic Rochester between September 2001 and September 2006. We assessed their clinical course through June 25, 2013. We included patients with patterns of ILD most often associated with CTD (n=1256) while excluding patients with other known causes of ILD. Controls (n=2317) included cases seen at the ILD clinic without evidence of ILD. Results We identified 930 (26%) cases of ILD alone, 124 (3%) CTD alone, 326 (9%) ILD combined with CTD, and 2193 (61%) with no ILD or CTD. Positive antinuclear antibodies (ANA), rheumatoid factor and aldolase were associated with ILD. After adjustment for age, gender, race, smoking history and CTD, ANA remained an independent risk factor for ILD (OR 1.70, 95% CI 1.33–2.17). Among patients with ILD, the presence of CTD but not biomarker alone was associated with a better survival. Conclusion In this study, the presence of positive biomarkers was associated with increased odds of ILD, even in the absence of overt CTD, but was not associated with a better outcome.

The Intensive Care Medicine research agenda on critically ill oncology and hematology patients

Over the coming years, accelerating progress against cancer will be associated with an increased number of patients who require life-sustaining therapies for infectious or toxic chemotherapy-related events. Major changes include increased number of cancer patients admitted to the ICU with full-code status or for time-limited trials, increased survival and quality of life in ICU survivors, changing prognostic factors, early ICU admission for optimal monitoring, and use of noninvasive diagnostic and therapeutic strategies. In this review, experts in the management of critically ill cancer patients highlight recent changes in the use and the results of intensive care in patients with malignancies. They seek to put forward a standard of care for the management of these patients and highlight important updates that are required to care for them. The research agenda they suggest includes important studies to be conducted in the next few years to increase our understanding of organ dysfunction in this population and to improve our ability to appropriately use life-saving therapies or select new therapeutic approaches that are likely to improve outcomes. This review aims to provide more guidance for the daily management of patients with cancer, in whom outcomes are constantly improving, as is our global ability to fight against what is becoming the leading cause of mortality in industrialized and non-industrialized countries.

SELENIUM, OXYGEN-DERIVED FREE RADICALS, AND ISCHEMIA-REPERFUSION INJURY : AN EXPERIMENTAL STUDY IN THE RAT

Circulatory shock and its treatment have been compared to a whole-body ischemia and reperfusion with activation of oxygen-derived free radicals. A pilot study had suggested a selenium redistribution in this context. To verify this hypothesis, an experimental study was designed. Temporary occlusion of the superior mesenteric artery was performed in 18 male adult Wistar rats using clamping for 0, 10, and 20 min. Hemodynamic and biochemical data were assessed before clamping and 20 min after release of the mesenteric blood flow. After release, mean arterial pressure decreased, plasma lactate increased, and erythrocyte glutathione peroxidase decreased. Plasma and erythrocyte selenium did not change; however, a slight decrease in plasma selenium was observed when related to hematocrit (to take into account the fluid balance). Erythrocyte-reduced glutathione did not change. In contrast, liver and kidney selenium increased, whereas reduced glutathione decreased in kidney, but not in liver after 20 min of clamping as compared to the sham-operated group. These results suggest that, after temporary intestinal ischemia, the changes in selenium and reduced glutathione observed in blood and tissues, like liver or kidney, could be related to a redistribution pattern in selenium metabolism during shock injury.