Extracorporeal membrane oxygenation during pregnancy and peripartal. An international retrospective multicenter study.

INTRODUCTION: Extracorporeal Membrane Oxygenation (ECMO) may be used in the setting of pregnancy or the peripartal period, however its utility has not been well-characterized. This study aims to give an overview on the prevalence of peripartel ECMO cases and further assess the indications and outcomes of ECMO in this setting across multiple centers and countries. METHODS: A retrospective, multicenter, international cohort study of pregnant and peripartum ECMO cases was performed. Data were collected from six ECMO centers across three continents over a 10-year period. RESULTS: A total of 60 pregnany/peripartal ECMO cases have been identified. Most frequent indications are acute respiratory distress syndrome (n = 30) and pulmonary embolism (n = 5). Veno-venous ECMO mode was applied more often (77%). ECMO treatment during pregnancy was performed in 17 cases. Maternal and fetal survival was high with 87% (n = 52), respectively 73% (n = 44). CONCLUSIONS: Various emergency scenarios during pregnancy and at time of delivery may require ECMO treatment. Peripartal mortality in a well-resourced setting is rare, however emergencies in the labor room occur and knowledge of available rescue therapy is essential to improve outcome. Obstetricians and obstetric anesthesiologists should be aware of the availability of ECMO resource at their hospital or region to ensure immediate contact when needed.

Cerebrovascular Autoregulation Monitoring in the Management of Adult Severe Traumatic Brain Injury: A Delphi Consensus of Clinicians.

BACKGROUND: Several methods have been proposed to measure cerebrovascular autoregulation (CA) in traumatic brain injury (TBI), but the lack of a gold standard and the absence of prospective clinical data on risks, impact on care and outcomes of implementation of CA-guided management lead to uncertainty. AIM: To formulate statements using a Delphi consensus approach employing a group of expert clinicians, that reflect current knowledge of CA, aspects that can be implemented in TBI management and CA research priorities. METHODS: A group of 25 international academic experts with clinical expertise in the management of adult severe TBI patients participated in this consensus process. Seventy-seven statements and multiple-choice questions were submitted to the group in two online surveys, followed by a face-to-face meeting and a third online survey. Participants received feedback on average scores and the rationale for resubmission or rephrasing of statements. Consensus on a statement was defined as agreement of more than 75% of participants. RESULTS: Consensus amongst participants was achieved on the importance of CA status in adult severe TBI pathophysiology, the dynamic non-binary nature of CA impairment, its association with outcome and the inadvisability of employing universal and absolute cerebral perfusion pressure targets. Consensus could not be reached on the accuracy, reliability and validation of any current CA assessment method. There was also no consensus on how to implement CA information in clinical management protocols, reflecting insufficient clinical evidence. CONCLUSION: The Delphi process resulted in 25 consensus statements addressing the pathophysiology of impaired CA, and its impact on cerebral perfusion pressure targets and outcome. A research agenda was proposed emphasizing the need for better validated CA assessment methods as well as the focused investigation of the application of CA-guided management in clinical care using prospective safety, feasibility and efficacy studies.

Elderly versus nonelderly patients with invasive aspergillosis in the ICU: a comparison and risk factor analysis for mortality from the AspICU cohort.

Data regarding the epidemiology and diagnosis of invasive aspergillosis in the critically ill population are limited, with data regarding elderly patients (≥75 years old) even scarcer. We aimed to further compare the epidemiology, characteristics and outcome of elderly versus nonelderly critically ill patients with invasive aspergillosis (IA) Prospective, international, multicenter observational study (AspICU) including adult intensive care unit (ICU) patients, with a culture and/or direct examination and/or histopathological sample positive for Aspergillus spp. at any site. We compared clinical characteristics and outcome of IA in ICU patients using two different diagnostic algorithms. Elderly and nonelderly ICU patients with IA differed in a number of characteristics, including comorbidities, clinical features of the disease, mycology testing, and radiological findings. No difference regarding mortality was found. According to the clinical algorithm, elderly patients were more likely to be diagnosed with putative IA. Elderly patients had less diagnostic radiological findings and when these findings were present they were detected late in the disease course. The comparison between elderly survivors and nonsurvivors demonstrated differences in clinical characteristics of the disease, affected sites and supportive therapy needed. All patients who were diagnosed with proven IA died. Increased vigilance combined with active search for mycological laboratory evidence and radiological confirmation are necessary for the timely diagnosis of IA in the elderly patient subset. Although elderly state per se is not a particular risk factor for mortality, a high SOFA score and the decision not to administer antifungal therapy may have an impact on survival of elderly patients.

Development of acute kidney injury during continuous infusion of vancomycin in septic patients.

PURPOSE: Few data are available on the occurrence of renal failure during continuous infusion of vancomycin in critically ill patients. METHODS: We reviewed the data of all patients admitted to the intensive care unit (ICU) between January 2008 and December 2009 in whom vancomycin was given as a continuous infusion for more than 48 h in the absence of renal replacement therapy. We collected data on the doses of vancomycin and blood concentrations during therapy. Acute kidney injury (AKI) was defined as a daily urine output <0.5 ml/kg/h and/or an increase in the serum creatinine of ≥0.3 mg/dl from baseline levels during vancomycin therapy or within 72 h after its discontinuation. Multivariable logistic regression analysis was performed to identify predictors of AKI. RESULTS: Of 207 patients who met the inclusion criteria, 50 (24 %) developed AKI. These patients were more severely ill, had lower creatinine clearance at admission, were more frequently exposed to other nephrotoxic agents, had a longer duration of therapy, and had higher concentrations of vancomycin during the first 3 days of treatment (C(mean)). The C(mean) was independently associated with early AKI (within 48 h from the onset of therapy) and the duration of vancomycin administration with late AKI. CONCLUSIONS: AKI occurred in almost 25 % of critically ill patients treated with a continuous infusion of vancomycin. Vancomycin concentrations and duration of therapy were the strongest variables associated with the development of early and late AKI during therapy, respectively.

Targeted Temperature Management After In-Hospital Cardiac Arrest: An Ancillary Analysis of Targeted Temperature Management for Cardiac Arrest With Nonshockable Rhythm Trial Data.

BACKGROUND: Targeted temperature management (TTM) currently is the only treatment with demonstrated efficacy in attenuating the harmful effects on the brain of ischemia-reperfusion injury after cardiac arrest. However, whether TTM is beneficial in the subset of patients with in-hospital cardiac arrest (IHCA) remains unclear. RESEARCH QUESTION: Is TTM at 33 °C associated with better neurological outcomes after IHCA in a nonshockable rhythm compared with targeted normothermia (TN; 37 °C)? STUDY DESIGN AND METHODS: We performed a post hoc analysis of data from the published Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm randomized controlled trial in 584 patients. We included the 159 patients with IHCA; 73 were randomized to 33 °C treatment and 86 were randomized to 37 °C treatment. The primary outcome was survival with a good neurologic outcome (cerebral performance category [CPC] score of 1 or 2) on day 90. Mixed multivariate adjusted logistic regression analysis was performed to determine whether survival with CPC score of 1 or 2 on day 90 was associated with type of temperature management after adjustment on baseline characteristics not balanced by randomization. RESULTS: Compared with TN for 48 h, hypothermia at 33 °C for 24 h was associated with a higher percentage of patients who were alive with good neurologic outcomes on day 90 (16.4% vs 5.8%; P = .03). Day 90 mortality was not significantly different between the two groups (68.5% vs 76.7%; P = .24). By mixed multivariate analysis adjusted by Cardiac Arrest Hospital Prognosis score and circulatory shock status, hypothermia was associated significantly with good day 90 neurologic outcomes (OR, 2.40 [95% CI, 1.17-13.03]; P = .03). INTERPRETATION: Hypothermia at 33 °C was associated with better day 90 neurologic outcomes after IHCA in a nonshockable rhythm compared with TN. However, the limited sample size resulted in wide CIs. Further studies of patients after cardiac arrest resulting from any cause, including IHCA, are needed.

Comparison between an uncalibrated pulse contour method and thermodilution technique for cardiac output estimation in septic patients.

BACKGROUND: The purpose of this study was to evaluate the reliability of a new uncalibrated pulse contour method, the MostCare, in determining cardiac output (CO) in septic patients. METHODS: Thirty patients with septic shock admitted to an intensive care unit, receiving a norepinephrine infusion and requiring haemodynamic monitoring with a pulmonary artery catheter, were prospectively enrolled. Thermodilution measurements of CO (ThD-CO) were considered as the 'gold standard'. MostCare was connected to the monitoring system of the radial arterial pressure waveform to obtain a continuous CO calculation (MostCare-CO). ThD-CO and MostCare-CO measurements were recorded at three different haemodynamic states: baseline (T1), after raising mean arterial pressure (MAP) to 90 mm Hg by increasing the norepinephrine infusion (T2), and after returning the MAP to baseline value by decreasing vasopressor therapy (T3). A Bland-Altman and linear regression analyses were performed. RESULTS: A total of 90 paired ThD-CO and MostCare-CO measures were obtained (range 4.1-13.9 litre min(-1) for ThD-CO and 4.5-13.5 litre min(-1) for MostCare-CO). A good correlation between ThD-CO and MostCare-CO was observed (R = 0.93). The mean bias between the two techniques was -0.26 litre min(-1) (sd 0.98 litre min(-1)) and the 95% limits of agreement were -2.22 to 1.70 litre min(-1). The percentage of error was 25%. Pearson's R was 0.94, 0.92, and 0.93 at T1, T2, and T3, respectively. CONCLUSIONS: MostCare-CO and ThD-CO showed a good agreement at each time of the study. The reliability of the MostCare system was not affected by the vascular tone changes produced by a norepinephrine infusion.

Correction to: Serum sodium and intracranial pressure changes after desmopressin therapy in severe traumatic brain injury patients: a multi-centre cohort study.

Following publication of the original article [1], we were notified that the collaborators' names part of the "The TBI Collaborative" group has not been indexed in Pubmed. Below the collaborators names full list.

Serum sodium and intracranial pressure changes after desmopressin therapy in severe traumatic brain injury patients: a multi-centre cohort study.

BACKGROUND: In traumatic brain injury (TBI) patients desmopressin administration may induce rapid decreases in serum sodium and increase intracranial pressure (ICP). AIM: In an international multi-centre study, we aimed to report changes in serum sodium and ICP after desmopressin administration in TBI patients. METHODS: We obtained data from 14 neurotrauma ICUs in Europe, Australia and UK for severe TBI patients (GCS ≤ 8) requiring ICP monitoring. We identified patients who received any desmopressin and recorded daily dose, 6-hourly serum sodium, and 6-hourly ICP. RESULTS: We studied 262 severe TBI patients. Of these, 39 patients (14.9%) received desmopressin. Median length of treatment with desmopressin was 1 [1-3] day and daily intravenous dose varied between centres from 0.125 to 10 mcg. The median hourly rate of decrease in serum sodium was low (- 0.1 [- 0.2 to 0.0] mmol/L/h) with a median period of decrease of 36 h. The proportion of 6-h periods in which the rate of natremia correction exceeded 0.5 mmol/L/h or 1 mmol/L/h was low, at 8% and 3%, respectively, and ICPs remained stable. After adjusting for IMPACT score and injury severity score, desmopressin administration was independently associated with increased 60-day mortality [HR of 1.83 (1.05-3.24) (p = 0.03)]. CONCLUSIONS: In severe TBI, desmopressin administration, potentially representing instances of diabetes insipidus is common and is independently associated with increased mortality. Desmopressin doses vary markedly among ICUs; however, the associated decrease in natremia rarely exceeds recommended rates and median ICP values remain unchanged. These findings support the notion that desmopressin therapy is safe.

Management strategies in venovenous extracorporeal membrane oxygenation: a retrospective comparison from five European centres.

OBJECTIVE: To investigate contemporary clinical practice in the management of venovenous (VV) extracorporeal membrane oxygenation (ECMO) in critically ill patients with bacterial pneumonia. METHODS: In this multicentre retrospective study, 48 patients with severe respiratory failure due to bacterial pneumonia receiving VV ECMO therapy in five experienced European ECMO centres were included. Ventilator and ECMO settings were analysed. RESULTS: Ventilator settings showed great variability between participating centres, particularly relating to positive end-expiratory pressure, peak inspiratory pressure and driving pressure. Different strategies in cannulation, ECMO setting and weaning procedures were also observed. CONCLUSION: There is great diversity in management modalities for ventilator and ECMO settings for patients with bacterial pneumonia. Our study emphasises the lack of clinical consensus in VV ECMO management.

Drivers and impact of antifungal therapy in critically ill patients with Aspergillus-positive respiratory tract cultures.

Invasive pulmonary aspergillosis (IPA) is an increasingly recognised problem in critically ill patients. Little is known about how intensivists react to an Aspergillus-positive respiratory sample or the efficacy of antifungal therapy (AFT). This study aimed to identify drivers of AFT prescription and diagnostic workup in patients with Aspergillus isolation in respiratory specimens as well as the impact of AFT in these patients. ICU patients with an Aspergillus-positive respiratory sample from the database of a previous observational, multicentre study were analysed. Cases were classified as proven/putative IPA or Aspergillus colonisation. Demographic, microbiological, diagnostic and therapeutic data were collected. Outcome was recorded 12 weeks after Aspergillus isolation. Patients with putative/proven IPA were more likely to receive AFT than colonised patients (78.7% vs. 25.5%; P <0.001). Patients with host factors for invasive fungal disease were more likely to receive AFT (72.5% vs. 37.4%) as were those with multiorgan failure (SOFA score >7) (68.4% vs. 36.9%) (both P <0.001). Once adjusted for disease severity, initiation of AFT did not alter the odds of survival (HR = 1.40, 95% CI 0.89-2.21). Likewise, treatment within 48 h following diagnosis did not change the clinical outcome (75.7% vs. 61.4%; P = 0.63). Treatment decisions appear to be based on diagnostic criteria and underlying disease severity at the time of Aspergillus isolation. IPA in this population has a dire prognosis and AFT is not associated with reduced mortality. This may be explained by delayed diagnosis and an often inevitable death due to advanced multiorgan failure.

[Spontaneous intrahepatic haemorrhage due to peliosis hepatis]. / Hémorragie intrahépatique spontanée révélant une péliose hépatique.

Liver vascular lesions may occur in women on oral contraceptives. We report here spontaneous liver haemorrhage caused by peliosis hepatis, occuring in a 47-year old patient. She used oral contraceptives for many years. A computerized tomography and a magnetic resonance of the abdomen revealed a subcapsular liver hematoma without hemoperitoneum. Treatment consisted of supportive care with favourable clinical outcome. This observation point out a severe complication of peliosis hepatis. The authors review the etiology, diagnosis, complications, treatment and potential role of estrogen/progesterone supplementation as an etiological factor, in peliosis hepatis.

How to monitor the brain in septic patients?

Brain injury is frequently observed after sepsis and may be primarily related to the direct effects of the septic insult on the brain (e.g., brain edema, ischemia, seizures) or to secondary/indirect injuries (e.g., hypotension, hypoxemia, hypocapnia, hyperglycemia). Management of brain injury in septic patients is first focused to exclude structural intracranial complications (e.g., ischemic/hemorrhagic stroke) and possible confounders (e.g., electrolyte alterations or metabolic disorders, such as dysglycemia). Sepsis-associated brain dysfunction is frequently a heterogeneous syndrome. Despite increasing understanding of main pathophysiologic determinants, therapy is essentially limited to protect the brain against further cerebral damage, by way of "simple" therapeutic manipulations of cerebral perfusion and oxygenation and by avoiding over-sedation. Non-invasive monitoring of cerebral perfusion and oxygenation with transcranial Doppler (TCD) and near-infrared spectroscopy (NIRS) is feasible in septic patients. Electroencephalography (EEG) allows detection of sepsis-related seizures and holds promise also as sedation monitoring. Brain CT-scan detects intra-cerebral structural lesions, while magnetic resonance imaging (MRI) provides important insights into primary mechanisms of sepsis-related direct brain injury, (e.g., cytotoxic vs. vasogenic edema) and the development of posterior reversible encephalopathy. Together with EEG and evoked potentials (EP), MRI is also important for coma prognostication. Emerging clinical evidence suggests monitoring of the brain in septic patients can be implemented in the ICU. The objective of this review was to summarize recent clinical data about the role of brain monitoring - including TCD, NIRS, EEG, EP, CT, and MRI - in patients with sepsis and to illustrate its potential utility for the diagnosis, management and prognostication.

Early-goal directed therapy for septic shock: is it the end?

Three randomized clinical trials have recently provided data on the lack of effectiveness of "early-goal directed therapy" (EGDT) (i.e. optimization of tissue oxygenation in the first 6 hours since sepsis diagnosis using different therapeutic interventions based on the assessment of the central venous oxygen saturation to titrate such interventions) in the initial management of patients with septic shock. In a first trial including 31 US hospitals (the ProCESS study, N.=1341), three different therapeutic strategies (EGDT vs. protocol-based therapy vs. usual care) were compared and no difference in the primary endpoint (60-day mortality) was found (EGDT 21%, protocol-based therapy 18% and usual care 19%). No significant difference in death by 90 days or in other secondary outcomes, including serious adverse events, was found, as well. A second trial (ARISE, N.=1600), mostly conducted in Australia and New Zealand, randomized patients to EGDT or usual care. Ninety-day mortality was similar between groups (19% vs. 19%, respectively; P=0.90) and no other differences in secondary endpoints were recorded between the two groups. A third study (ProMISe, N.=1260) included patients in 56 hospitals across England, randomly assigned to EGDT or usual care. By 90 days, mortality was similar between groups (29% vs. 29%, respectively; P=0.90). Moreover, EGDT significantly increased costs and was associated with a longer hospital length of stay. We discussed some issues related to the differences between these studies and the pivotal paper from Rivers et al. and how EGDT should be still considered in the treatment of sepsis.

Brain injury after cardiac surgery.

In patients undergoing cardiac surgery, postoperative brain injury significantly contributes to increase morbidity and mortality and has negative consequences on quality of life and costs. Moreover, over the past years, compelling medical and technological improvements have allowed an even older patients' population, with several comorbidities, to be treated with cardiac surgery; however, the risk of brain injury after such interventions is also increased in these patients. With the aim of improving post-operative neurological outcome, a variety of neuromonitoring methods and devices have been introduced in clinical practice. These techniques allow the assessment of a number of parameters, such as cerebral blood flow, brain embolic events, cerebral cortical activity, depth of anesthesia and brain oxygenation. Some of them have been used to optimize the hemodynamic management of such patients and to select specific therapeutic interventions. Also, various pharmacological and non-pharmacological approaches have been proposed to minimize the incidence of brain injury in this setting. In this review we describe the risk factors and mechanisms of cerebral injury after cardiac surgery and focus on monitoring techniques and clinical strategies that could help clinicians to minimize the incidence of brain injury.

Elevated ß-lactam concentrations associated with neurological deterioration in ICU septic patients.

BACKGROUND: Although ß-lactams are considered to have a safe therapeutic profile, neurotoxicity has been reported. The aim of this study was to assess the association between ß-lactam concentrations and neurological alterations in septic ICU patients. METHODS: Retrospective study on all ICU patients who were treated with meropenem (MEM), piperacillin-tazobactam (TZP) or ceftazidime/cefepime (CEF) and in whom at least one ß-lactam trough concentration (C min) was determined. Drug levels were measured using high-performance liquid chromatography; C min was normalized to the clinical breakpoint of Pseudomonas aeruginosa (as determined by EUCAST) for each drug (C min/MIC). Changes in neurological status were evaluated using changes in the neurological sequential organ failure assessment score (ΔnSOFA) using the formula: ΔnSOFA = nSOFA(day of TDM) - nSOFA(ICU admission). Worsening neurological status (NWS) was defined as a ΔnSOFA ≥ 1 for an nSOFA on admission of 0-2. RESULTS: We collected 262 C min in 199 patients (130 MEM, 85 TZP, 47 CEF). Median APACHE II score and GCS on admission were 17 and 15, respectively. Overall ICU mortality was 27 %. There were no differences in the occurrence of NWS between antibiotics (39% for MEM, 32% for TZP and 35% for CEF). The occurrence of NWS increased with increasing C min/MIC ranges (P = 0.008); this correlation was found for TZP (P = 0.05) and MEM (P = 0.01), but not for CEF. C min/MIC was an independent predictive factor for NWS (OR 1.12 [1.04-1.20]). CONCLUSION: We found a correlation between high ß-lactam trough concentrations and increased occurrence of neurological deterioration in septic ICU patients. Although our data cannot determine causality, monitoring of ß-lactam levels should be considered when deterioration of neurological status occurs during critical illness.

[Spondylo-costal dysostosis. Description of a case and review of the literature]. / Disostosi spondilo-costale. Descrizione di un caso e revisione della letteratura.

The Authors describe a case of spondylocostal dysostosis. The infant, born from consanguineous Caucasian parents, showed at birth marked shortening of the trunk and neck. Radiographic examination revealed severe congenital anomalies of the entire spine, associated with secondary deformities of the ribs. A review of literature's cases, with differential diagnosis and pathogenetic hypothesis, is also reported.

[Monosomy 9p. Clinical and cytogenetic aspects]. / La monosomia 9p. Aspetti clinici e citogenetici.

The Authors describe a new case of monosomy 9 p in a newborn, confirmed by bands technique. The parents had a normal karyotypes and this alteration was defined as deletion 9 p "de novo" arisen. The main morphological anomalies are described: these anomalies reproduce that reported by others and, for many aspects, remember Down syndrome. It is very important that the staff of the Neonatological Departments has a good knowledge of this syndrome since for the abnormal objective features, the diagnosis is possible already from the birth.

[HLA typing in a neonate with posttransfusional graft vs host disease (PT-GVHD)]. / Tipizzazione HLA in un neonato affetto da "graft versus host disease" post trasfusionale (PT-GVHD).

The authors report a case of post-transfusion-graft-versus-host disease (PT-GVHD) in a premature infant after parental blood donation. This disease seems to be due to the transfusion of immunocompetent T lymphocytes into an immunodeficient recipient or into an immunocompetent host who shares an HLA haplotype with HLA-homozygous blood donors (i.e. relatives or members of inbred populations) and who is therefore unable to reject the graft cells. The results of HLA typing of the patient and his family demonstrated that the infant was identical with his father for HLA class II antigens (DR, DQ) and, concerning HLA class I, he had in common the remaining paternal haplotype (A29, B44). Prevention of this disease, performed by gamma irradiation of blood components before transfusion, appears to be effective in most cases.

[Neonatal septic osteoarthritis]. / L'osteo artrite settica neonatale.

The Authors report their experience related to 15 cases of neonatal osteo-arthritis which have occurred in the last seven years in the neonatal intensive care unit. Besides the traditional clinical picture, it is stressed that neonatal osteo-arthritis has recently acquired new interest for an etiologic shift of the pathogens and for the availability of new antimicrobial agents. The rational antibiotic treatment and the role of the coordinated medical and orthopedic therapy have been essential for the benign clinical course and for the long-term prognosis. It is concluded that in order to reduce this serious disease it is necessary to avoid every potential risk factor, to operate in rigorous aseptic conditions and to improve the environmental conditions of the neonatal intensive care units.