Alveolar and serum concentrations of imipenem in two lung transplant recipients supported with extracorporeal membrane oxygenation

Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with respiratory failure who fail conventional treatment. Postoperative pneumonia is the most common infection after lung transplantation (40%). Imipenem is frequently used for empirical treatment of nosocomial pneumonia in the intensive care unit. Nevertheless, few data are available on the impact of ECMO on pharmacokinetics, and no data on imipenem dosing during ECMO. Currently, no guidelines exist for antibiotic dosing during ECMO support. We report the cases of 2 patients supported with venovenous ECMO for refractory acute respiratory distress syndrome following single lung transplantation for pulmonary fibrosis, treated empirically with 1 g of imipenem intravenously every 6 h. Enterobacter cloacae was isolated from the respiratory sample of Patient 1 and Klebsiella pneumoniae was isolated from the respiratory sample of Patient 2. Minimum inhibitory concentrations of the 2 isolated strains were 0.125 and 0.25 mg/L, respectively. Both patients were still alive on day 28. This is the first report, to our knowledge, of imipenem concentrations in lung transplantation patients supported with ECMO. This study confirms high variability in imipenem trough concentrations in patients on ECMO and with preserved renal function. An elevated dosing regimen (4 g/24 h) is more likely to optimize drug exposure, and therapeutic drug monitoring is recommended, where available. Population pharmacokinetic studies are indicated to develop evidence‐based dosing guidelines for ECMO patients.     

Severe and multiple hypoglycemic episodes are associated with increased risk of death in ICU patients

IntroductionIn a randomized controlled trial comparing tight glucose control with a computerized decision support system and conventional protocols (post hoc analysis), we tested the hypothesis that hypoglycemia is associated with a poor outcome, even when controlling for initial severity.MethodsWe looked for moderate (2.2 to 3.3 mmol/L) and severe (<2.2 mmol/L) hypoglycemia, multiple hypoglycemic events (n ≥3) and the other main components of glycemic control (mean blood glucose level and blood glucose coefficient of variation (CV)). The primary endpoint was 90-day mortality. We used both a multivariable analysis taking into account only variables observed at admission and a multivariable matching process (greedy matching algorithm; caliper width of 10⁻⁵ digit with no replacement).ResultsA total of 2,601 patients were analyzed and divided into three groups: no hypoglycemia (n =1,474), moderate hypoglycemia (n =874, 34%) and severe hypoglycemia (n =253, 10%). Patients with moderate or severe hypoglycemia had a poorer prognosis, as shown by a higher mortality rate (36% and 54%, respectively, vs. 28%) and decreased number of treatment-free days. In the multivariable analysis, severe (odds ratio (OR), 1.50; 95% CI, 1.36 to 1.56; P =0.043) and multiple hypoglycemic events (OR, 1.76, 95% CI, 1.31 to 3.37; P <0.001) were significantly associated with mortality, whereas blood glucose CV was not. Using multivariable matching, patients with severe (53% vs. 35%; P <0.001), moderate (33% vs. 27%; P =0.029) and multiple hypoglycemic events (46% vs. 32%, P <0.001) had a higher 90-day mortality.ConclusionIn a large cohort of ICU patients, severe hypoglycemia and multiple hypoglycemic events were associated with increased 90-day mortality.

Trial registration

Clinicaltrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT01002482","term_id":"NCT01002482"}}NCT01002482. Registered 26 October 2009.     

18F]-FDG positron imaging in clinical management of lymphoma patients

[18F]-FDG is a glucose analogue labelled with a short-lived positron emitter. During the past decade, it has been proposed to detect in vivo lymphoma lesions with PET, a new non-invasive imaging modality. We aimed at reviewing the current experience with FDG in several clinical settings of lymphoma. Due to the lack of specificity of FDG for lymphoma, histology remains compulsory to establish the diagnosis. Nevertheless, in the case of AIDS, FDG imaging has been proposed to differentiate lymphoma and opportunistic infections in brain lesions. To explore lymphoma extension, FDG-PET highlights more lesions than CT or the clinical examination and results in upstaging 13% of cases. It could also be used for selecting a site for biopsy when the location considered first clinically is difficult to access. Staging lymphoma with FDG-PET also provides baseline images for subsequent evaluation of therapy, which is one of the most promising indications: a negative scan predicts response to therapy and subsequent remission with a predictive value of 89%, and a positive scan either reflects resistance or predicts relapse with a predictive value of 83%. The current achievement of FDG imaging is the early detection of recurrence or of viable tissue in residual masses that remain several months after treatment. Both its sensitivity (84%) and its specificity (95%) overwhelm the values of conventional imaging, mainly CT and gallium-67 scintigraphy. When PET, as a new clinical imaging modality, is not yet widely demanded by clinicians and/or the number of FDG examinations is less than 500 per year, a 'hybrid' gamma-camera or CDET can be an alternative to dedicated PET. For 3 years, we have been using FDG-CDET in the 2D mode without attenuation correction, and obtained the following accuracy in a total of 40 examinations that could be evaluated: 85% for assessment of chemotherapy and 92% to detect recurrences and evaluate residual masses. Our preliminary results also stress the interest in FDG examination in childhood lymphoma, with the same indications as in adults.     

Candida and severe acute pancreatitis: We won't be fooled again

Several studies have suggested a role of candida in infected cases of severe acute pancreatitis. This commentary reports high incidence and mortality rates of candida infection in this setting and demonstrates the value of the colonization index to detect patients at risk for fungal infection. These findings indicate the need to review the place of antifungal therapy and prophylaxis.     

Utility of thallium-201 and iodine-123 metaiodobenzylguanidine in the scintigraphic detection of neuroendocrine neoplasia

Metaiodobenzylguanidine (MIBG) is a specific marker for neuroendocrine tumours, such as phaeochromocytoma, neuroblastoma, medullary thyroid cancer (MTC) and paraganglioma, but it suffers in some cases (especially in MTC) from a lack of sensitivity. Thallium is a well-known marker of cellularity with a great sensitivity and a lack of specificity. In order to determine whether the association of these two markers is able to improve the detection of neuroendocrine lesions, 137 scintigraphic examinations using MIBG and thallium were performed in 101 patients referred for suspicion or follow-up of neuroendocrine tumours. Thallium chloride was first injected (1 MBq/kg), images being acquired about 20 min after injection; ¹²³I-MIBG (4 MBq/kg) was then injected and images acquired 5 and 24 h later. In patients with phaeochromocytoma or neuroblastoma, thallium scintigraphy appeared of little help since no tumoural site was discovered by thallium accumulation alone. In contrast, thallium examination seemed of interest in the detection of paraganglioma and MTC, the association of the two radiopharmaceuticals increasing the number of detected sites.     

Clinical consequences of resistant Candida infections in intensive care

Many issues need to be addressed by the Intensive Care Unit physician in the decision-making process regarding antifungal therapy for Candida infection, most importantly pharmacokinetic concerns and/or organ failure limitations. In addition, the extensive use of antifungal agents can select for Candida spp. that exhibit decreased susceptibility to these agents. However, the risk appears low, even in the case of prophylactic or pre-emptive antifungal therapy, but this needs to be confirmed in large-scale studies.     

Activated proteine C

Recombinant human activated protein C (APC) might be the first pharmacological intervention which decreases mortality in the course of severe sepsis. Surviving Sepsis Campaign guidelines have recommended the use of APC with grade B level of proof. During sepsis, the APC pathway serves as a major system for controlling thrombosis inhibiting thrombin formation, limiting inflammatory responses, and potentially decreasing endothelial cell apoptosis. APC use was assessed in the course of severe sepsis 24 microg/kg/h for 96 hours with the aim of inhibiting coagulopathy and inflammation. The PROWESS trial included 1,690 patients and demonstrated a significantly decreased mortality in the treated group. Additional publications have clarified the characteristics of the included patients and tried to outline the potential benefits of APC. The results of ENHANCE, a multicenter open trial, have confirmed the trends reported in the PROWESS trial. Evidence supporting the efficacy of APC in the management of severe sepsis is clearly assessed. However, several issues remain unsolved and require to be addressed as the appropriate use of the drug and its place with other adjunctive therapies directed the sepsis process.