Charikleia S. Vrettou

Factor XIII deficiency as a potential cause of supratentorial haemorrhage after posterior fossa surgery

BackgroundPostoperative intracranial haemorrhage can be a dramatic event, carrying significant morbidity and mortality. Bleeding at sites remote from the operation area represents a small percentage of haemorrhages whose aetiology remains unclear (Harders et al. Acta Neurochir (Wien) 74(1-2):57–60, 1985).AimWe present the case of a 60-year-old patient who underwent posterior fossa craniotomy for the removal of a space-occupying lesion and suffered supratentorial haemorrhage soon after the operation.ResultsA thorough postoperative investigation revealed low levels of factor XIII (FXIII), the factor mainly responsible for fibrin clot stabilisation.ConclusionWe suggest that reduced FXIII activity may be an important but preventable predisposing factor to remote postoperative haemorrhage in neurosurgical patients.

High-frequency oscillation and tracheal gas insufflation in patients with severe acute respiratory distress syndrome and traumatic brain injury: an interventional physiological study

IntroductionIn acute respiratory distress syndrome (ARDS), combined high-frequency oscillation (HFO) and tracheal gas insufflation (TGI) improves gas exchange compared with conventional mechanical ventilation (CMV). We evaluated the effect of HFO-TGI on PaO2/fractional inspired O2 (FiO2) and PaCO2, systemic hemodynamics, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) in patients with traumatic brain injury (TBI) and concurrent severe ARDS.MethodsWe studied 13 TBI/ARDS patients requiring anesthesia, hyperosmolar therapy, and ventilation with moderate-to-high CMV-tidal volumes for ICP control. Patients had PaO2/FiO2 <100 mm Hg at end-expiratory pressure ≥10 cm H2O. Patients received consecutive, daily, 12-hour rescue sessions of HFO-TGI interspersed with 12-hour periods of CMV. HFO-TGI was discontinued when the post-HFO-TGI PaO2/FiO2 exceeded 100 mm Hg for >12 hours. Arterial/central-venous blood gases, hemodynamics, and ICP were recorded before, during (every 4 hours), and after HFO-TGI, and were analyzed by using repeated measures analysis of variance. Respiratory mechanics were assessed before and after HFO-TGI.ResultsEach patient received three to four HFO-TGI sessions (total sessions, n = 43). Pre-HFO-TGI PaO2/FiO2 (mean ± standard deviation (SD): 83.2 ± 15.5 mm Hg) increased on average by approximately 130% to163% during HFO-TGI (P < 0.01) and remained improved by approximately 73% after HFO-TGI (P < 0.01). Pre-HFO-TGI CMV plateau pressure (30.4 ± 4.5 cm H2O) and respiratory compliance (37.8 ± 9.2 ml/cm H2O), respectively, improved on average by approximately 7.5% and 20% after HFO-TGI (P < 0.01 for both). During HFO-TGI, systemic hemodynamics remained unchanged. Transient improvements were observed after 4 hours of HFO-TGI versus pre-HFO-TGI CMV in PaCO2 (37.7 ± 9.9 versus 41.2 ± 10.8 mm Hg; P < 0.01), ICP (17.2 ± 5.4 versus 19.7 ± 5.9 mm Hg; P < 0.05), and CPP (77.2 ± 14.6 versus 71.9 ± 14.8 mm Hg; P < 0.05).ConclusionsIn TBI/ARDS patients, HFO-TGI may improve oxygenation and respiratory mechanics, without adversely affecting PaCO2, hemodynamics, or ICP. These findings support the use of HFO-TGI as a rescue ventilatory strategy in patients with severe TBI and imminent oxygenation failure due to severe ARDS.

MELAS syndrome diagnosed in ICU in a 56-year-old patient presenting with status epilepticus.

The differential diagnosis of stroke in a middle-aged adult usually does not include the mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes syndrome (MELAS), because such a manifestation very rarely first occurs after the age of 40 [1, 2]. We report the case of a 56-year-old woman, brought to our hospital with irritability, aphasia, and ataxic gait. A brain computed tomography revealed a hypodense area on the left temporal lobe (Fig. 1). Ten hours later she developed convulsive status epilepticus and loss of consciousness. She was treated with phenytoin and transferred to the ICU, mechanically ventilated and sedated with propofol. Her past medical history was marked for a hearing deficit, for which a cochlear implant had been inserted 2 years earlier, and for an episode of loss of consciousness 6 months earlier. She was functional with daily activities. The patient was childless. Three out of her four sisters had died at early age. On ICU admission, physical examination revealed right hemiparesis. Pupils were equal and reactive and vital signs were within normal range. Fundoscopic examination was normal. Laboratory parameters were unremarkable, with the exception of white-cell count 18,900/mm (85 % neutrophils), aspartate aminotransferase 274 U/L, alanine aminotransferase 82 U/L, creatine kinase 9,705 U/L and lactate 3.3 mmol/L. Cerebrospinal fluid (CSF) examination was normal. The electroencephalogram showed frequent temporal spikes and slow wave complexes. Extensive imaging for brain vascular disease and laboratory investigation for autoimmune or infectious brain disease all proved negative. Magnetic resonance imaging was avoided due to the presence of the cochlear implant. On ICU day 7, the patient remained comatose. Persistent elevated blood lactate (2.5–5.3 mmol/L) was noted, despite clinical absence of seizures or haemodynamic instability. Repeat CSF revealed lactate 4.3 mmol/ L, not measured in the first sample. A mitochondrial encephalopathy was then suspected. A quadriceps muscle biopsy specimen revealed ‘‘ragged red fibres’’, corroborating the diagnosis of MELAS. Relatives declined further investigation with mitochondrial DNA analysis because the result would not affect the patient’s management, and there was no reason for genetic counseling. The patient had a slow neurological improvement; she weaned from mechanical ventilation and 44 days after ICU admission she was transferred to a rehabilitation center with a Glasgow Coma Scale of 13. First described in 1984, MELAS is a rare, maternally inherited clinical entity resulting from mutations in the mitochondrial DNA [1, 2]. The term ‘‘strokelike’’ refers to clinical and radiological impression of brain ischemia, albeit not conformed to a vascular territory. Although their pathogenesis remains unclear, relative deficiency of cellular adenosine triphoshate has been implicated [3]. According to diagnostic criteria, ‘‘strokelike’’ episodes have to appear before the age of 40 [2]. Few cases occur after the age of 50 [2–5] and none was first diagnosed in the ICU setting. Partial and complex partial status epilepticus are more commonly seen than generalized convulsive status epilepticus in MELAS [6]. ICU

Comparative evaluation of Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scoring systems in patients admitted to the cardiac intensive care unit.

PURPOSE To assess and compare the performance of Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores in the cardiac intensive care unit (CICU). METHODS A single-center, prospective cohort study in a CICU admitting patients with acute cardiovascular diseases was conducted. Both APACHE II and SOFA were calculated on admission. The area under the receiver operating characteristic curve (AUC) was used to evaluate the discriminative ability for predicting CICU survival, hospital survival, and survival 6 months after hospital discharge. Goodness of fit was assessed using the Hosmer-Lemeshow and the Brier scores. All analyses were conducted separately for the patients with acute coronary syndrome. RESULTS Of the 300 consecutively admitted patients, 206 had acute coronary syndrome. Both scores exhibited good discriminative ability (AUC range, 0.84-0.92), and their AUCs did not differ significantly. The Hosmer-Lemeshow test P values were numerically higher (.151-.949 vs .033-.531), and the Brier score closer to zero (0.0864-0.1570 vs 0.1039-0.1264) for APACHE II compared with SOFA score models. The Acute Physiology and Chronic Health Evaluation was the best single risk factor for CICU mortality (odds ratio, 1.24; 95% confidence interval, 1.13-1.37; P < .001). CONCLUSION Both APACHE II and SOFA scores have good and comparable discriminative ability for predicting outcome. Calibration and accuracy indices are superior for APACHE II.

Meta-analysis of High-frequency Oscillation in Acute Respiratory Distress Syndrome and Accuracy of Results

To the Editor: We read with interest the recent meta-analysis of Maitra et al.,1 which included our randomized clinical study of intermittent recruitment with combined high-frequency oscillation (HFO) and tracheal gas insufflations (TGIs) in severe acute respiratory distress syndrome.2 As clearly mentioned/ described in the Abstract and Results sections of our article,2 and pages 7 and 8 of the Supplement2 (eMethods section), our study was conducted in two periods (first period, n = 54; second period, n = 71; total participants, n = 125), primarily for reasons of feasibility; the study protocol can be accessed through the webpage of our hospital’s scientific society.3 As also (again) clearly stated in the Acknowledgments section of our article,2 the results of our study’s first period were partly presented in international congresses and published in abstract form and also summarized in the preceding HFO meta-analysis of Sud et al.4 In the main analysis with respect to mortality presented in figure 3, Maitra et al.1 included the results of the first period (n = 54; control, n = 27) as reported in the meta-analysis of Sud et al.4 in addition to the results of the whole study (corresponding to both study periods, n = 125; control, n = 64).2 This inevitably resulted in a duplicate inclusion of the results of the first period. Furthermore, first period results do not correspond to reference 25 of the article by Maitra et al.1 The cited article reports the results of our prior physiological study that compared the short-term gas exchange and hemodynamic effects of HFO-TGI, standard HFO, and lungprotective conventional mechanical ventilation.5 This study included 14 patients as also correctly reported in table 2 of the article by Maitra et al.,1 thereby contrasting the wrong number of 54 patients reported in figure 3. An additional, potential source of inaccuracy pertains to the inclusion of the study of Demory et al.1,6 This study had physiological endpoints and reported solely on intensive care unit (ICU) mortality, which does not necessarily coincide with either 30-day or in-hospital mortality.2 Consequently, the actual primary outcome of the meta-analysis was “30-day, or ICU, or in-hospital mortality” and not “30-day, or in-hospital mortality.” Lastly, another point requiring correction was that the 30-day mortality rate of the HFO arm of the study of Young et al.7 was 166 of 398 and not 165 of 398 as reported in figure 3 in the article by Maitra et al.1 A corrected forest plot of 30-day, or ICU, or in-hospital mortality is presented in figure 1. Notably, the pooled risk ratio is quite close to that reported by Maitra et al.1 However, the 95% CI and the I2 value differ, and additional data corrections, including the elimination of the above-mentioned first period2 data duplication, are required in figures 4, 6, and 7.1 In addition, the refractory hypoxemia rates reported by Maitra et al. in figure 8 are again inaccurate with respect to our study.2 Indeed, refractory hypoxemia (as defined in the first paragraph of page 7 of the Supplement2) occurred in one patient of the HFO-TGI group (third paragraph of page 13 and eTable 11 of the Supplement2) and four patients of the control group (subsection Rescue Oxygenation Therapies of page 14 and eTable 11 of the Supplement2). An additional, controversial issue pertains to the inclusion of our study.1,2 This contrasts the study selections of the authors of another two, very recently published, meta-analyses of HFO in acute respiratory distress syndrome.8,9 The HFO treatment we used had substantial differences from the HFO treatments of other clinical studies.7,10–13 These studies used continuous, standard HFO, without a mandatory cuff leak or TGI, as a lung-protective ventilatory strategy.7,10–13 In contrast, we applied intermittent, low-frequency HFO with short-lasting (i.e., approximately 40 s) recruitment maneuvers, a tracheal tube cuff leak, and superimposed TGI as a lung recruitment protocol that was repeated daily for an average of 11.2 h. HFO-TGI was used according to prespecified oxygenation criteria for a median (interquartile range) of 4 days (2 to 5 days) during the first 10 days postrandomization.2 The HFO-TGI recruitment strategy was aimed at reducing the ventilation pressures of the subsequent conventional mechanical ventilation and thus render it less traumatic to the lungs.2,14 The potential advantages of the HFO-TGI strategy relative to other HFO strategies, especially with respect to carbon dioxide elimination and hemodynamics, are shown and discussed in detail elsewhere.10,14 A major advantage of meta-analyses is the reliable comparison of treatment effects, achieved mainly through a large, pooled sample size. This leads to improved external validity relative to included, independent studies, and generalizable results. Although it is perfectly understandable that errors can occur, the pooled results of meta-analyses must be accurate, and this can only be ensured through their repeated checking and verification before publication. Also, studies with methodologies exhibiting unique characteristics and clinical targets2 should be considered for inclusion mainly in sensitivity rather than in primary analyses to prevent potentially excessive increases in the heterogeneity of the pooled results (fig. 1).

Exposure to Stress-Dose Steroids and Lethal Septic Shock After In-Hospital Cardiac Arrest: Individual Patient Data Reanalysis of Two Prior Randomized Clinical Trials that Evaluated the Vasopressin–Steroids–Epinephrine Combination Versus Epinephrine Alone

PurposeLow-dose steroids may reduce the mortality of severely ill patients with septic shock. We sought to determine whether exposure to stress-dose steroids during and/or after cardiopulmonary resuscitation is associated with reduced risk of death due to postresuscitation septic shock.MethodsWe analyzed pooled, individual patient data from two prior, randomized clinical trials (RCTs). RCTs evaluated vasopressin, steroids, and epinephrine (VSE) during resuscitation and stress-dose steroids after resuscitation in vasopressor-requiring, in-hospital cardiac arrest. In the second RCT, 15 control group patients received open-label, stress-dose steroids. Patients with postresuscitation shock were assigned to a Steroids (n = 118) or No Steroids (n = 73) group according to an “as-treated” principle. We used cumulative incidence competing risks Cox regression to determine cause-specific hazard ratios (CSHRs) for pre-specified predictors of lethal septic shock (primary outcome). In sensitivity analyses, data were analyzed according to the intention-to-treat (ITT) principle (VSE group, n = 103; control group, n = 88).ResultsLethal septic shock was less likely in Steroids versus No Steroids group, CSHR, 0.40, 95% confidence interval (CI), 0.20–0.82; p = 0.012. ITT analysis yielded similar results: VSE versus Control, CSHR, 0.44, 95% CI, 0.23–0.87; p = 0.019. Adjustment for significant, between-group baseline differences in composite cardiac arrest causes such as “hypotension and/or myocardial ischemia” did not appreciably affect the aforementioned CSHRs.ConclusionsIn this reanalysis, exposure to stress-dose steroids (primarily in the context of a combined VSE intervention) was associated with lower risk of postresuscitation lethal septic shock.

Ventilation Strategies: High-Frequency Oscillatory Ventilation

High-frequency oscillatory ventilation (HFOV) comprises superimposition of pressure oscillations on a continuous positive airway pressure, termed mean airway pressure. Administered tidal volumes (usual range, 40–210 mL) depend on oscillation frequency (usual range, 3.5–10 Hz) and oscillatory pressure amplitude. Theoretically, HFOV is ideal for lung protection in the acute respiratory distress syndrome (ARDS), as it may minimize the risk of volutrauma and atelectrauma. Prior laboratory studies and the pooled results of prior, small randomized controlled trials (RCTs) of HFOV vs. conventional ventilation (CV) in ARDS were suggestive of an HFOV-associated mortality benefit. However, this hypothesis was refuted by the results of two recent large RCTs of HFOV vs. lung-protective CV. The one RCT reported no difference in mortality between treatment arms, whereas the other RCT reported an HFOV-associated harm. The latter result could be partly due to HFOV-induced dysfunction of the right ventricle (RV). In the present chapter, we provide a brief summary of the mechanisms of gas exchange during HFOV and then review published physiological and RCT data, in order to provide a rationale for selecting HFOV settings so as to achieve both lung and RV protection. In this context, we also review available data on the combination of HFOV with tracheal gas insufflation (TGI) and attempt to establish a background for future clinical research involving lung and RV protective HFOV with or without TGI. Future research could also evaluate combination treatments such as prone, lung-protective CV interspersed with supine HFOV.

Letter by Mentzelopoulos et al Regarding Article “β-Adrenergic Receptor–Mediated Cardiac Contractility Is Inhibited Via Vasopressin Type 1A-Receptor–Dependent Signaling”

In patients with cardiac arrest, the adverse effects of epinephrine stimulation of β-adrenergic receptors (βARs) may include increased myocardial oxygen consumption, deranged myocardial oxygen demand-to-availability balance, cardiomyocyte contraction band necrosis, and postresuscitation arrhythmias and myocardial dysfunction. Tilley et al1 recently showed that vasopressin stimulation of cardiomyocyte vasopressin type 1A receptors triggers a G protein–related kinase-dependent, acute desensitization of βARs, with …

Vasopressin versus terlipressin and low-dose versus high-dose steroids.

794 www.pccmjournal.org October 2014 • Volume 15 • Number 8 Whether or not this is related to catabolism cannot be concluded from these data. We agree with Pritsch et al (2) that malnutrition is associated with several adverse outcome variables, including impaired immunity and muscle wasting. However, causality has never been demonstrated. Furthermore, whereas higher levels of protein intake may be required to attenuate the negative nitrogen/protein balance in critically ill patients, it remains unclear whether this is beneficial. Mechanisms may in part be reflected by measurement of whole-body protein turnover (3), which gives information of whole-body protein balance as well as protein (amino acid) oxidation (4). The results of such measurements may help to give recommendations on the composition of nutrition support in the future. Interestingly, the large multicenter randomized study Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) demonstrated in adult ICU patients that early supplementation of insufficient enteral nutrition with parenteral nutrition (early PN) increased the risk of new infections, delayed recovery of vital organ damage and weaning from artificial ventilation, and prolonged ICU and hospital stay, as compared with tolerating a substantial macronutrient deficit during the first week in ICU (late PN) (5). Analysis of the nitrogen balance in these patients indicated that whereas during the first week this balance was somewhat less negative with early PN, the effect reversed in the following days with a less negative balance in the late PN group and substantial loss of supplemental nitrogen in urine (6). Delayed recovery with early PN may be explained by suppression of autophagy, a crucial cellular quality control mechanism that is powerfully suppressed by nutrients, especially amino acids. This is supported by findings in muscle biopsies harvested during the EPaNIC study. Tolerating a substantial macronutrient deficit early during critical illness did not affect muscle wasting but allowed a more efficient activation of autophagy in the myofibers, reduced the prevalence of clinically relevant muscle weakness, and accelerated recovery from such weakness (7). We are currently performing the randomized controlled multicenter Early Parenteral Nutrition Completing Enteral Nutrition in Pediatric Critically Ill Patients study (ClinicalTrials.gov NCT01536275), a pediatric version of the EPaNIC study, which will provide answers to the question whether early PN is beneficial or not in critically ill children. The results are anxiously awaited. Supported, in part, by the TBM program of the Institute for Science and Technology–Flanders, Belgium (IWT 070695), the Swedish Medical Research Council (projects 04210 and 14244), and the Country Council of Stockholm (projects 502033 and 511126). Dr. Gielen received a Research Foundation-Flanders (FWO) Research Assistant Fellowship. Dr. Van den Berghe by the University of Leuven receives structural research financing via the Methusalem program, funded by the Flemish Government, and holds an ERC Advanced grant (AdvG-2012–321670) from the Ideas Program of the EU FP7. The remaining authors have disclosed that they do not have any potential conflicts of interest. Ilse Vanhorebeek, PhD, Marijke Gielen, MD, PhD, Pieter J. Wouters, MSc, Dieter Mesotten, MD, PhD, Clinical Department and Laboratory of Intensive Care Medicine, Division of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium; Jan Wernerman, MD, PhD, Olav Rooyackers, PhD, Department of Anaesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, Sweden, and Department of Clinical Science Intervention and Technology, CLINTEC, The Karolinska Institutet, Huddinge, Sweden; Greet Van den Berghe, MD, PhD, Clinical Department and Laboratory of Intensive Care Medicine, Division of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

LB026-MON: Type of Feeding and Risk of Bloodstream Infections in Critically Ill Patients

LB025-MON GLUTAMINE MAY ALTER THE WEAK LPS BUT NOT THE STRONG HEAT SHOCK INTRACELLULAR HSP72 INDUCTION IN CRITICALLY ILL PATIENTS E. Briassouli1, M. Tzanoudaki2, G. Daikos1, K. Vardas3, M. Kanariou2, C. Routsi3, S. Nanas3, G. Briassoulis4. 11st Department of Propaedeutic Internal Medicine, University of Athens, 2Department of Immunology Histocompatibility, Specialized Center & Referral Center for Primary Immunodeficiencies Paediatric Immunology, “Aghia Sophia” Children’s Hospital, 3First Critical Care Department, University of Athens, Athens, 4PICU, University of Crete/University Hospital, Heraklion, Crete, Greece