Reduced Red Cell 2,3-Diphosphoglycerate Concentrations in Critical Illness without Decreased In Vivo P50

We investigated whether red cell 2,3-diphosphoglycerate (2,3-DPG) concentrations are reduced in critical illness, whether acidaemia, hypophosphataemia or anaemia influence 2,3-DPG, and whether there is any net effect on in vivo P50. Twenty healthy, non-smoking, male volunteers were compared with 20 male intensive care patients with APACHE 2 scores > 20 on the preceding day. Those transfused in this time were excluded. Venous red cell 2,3-DPG concentrations were measured in both groups. In the patient group, routine multichannel biochemical profile and arterial blood gas analysis were also performed and in vivo P50 calculated. The mean 2,3-DPG concentration was significantly lower in the patient group than in the controls (4.2 +/-1.3 mmoll/l vs 4.9 +/-0.5 mmol/l, P=0.016). The patients were well oxygenated (lowest arterial PO2=75 mm Hg) and showed a tendency to acidaemia (median pH 7.37, range 7.06 to 7.48) and anaemia (median haemoglobin concentration 113 g/l, range 89 to 154 g/l). By linear regression of patient data, pH had a significant effect on 2,3-DPG concentrations (r=0.6, P=0.011). Haemoglobin and phosphate concentrations did not, but there were few abnormal phosphate values. There was no correlation between 2,3-DPG concentrations and in vivo P50 (r(2) less than or equal to 0.08). We conclude that 2,3-DPG concentrations were reduced in a broad group of critically ill patients. Although this would normally reduce the P50, the reduction was primarily linked with acidaemia, which increases the P50. Overall, there was no net effect on the P50 and thus no affinity-related decrease in tissue oxygenation.

The 2009 Pandemic Influenza A (H1N1) Infection: Renal Histopathology Findings in Two Infected Patients

Background: Acute kidney injury in the pandemic swine origin influenza A virus (H1N1) infection has been reported as coursing with severe illness, although renal pathogenic mechanisms and histologic features are still being characterised. Case Report: We present two patients admitted with H1N1 pneumonia, sepsis, acute respiratory distress syndrome and need for invasive mechanical ventilation who developed acute kidney injury and became dialysis-dependent. In both cases a kidney biopsy was performed to establish a definitive diagnosis. Severe acute tubular necrosis was identified, with no further abnormalities. Conclusion: This report seems to confirm that the acute kidney injury in H1N1 infection is focused on the tubular cells. Our cases corroborate the renal histopathologic findings of other studies, highlighting the central role of the tubular cell. We bring new evidence of the histopathology of AKI in H1N1 infection since our data were collected in living patients and not via post-mortem studies.

In vitro activity of the clinical pulmonary surfactant Surfacen® against Leishmania amazonensis

Surfacen® is an exogenous natural lung surfactant, composed by phospholipids and hydrophobic proteins, which is applied successfully in Newborn Respiratory Distress Syndrome. In this paper, in vitro activity of Surfacen® against Leishmania amazonensis is described. The product showed activity against the amastigote form found in peritoneal macrophages from BALB/c mice, with an IC50 value of 17.9 ± 3.0 µg/mL; while no toxic effect on host cell was observed up to 200 µg/mL. This is the first report about the antileishmanial activity of Surfacen®.

Colestase Intra-Hepática da Gravidez: Fator de Risco para Síndrome de Dificuldade Respiratória Neonatal?

Introdução: A colestase intra-hepática da gravidez está associada a complicações fetais e neonatais graves, incluindo síndrome de dificuldade respiratória. Tem sido recomendada terapêutica materna com ácido ursodesoxicólico e antecipação do parto para reduzir o risco de complicações. Os objetivos foram determinar a associação entre colestase intra-hepática da gravidez e síndrome de dificuldade respiratória neonatal e avaliar a relação com níveis maternos de ácidos biliares e procedimentos perinatais. Metodologia: Estudo caso-controlo incluindo grávidas com colestase intra-hepática da gravidez e respetivos recém-nascidos (grupo colestase), com parto numa maternidade portuguesa de nível III entre 2006 e 2010. Os controlos foram emparelhados para idade gestacional e peso ao nascimento (1 caso para 2 controlos). Resultados: Foram incluídas 42 grávidas com colestase intra-hepática da gravidez (incidência 0,15%) e 53 recém- -nascidos. Dez recém-nascidos do grupo colestase (19,2%) e 14 controlos (13,7%) tiveram dificuldade respiratória(p=0,375). A FiO2 máxima foi superior no grupo colestase (mediana 34,0% vs. 25,0%; p=0,294), mas sem diferença quanto à ventilação mecânica. A idade gestacional ao diagnóstico de colestase materna foi menor nos recém-nascidos com dificuldade respiratória (mediana 30,5 vs 33,5 semanas; p=0,024). A taxa de parto desencadeado iatrogenicamente(69,8% vs. 40,6%; p=0,001; OR=3,4), cesariana (66,0% vs 44,3%; p=0,01; OR=2,4) e corticoterapia pré-natal (43,4% vs. 25,5%; p=0,022) foi significativamente maior no grupo colestase. Não se encontrou relação entre dificuldade respiratória neonatal e níveis maternos de ácidos biliares nem terapêutica materna com ácido ursodesoxicólico. Conclusão: A colestase intra-hepática da gravidez, sobretudo de início precoce, está tendencialmente associada a síndrome de dificuldade respiratória neonatal. A antecipação do parto traz riscos adicionais para os recém-nascidos. A corticoterapia pré-natal neste contexto pode ter mascarado a verdadeira incidência de dificuldade respiratória neonatal.

Acute Eosinophilic and Neutrophilic Pneumonia following Transarterial Chemoembolization with Drug-Eluting Beads Loaded with Doxorubicin for Hepatocellular Carcinoma: A Case Report.

At an intermediate or advanced stage, i.e. stage B or C, based on the Barcelona Clinic Liver Cancer classification of hepatocellular carcinoma (HCC), transarterial chemoembolization (TACE) may be offered as a treatment of palliative intent. We report the case of a patient suffering from acute respiratory distress syndrome after TACE with drug-eluting beads loaded with doxorubicin for HCC. To our knowledge, this is the first case described where a bronchoalveolar lavage was performed, and where significant levels of alveolar eosinophilia and neutrophilia were evident, attributed to a pulmonary toxicity of doxorubicin following liver chemoembolization. © 2014 S. Karger AG, Basel.

Cytokine levels in bronchoalveolar lavage and serum in 3 patients with 2009 influenza A(H1N1)v severe pneumonia.

Introduction: Pandemic Influenza A (H1N1)v pneumonia has led to a notable increase of admissions to intensive care units. A cytokine-mediated inflammatory response has been well documented in pneumonia and acute respiratory distress syndrome. However, few studies have focused on the role of these inflammatory mediators in infections caused by the Influenza A (H1N1)v. In this study, we assess the inflammatory response mediated by cytokines at the local and systemic levels in three cases of severe pneumonia caused by Influenza A (H1N1) virus. Methodology: Serum and bronchoalveolar lavage samples were obtained from three mechanically ventilated patients diagnosed with Influenza A (H1N1) virus pneumonia by bronchoscopic bronchoalveolar lavage. Levels of interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrosis factor alpha (TNFα) and interleukin 1 beta (IL-1ß) were meassured in these samples by enzyme-linked immunosorbent assay (ELISA). Results: High levels of C Reactive Protein, Procalcitonin below 1 ng/ml and absence of leukocytosis were common findings in all patients. TNF α and IL-1ß were not detected in the serum. IL-6 levels in serum were (94, pg/ml, 77 pg/ml and 84 pg/ml) respectively in the three patients, while IL-8 levels were (30,2 pg/ml, 128 pg/ml and 40,5 pg/ml). In the BAL samples, only one of the analysed cytokines, IL-1ß was present at detectable levels in two patients (21 pg/ml and 11 pg/ml respectively). Conclusions: Our results support previous findings which suggest that high levels of IL-6 and IL-8 in serum somehow participate in the inflammatory response in severe cases of pandemic influenza pneumonia.

Revisiting steroid treatment for septic shock: molecular actions and clinical effects - a review

Corticosteroids are widely used to treat a diversity of pathological conditions including allergic, autoimmune and some infectious diseases. These drugs have complex mechanisms of action involving both genomic and non-genomic mechanisms and interfere with different signal transduction pathways in the cell. The use of corticosteroids to treat critically ill patients with acute respiratory distress syndrome and severe infections, such as sepsis and pneumonia, is still a matter of intense debate in the scientific and medical community with evidence both for and against its use in these patients. Here, we review the basic molecular mechanisms important for corticosteroid action as well as current evidence for their use, or not, in septic patients. We also present an analysis of the reasons why this is still such a controversial point in the literature.

Intratracheal suctioning in sick preterm infants: prevention of intracranial hypertension and cerebral hypoperfusion by muscle paralysis.

In a prospective nonrandomized study, using each baby as his or her own control, we compared intracranial pressure (anterior fontanel pressure as measured with the Digilab pneumotonometer), cerebral perfusion pressure, BP, heart rate, transcutaneous Po2, and transcutaneous Pco2 before, during, and after endotracheal suctioning, with and without muscle paralysis, in 28 critically ill preterm infants with respiratory distress syndrome. With suctioning, there was a small but significant increase in intracranial pressure in paralyzed patients (from 13.7 [mean] +/- 4.4 mm Hg [SD] to 15.8 +/- 5.2 mm Hg) but a significantly larger (P less than .001) increase when they were not paralyzed (from 12.5 +/- 3.6 to 28.5 +/- 8.3 mm Hg). Suctioning led to a slight increase in BP with (from 45.3 +/- 9.1 to 48.0 +/- 8.7 mm Hg) and without muscle paralysis (from 45.1 +/- 9.4 to 50.0 +/- 11.7 mm Hg); but there was no significant difference between the two groups. The cerebral perfusion pressure in paralyzed infants did not show any significant change before, during, and after suctioning (31.5 +/- 9.1 mm Hg before v 32.0 +/- 8.7 mm Hg during suctioning), but without muscle paralysis cerebral perfusion pressure decreased (P less than .001) from 32.8 +/- 9.7 to 21.3 +/- 13.1 mm Hg. Suctioning induced a slight decrease in mean heart rate and transcutaneous Po2, but pancuronium did not alter these changes. There was no statistical difference in transcutaneous Pco2 before, during, and after suctioning with and without muscle paralysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus SEMICYUC-SENPE: Obese patient

As a response to metabolic stress, obese critically-ill patients have the same risk of nutritional deficiency as the non-obese and can develop protein-energy malnutrition with accelerated loss of muscle mass. The primary aim of nutritional support in these patients should be to minimize loss of lean mass and accurately evaluate energy expenditure. However, routinely used formulae can overestimate calorie requirements if the patient's actual weight is used. Consequently, the use of adjusted or ideal weight is recommended with these formulae, although indirect calorimetry is the method of choice. Controversy surrounds the question of whether a strict nutritional support criterion, adjusted to the patient's requirements, should be applied or whether a certain degree of hyponutrition should be allowed. Current evidence suggested that hypocaloric nutrition can improve results, partly due to a lower rate of infectious complications and better control of hyperglycemia. Therefore, hypocaloric and hyperproteic nutrition, whether enteral or parenteral, should be standard practice in the nutritional support of critically-ill obese patients when not contraindicated. Widely accepted recommendations consist of no more than 60-70% of requirements or administration of 11-14 kcal/kg current body weight/day or 22-25 kcal/kg ideal weight/day, with 2-2.5 g/kg ideal weight/day of proteins. In a broad sense, hypocaloric-hyperprotein regimens can be considered specific to obese critically-ill patients, although the complications related to comorbidities in these patients may require other therapeutic possibilities to be considered, with specific nutrients for hyperglycemia, acute respiratory distress syndrome (ARDS) and sepsis. However, there are no prospective randomized trials with this type of nutrition in this specific population subgroup and the available data are drawn from the general population of critically-ill patients. Consequently, caution should be exercised when interpreting these data.

Mechanical ventilation and clinical practice heterogeneity in intensive care units: a multicenter case-vignette study.

BACKGROUND: Observational studies on mechanical ventilation (MV) show practice variations across ICUs. We sought to determine, with a case-vignette study, the heterogeneity of processes of care in ICUs focusing on mechanical ventilation procedures, and whether organizational patterns or physician characteristics influence practice variations. METHODS: We conducted a cross-sectional multicenter study using the case-vignette methodology. Descriptive analyses were calculated for each organizational pattern and respondent characteristics. An Index of Qualitative Variation (IQV, from 0, no heterogeneity, to a maximum of 1) was calculated. RESULTS: Forty ICUs from France (N = 33) and Switzerland (N = 7) participated; 396 physicians answered our case-vignettes. There was major heterogeneity of management processes related to MV within and across centers (mean IQV per center 0.51, SD 0.09). We observed the lowest variability (mean IQV per question < 0.4) for questions related to intubation procedure, ventilation of acute respiratory distress syndrome and the use of the semirecumbent position. We observed a high variability (mean IQV per question > 0.6) for questions related to management of endotracheal tube or suctioning, management of sedation and analgesia, and respect of autonomy. Heterogeneity was independent of respondent characteristics and of the presence of written procedures. There was a correlation between the processes associated with the highest variability (mean IQV per question > 0.6) and the annual volume of ICU admission (r = 0.32 (0.01 to 0.58)) and MV (r = 0.38 (0.07 to 0.63)). Within ICUs there was a large heterogeneity regarding knowledge of a local written procedure. CONCLUSIONS: Large clinical practice variations were found among ICUs. High volume centers were more likely to have heterogeneous practices. The presence of a local written procedure or respondent characteristics did not influence practice variation.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

OBJECTIVE: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock," published in 2004. DESIGN: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. METHODS: We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. RESULTS: Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). CONCLUSION: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

Effects of paralysis with pancuronium bromide on joint mobility in premature infants.

To study the effects of muscle paralysis on joint mobility, we compared eight premature infants treated with pancuronium bromide with a control group. A significant reduction was observed in hip and knee flexion, and in ankle dorsal extension, which tended to resolve in time. We conclude that muscle paralysis reduces the mobility of selected joints; spontaneous activity appears to prevent long-term contractures.

Surfactant palmitoylmyristoylphosphatidylcholine is a marker for alveolar size during disease.

Two common lung-related complications in the neonate are respiratory distress syndrome, which is associated with a failure to generate low surface tension at the air-liquid interface because of pulmonary surfactant insufficiency, and bronchopulmonary dysplasia (BPD), a chronic lung injury with reduced alveolarization. Surfactant phosphatidylcholine (PC) molecular species composition during alveolarization has not been examined. Mass spectrometry analysis of bronchoalveolar lavage fluid of rodents and humans revealed significant changes in surfactant PC during alveolar development and BPD. In rats, total PC content rose during alveolarization, which was caused by an increase in palmitoylmyristoyl-PC (16:0/14:0PC) concentration. Furthermore, two animal models of BPD exhibited a specific reduction in 16:0/14:0PC content. In humans, 16:0/14:0PC content was specifically decreased in patients with BPD and emphysema compared with patients without alveolar pathology. Palmitoylmyristoyl-PC content increased with increasing intrinsic surfactant curvature, suggesting that it affects surfactant function in the septating lung. The changes in acyl composition of PC were attributed to type II cells producing an altered surfactant during alveolar development. These data are compatible with extracellular surfactant 16:0/14:0PC content being an indicator of alveolar architecture of the lung.

La douleur prolongée chez le nouveau-né: étude de cas [Prolonged pain in neonates: retrospective analysis].

INTRODUCTION: infants hospitalised in neonatology are inevitably exposed to pain repeatedly. Premature infants are particularly vulnerable, because they are hypersensitive to pain and demonstrate diminished behavioural responses to pain. They are therefore at risk of developing short and long-term complications if pain remains untreated. CONTEXT: compared to acute pain, there is limited evidence in the literature on prolonged pain in infants. However, the prevalence is reported between 20 and 40 %. OBJECTIVE : this single case study aimed to identify the bio-contextual characteristics of neonates who experienced prolonged pain. METHODS : this study was carried out in the neonatal unit of a tertiary referral centre in Western Switzerland. A retrospective data analysis of seven infants' profile, who experienced prolonged pain ,was performed using five different data sources. RESULTS : the mean gestational age of the seven infants was 32weeks. The main diagnosis included prematurity and respiratory distress syndrome. The total observations (N=55) showed that the participants had in average 21.8 (SD 6.9) painful procedures that were estimated to be of moderate to severe intensity each day. Out of the 164 recorded pain scores (2.9 pain assessment/day/infant), 14.6 % confirmed acute pain. Out of those experiencing acute pain, analgesia was given in 16.6 % of them and 79.1 % received no analgesia. CONCLUSION: this study highlighted the difficulty in managing pain in neonates who are exposed to numerous painful procedures. Pain in this population remains underevaluated and as a result undertreated.Results of this study showed that nursing documentation related to pain assessment is not systematic.Regular assessment and documentation of acute and prolonged pain are recommended. This could be achieved with clear guidelines on the Assessment Intervention Reassessment (AIR) cyclewith validated measures adapted to neonates. The adequacy of pain assessment is a pre-requisite for appropriate pain relief in neonates.