O. Fourcade

Central venous-to-arterial carbon dioxide difference: an additional target for goal-directed therapy in septic shock?

ObjectiveTo test the hypothesis that, in resuscitated septic shock patients, central venous-to-arterial carbon dioxide difference [P(cv-a)CO2] may serve as a global index of tissue perfusion when the central venous oxygen saturation (ScvO2) goal value has already been reached.DesignProspective observational study.SettingA 22-bed intensive care unit (ICU).PatientsAfter early resuscitation in the emergency unit, 50 consecutive septic shock patients with ScvO2xa0>xa070% were included immediately after their admission into the ICU (T0). Patients were separated in Low P(cv-a)CO2 group (Low gap; nxa0=xa026) and High P(cv-a)CO2 group (High gap; nxa0=xa024) according to a threshold of 6xa0mmHg at T0.MeasurementsMeasurements were performed every 6 h over 12 h (T0, T6, T12).ResultsAt T0, there was a significant difference between Low gap patients and High gap patients for cardiac index (CI) (4.3xa0±xa01.6 vs. 2.7xa0±xa00.8xa0l/min/m², Pxa0<xa00.0001) but not for ScvO2 values (78xa0±xa05 vs. 75xa0±xa05%, Pxa0=xa00.07). From T0 to T12, the clearance of lactate was significantly larger for the Low gap group than for the High gap group (Pxa0<xa00.05) as well as the decrease of SOFA score at T24 (Pxa0<xa00.01). At T0, T6 and T12, CI and P(cv-a)CO2 values were inversely correlated (Pxa0<xa00.0001).ConclusionIn ICU-resuscitated patients, targeting only ScvO2 may not be sufficient to guide therapy. When the 70% ScvO2 goal-value is reached, the presence of a P(cv-a)CO2 larger than 6xa0mmHg might be a useful tool to identify patients who still remain inadequately resuscitated.

Lysophosphatidic acid as a phospholipid mediator: pathways of synthesis

From very recent studies, including molecular cloning of cDNA coding for membrane receptors, lysophosphatidic acid (LPA) reached the status of a novel phospholipid mediator with various biological activities. Another strong argument supporting this view was the discovery that LPA is secreted from activated platelets, resulting in its appearance in serum upon blood coagulation. The metabolic pathways as well as the enzymes responsible for LPA production are poorly characterized. However, a survey of literature data indicates some interesting issues which might be used as the basis for further molecular characterization of phospholipases A able to degrade phosphatidic acid.

Pulse pressure variations adjusted by alveolar driving pressure to assess fluid responsiveness

ObjectiveTo evaluate the ability of ∆PP/∆P [pulse pressure variations (∆PP) adjusted by alveolar pressure variations (∆Pxa0=xa0Pplat-PEEPtot)] in predicting fluid responsiveness, to compare its accuracy to that of ∆PP used alone and to evaluate the influence of tidal volume (Vt) on these two indices.DesignProspective study.SettingA 22-bed general intensive care unit (ICU).PatientsEighty-four surgical or medical ventilated patients requiring fluid challenge.InterventionA 6xa0ml/kg colloid fluid challenge in 30xa0min.Measurements and resultsHemodynamic measurements taken before and after fluid challenge. Patients separated into responders and nonresponders according to a 15% increase in their cardiac output. Thirty-nine patients found to be responders and 45 nonresponders. ∆PP/∆P and ∆PP were both higher in responders than in nonresponders. ∆PP/∆P was a better predictor of fluid responsiveness than ∆PP, especially for patients ventilated with Vtxa0≥xa08xa0ml/kg [area under the curve (AUC) 0.88 (0.77–0.98) versus 0.75 (0.60–0.89), Pxa0<xa00.01)]. In this population ∆PP/∆P higher than 0.9 predicted fluid response with positive predictive value of 87% and negative predictive value of 78%. Overall ∆PP and ∆PP/∆P reliability was poor for patients ventilated with Vtxa0<xa08xa0ml/kg [AUC 0.63 (0.45–0.81) and 0.72 (0.55–0.88), respectively].ConclusionIn this mixed ICU population ∆PP adjusted by ∆P is a simple index which outperforms ∆PP for patients ventilated with Vtxa0≥xa08xa0ml/kg. However, correcting ∆PP by ∆P still fails to predict fluid response reliably in patients ventilated with low tidal volume.

Usefulness of Cardiothoracic Chest Ultrasound in the Management of Acute Respiratory Failure in Critical Care Practice

BACKGROUNDnThis study investigated the clinical relevance of early general chest ultrasonography (ie, heart and lung recordings) in patients in the ICU with acute respiratory failure (ARF).nnnMETHODSnWe prospectively compared this diagnostic approach (ultrasound) to a routine evaluation established from clinical, radiologic, and biologic data (standard). Subjects were patients consecutively admitted to the ICU of a university teaching hospital during a 1-year period. Inclusion criteria were age ≥ 18 years and the presence of severe ARF criteria to justify ICU admission. We compared the diagnostic approaches and the final diagnosis determined by a panel of experts.nnnRESULTSnSeventy-eight patients were included (age, 70 ± 18 years; sex ratio, 1). Three patients given two or more simultaneous diagnoses were subsequently excluded. The ultrasound approach was more accurate than the standard approach (83% vs 63%, respectively; P < .02). Receiver operating characteristic curve analysis showed greater diagnostic performance of ultrasound in cases of pneumonia (standard, 0.74 ± 0.12; ultrasound, 0.87 ± 0.14; P < .02), acute hemodynamic pulmonary edema (standard, 0.79 ± 0.11; ultrasound, 0.93 ± 0.08; P < .007), decompensated COPD (standard, 0.8 ± 0.09; ultrasound, 0.92 ± 0.15; P < .05), and pulmonary embolism (standard, 0.65 ± 0.12; ultrasound, 0.81 ± 0.17; P < .04). Furthermore, we found that the use of ultrasound data could have significantly improved the initial treatment.nnnCONCLUSIONSnThe use of cardiothoracic ultrasound appears to be an attractive complementary diagnostic tool and seems able to contribute to an early therapeutic decision based on reproducible physiopathologic data.

Membrane sidedness of biosynthetic pathways involved in the production of lysophosphatidic acid

Lysophosphatidic acid (LPA) is a novel phospholipid mediator with diverse biological activities such as smooth muscle contraction, and proliferative effects or modifications of cytoskeleton. Activated blood platelets are the best identified source, explaining accumulation of LPA in serum upon blood coagulation. However, the metabolic pathways responsible for LPA synthesis are still poorly known. Using a model of human erythrocytes treated with the calcium ionophore A23187, we have shown that type II secretory phospholipase A2 (sPLA2) is able to produce LPA by hydrolyzing phosphatidic acid exposed on the cell surface after phospholipid scrambling. A similar mechanism does not appear to occur in platelets, where inhibitors of sPLA2 or genetic lack of the enzyme do not modify LPA production. However, this does not definitely eliminate the possibility that LPA is also produced in platelets in the external leaflet of the membrane by other phospholipases, which have to be better characterized.

Guidewire localization by transthoracic echocardiography during central venous catheter insertion: a periprocedural method to evaluate catheter placement

PurposeTo evaluate the feasibility of guidewire detection in right cardiac cavities by transthoracic echocardiography (TTE) in order to detect catheter misplacement and to optimize central venous catheter (CVC) positioning. Ultrasonic control for catheter tip positioning was compared to that by chest X-ray (CXR).MethodsWe conducted a monocentric prospective observational study (January–November 2010). All consecutive patients undergoing CVC insertion were included. The puncture was performed using the landmark method or ultrasound guidance. TTE was performed during the procedure to follow the arrival of the guidewire in the right cardiac cavities. Catheter misplacement was defined as an aberrant position on the postprocedural CXR (catheter positioning in ipsilateral or contralateral veins). The primary endpoint was the prediction of catheter misplacement by guidewire detection in the cardiac cavities. The secondary endpoint was the optimization of the catheter tip placement in the superior vena cava.ResultsA total of 98 patients received 101 CVC. The guidewire was visualized in 92 cases. In five cases, the guidewire was not seen in the right cardiac cavities and CXR showed catheter misplacement. In four cases, poor echogenicity led to the ultrasound examination being abandoned. Catheter misplacement was detected by TTE with a sensitivity of 96xa0% (CI 90–98xa0%), a specificity of 83xa0% (CI 44–97xa0%), a positive predictive value of 98xa0%, and a negative predictive value of 55xa0%. Likelihood ratios were LR+ 5.7 (CI 0.96–34.4) and LR− 0.05 (CI 0.02–0.14). Guidewire removal under TTE avoided an excessively distal position of the catheter tip in all cases.ConclusionTTE is a reliable tool to detect catheter misplacement and to optimize catheter tip positioning during the procedure of CVC insertion.

Postoperative myocardial damages after hip fracture repair are frequent and associated with a poor cardiac outcome: a three-hospital study

8. Kaiser C, Kuster GM, Erne P et al. Risks and benefits of optimised medical and revascularisation therapy in elderly patients with anginaon-treatment analysis of the TIME trial. Eur Heart J 2004; 25: 1036–42. 9. Claude J, Schindler C, Kuster GM et al. Cost-effectiveness of invasive versus medical management of elderly patients with chronic symptomatic coronary artery disease. Eur Heart J 2004; 25: 2195–203. 10. Stone PH, Thompson B, Anderson V et al. Influence of race, sex, and age on management of unstable angina and non-Q wave myocardial infarction. The TIMI-III registry. JAMA 1996; 275: 1104–12. 11. Collinson J, Flather MD, Fox KAA et al. Clinical outcomes, risk stratification and practice patterns of unstable angina and myocardial infarction without ST elevation: prospective registry of acute ischaemic syndromes in the UK (PRAIS-UK). Eur Heart J 2000; 21: 1450–57. 12. De Gregorio J, Kobayashi Y, Albiero R et al. Coronary artery stenting in the elderly: short-term outcome and long-term angiographic and clinical follow up. J Am Coll Cardiol 1998; 32: 577–83. 13. Maurer MS. Age: a nonmodifiable risk factor? J Coll Cardiol 2003; 42: 1427–8. 14. Bowling A. Ageism in cardiology. BMJ 1999; 319: 1353–5. 15. Graham MM, Ghali WA, Faris PD et al. Survival after coronary revascularisation in the elderly. Circulation 2002; 105: 2378–84. 16. Floyd KC, Jayne JE, Kaplan AV et al. Age-based differences of percutaneous intervention in the drug-eluting stent era. J Interven Cardiol 2006; 19: 381–7. 17. Spertus JA, Kettelkamp R, Vance C et al. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement. Circulation 2006; 113: 2803–9.

New developments in phospholipase A2

Some of the most recent data concerning various phospholipases A2, with special emphasis on secretory, cytosolic, and calcium-independent phospholipases A2 are summarized. Besides their contribution to the production of proinflammatory lipid mediators, the involvement of these enzymes in key cell responses such as apoptosis or tumor cell metastatic potential is also discussed, taking advantage of transgenic models based on gene invalidation by homologous recombination. The possible role of secretory and cytosolic platelet-activating factor acetyl hydrolases is also briefly mentioned. Finally, the ectopic expression in epididymis of an intestinal phospholipase B opens some novel issues as to the possible function of phospholipases in reproduction.

Relative accuracy of arterial and capillary glucose meter measurements in critically ill patients

AIMnAs optimizing glucose control in critically ill patients remains a challenge for intensive-care physicians, this study aimed to determine the accuracy of glucose measurements.nnnMETHODSnThe accuracy of capillary and arterial blood glucose meter measurements was compared with central laboratory arterial glucose measurements; the factors associated with inaccurate measures were also determined.nnnRESULTSnAltogether, 302 samples from 75 patients were assessed. Mean glucose levels were 126±52 mg/dL for capillary measurements, 133±50 mg/dL for arterial measurements and 143±54 mg/dL for serum glucose laboratory measurements. Compliance with the ISO 15197 guidelines was observed in 74.8% of the capillary samples and 88.7% of the arterial samples. However, all measurements by glucose meter (with either capillary or arterial samples) led to underestimations of serum glucose.nnnCONCLUSIONnIn critically ill patients, glucose measurements from capillary and arterial blood by glucose meter are inaccurate, and can potentially lead to inappropriate use of insulin-infusion protocols and failure to achieve glycaemic targets.

An unusual cause of severe lactic acidosis: cyanide poisoning after bitter almond ingestion

Dear Editor, Although cyanide exists in various alimentary sources like manioc, corn, bitter almonds, peach or apricot kernels, food-related cyanide intoxications are rare [1]. A 58-year-old healthy woman was admitted for sudden headaches, dizziness, vomiting, and generalized seizures. Prehospital medical services found her comatose (Glasgow Coma Score: 5) with bradycardia (30/min) and nonmeasurable blood pressure. She was promptly intubated and received fluids. A brain CT scan was normal. On intensive care unit (ICU) admission, her blood pressure was 80/40 mmHg, heart rate 62/min, SpO2 100% (FiO2: 100%), and temperature 37.0 C. Physical examination, electrocardiogram, and echocardiography were unremarkable. Severe lactic acidosis (arterial pH: 6.59, base deficit: 36.0 mmol/l, anion gap: 33.0 mmol/l, and plasma lactate concentration: 26.0 mmol/l) was assessed without ketosis, osmolar gap, liver or renal dysfunction. Fluids (2,000 ml), norepinephrine (0.5 mg/h), insulin, and sodium bicarbonate were infused. Routine toxicological screening was negative. Blood cyanide concentration was 2.77 mg/l (spectrophotometric method; N 0.2 mg/l; limit of detection: 0.06 mg/l) 6 h after coma onset. Hydroxocobalamin (10 g, 140 mg/kg) was immediately infused, resulting in complete recovery: lactate normalization (within 12 h, Table 1), norepinephrine weaning (20 h), acid/base balance correction (36 h), extubation (day 2), and ICU discharge (day 3). Her husband finally remembered that she had ingested a large quantity of bitter almonds (around 50) from the garden, 2 h before symptom onset. Accidental food-related cyanide poisonings are unusual [1]. Signs are delayed after ingestion, in relation to enzymatic processes producing cyanide in the gut from the ingested cyanogenic glucosides. Cyanide poisoning is rapidly fatal if not promptly treated. Clinical features are not specific, misleading the diagnosis. However, when suspicion is based on compatible circumstances, plasma lactate concentrations C8 mmol/l are an excellent predictor of blood cyanide concentrations C1 mg/l [2]. In our case, despite no relevant anamnesis, cyanide poisoning was suspected because of severe lactic acidosis with coma, hypotension, and bradycardia in the absence of sepsis. Reported symptoms of cyanide poisoning following almond/seed ingestion included headaches, dizziness, sweating, pink cyanosis, coma, seizures, hyperthermia, hypotension, polypnea, bradypnea, hypoglycemia, and lactic acidosis [3, 4]. To our knowledge, hyperlactatemia (pH 7.17, lactate: 14.3 mmol/l) was reported in only one case after ingestion of bitter almonds with laetrile tablets (containing amygdaline) given for alternative cancer treatment [3]. The present case is unique for two reasons: the severity of almondinduced lactic acidosis and its dramatic improvement after hydroxocobalamin infusion. Management of cyanide poisoning is based on advanced life support and antidotes. Despite cyanide-induced deficient cell oxygen utilization, increased oxygen delivery (FiO2: 100%) is useful to reactivate mitochondrial enzymes and other oxidative systems. Hydroxocobalamin is an effective and safe antidote binding cyanide on an equimolar ratio to form stable cyanocobalamin, which is excreted in urine [5]. Although we should