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Importance: There are inconsistencies in concept, criteria, practice, and documentation of brain death/death by neurologic criteria (BD/DNC) both internationally and within countries., Objective: To formulate a consensus statement of recommendations on determination of BD/DNC based on review of the literature and expert opinion of a large multidisciplinary, international panel., Process: Relevant international professional societies were recruited to develop recommendations regarding determination of BD/DNC. Literature searches of the Cochrane, Embase, and MEDLINE databases included January 1, 1992, through April 2020 identified pertinent articles for review. Because of the lack of high-quality data from randomized clinical trials or large observational studies, recommendations were formulated based on consensus of contributors and medical societies that represented relevant disciplines, including critical care, neurology, and neurosurgery., Evidence Synthesis: Based on review of the literature and consensus from a large multidisciplinary, international panel, minimum clinical criteria needed to determine BD/DNC in various circumstances were developed., Recommendations: Prior to evaluating a patient for BD/DNC, the patient should have an established neurologic diagnosis that can lead to the complete and irreversible loss of all brain function, and conditions that may confound the clinical examination and diseases that may mimic BD/DNC should be excluded. Determination of BD/DNC can be done with a clinical examination that demonstrates coma, brainstem areflexia, and apnea. This is seen when (1) there is no evidence of arousal or awareness to maximal external stimulation, including noxious visual, auditory, and tactile stimulation; (2) pupils are fixed in a midsize or dilated position and are nonreactive to light; (3) corneal, oculocephalic, and oculovestibular reflexes are absent; (4) there is no facial movement to noxious stimulation; (5) the gag reflex is absent to bilateral posterior pharyngeal stimulation; (6) the cough reflex is absent to deep tracheal suctioning; (7) there is no brain-mediated motor response to noxious stimulation of the limbs; and (8) spontaneous respirations are not observed when apnea test targets reach pH <7.30 and Paco2 ≥60 mm Hg. If the clinical examination cannot be completed, ancillary testing may be considered with blood flow studies or electrophysiologic testing. Special consideration is needed for children, for persons receiving extracorporeal membrane oxygenation, and for those receiving therapeutic hypothermia, as well as for factors such as religious, societal, and cultural perspectives; legal requirements; and resource availability., Conclusions and Relevance: This report provides recommendations for the minimum clinical standards for determination of brain death/death by neurologic criteria in adults and children with clear guidance for various clinical circumstances. The recommendations have widespread international society endorsement and can serve to guide professional societies and countries in the revision or development of protocols and procedures for determination of brain death/death by neurologic criteria, leading to greater consistency within and between countries.

The measurement of optic nerve sheath diameter (ONSD) has been reported as a non-invasive marker for intracranial pressure (ICP). Nevertheless, it is uncertain whether possible ONSD differences occur with age and sex in healthy and brain-injured populations. The aim of this study was to investigate the effects of sex and age on ONSD in healthy volunteers and patients with traumatic brain injury. We prospectively included 122 healthy adult volunteers (Galliera Hospital, Genova, Italy), and compared age/sex dependence of ONSD to 95 adult patients (Addenbrooke's Hospital, Cambridge, UK) with severe traumatic brain injury (TBI) requiring intubation and invasive ICP monitoring. The two groups were stratified for sex and age. Age was divided into 3 subgroups: (1) young adults: 18-44 years; (2) middle-aged adults: 45-64 years; (3) old adults: >65 years. In healthy volunteers, ONSD was significantly different between males and females [median (interquartile range): 4.2 (3.9-4.6) mm vs. 4.1 (3.6-4.2) mm ( p = 0.01), respectively] and was correlated with age (R = 0.50, p < 0.0001). ONSD was significantly increased in group 3 compared to groups 2 and 1, indicating that ONSD values are higher in elderly subjects. In TBI patients, no differences in ONSD were found for sex and the correlation between ONSD and age was non-significant (R = 0.13, p = 0.20). ONSD increases with age and is significantly larger for males in healthy volunteers but not in TBI patients. Different ONSD cut-off values need not be age- or sex-adjusted for the assessment of increased ICP in TBI patients., (Copyright © 2020 Cardim, Czosnyka, Chandrapatham, Badenes, Bertuccio, Noto, Donnelly, Pelosi, Ball, Hutchinson and Robba.)

Background: A major contributor to unfavorable outcome after traumatic brain injury (TBI) is secondary brain injury. Low brain tissue oxygen tension (PbtO2) has shown to be an independent predictor of unfavorable outcome. Although PbtO2 provides clinicians with an understanding of the ischemic and non-ischemic derangements of brain physiology, its value does not take into consideration systemic oxygenation that can influence patients' outcomes. This study analyses brain and systemic oxygenation and a number of related indices in TBI patients: PbtO2, partial arterial oxygenation pressure (PaO2), PbtO2/PaO2, ratio of PbtO2 to fraction of inspired oxygen (FiO2), and PaO2/FiO2. The primary aim of this study was to identify independent risk factors for cerebral hypoxia. Secondary goal was to determine whether any of these indices are predictors of mortality outcome in TBI patients. Materials and Methods: A single-centre retrospective cohort study of 70 TBI patients admitted to the Neurocritical Care Unit (NCCU) at Cambridge University Hospital in 2014-2018 and undergoing advanced neuromonitoring including invasive PbtO2 was conducted. Three hundred and three simultaneous measurements of PbtO2, PaO2, PbtO2/PaO2, PbtO2/FiO2, PaO2/FiO2 were collected and mortality at discharge from NCCU was considered as outcome. Generalized estimating equations were used to analyse the longitudinal data. Results: Our results showed PbtO2 of 28 mmHg as threshold to define cerebral hypoxia. PaO2/FiO2 found to be a strong and independent risk factor for cerebral hypoxia when adjusting for confounding factor of intracranial pressure (ICP) with adjusted odds ratio of 1.78, 95% confidence interval of (1.10-2.87) and p -value = 0.019. With respect to TBI outcome, compromised values of PbtO2, PbtO2/PaO2, PbtO2/FiO2, and PaO2/FiO2 were all independent predictors of mortality while considered individually and adjusting for confounding factors of ICP, age, gender, and cerebral perfusion pressure (CPP). However, when considering all the compromised values together, only PaO2/FiO2 became an independent predictor of mortality with adjusted odds ratio of 3.47 (1.20-10.04) and p -value = 0.022. Conclusions: Brain and Lung interaction in TBI patients is a complex interrelationship. PaO2/FiO2 seems to be a major determinant of cerebral hypoxia and mortality. These results confirm the importance of employing ventilator strategies to prevent cerebral hypoxia and improve the outcome in TBI patients., (Copyright © 2020 Robba, Asgari, Gupta, Badenes, Sekhon, Bequiri, Hutchinson, Pelosi and Gupta.)

Introduction: Hyperosmotic therapy with mannitol is frequently used for treatment cerebral edema, and 320 mOsm/kg H 2 O has been recommended as a high limit for therapeutic plasma osmolality. However, plasma hyperosmolality may impair cardiac function, increasing the risk of cardiac events. The aim of this study was to analyze the relation between changes in plasma osmolality and electrocardiographic variables and cardiac arrhythmia in patients treated for isolated traumatic brain injury (iTBI)., Methods: Adult iTBI patients requiring mannitol infusion following cerebral edema, and with a Glasgow Coma Score below 8, were included. Plasma osmolality was measured with Osmometr 800 CLG. Spatial QRS-T angle (spQRS-T), corrected QT interval (QTc) and STJ segment were calculated from digital resting 12-lead ECGs and analyzed in relation to four levels of plasma osmolality: A) <280 mOsm/kg H 2 O; B) 280-295 mOsm/kg H 2 O; C) 295-310 mOsm/kg H 2 O; and D) >310 mOsm/kg H 2 O. All parameters were measured during five consecutive days of treatment., Results: 94 patients aged 18-64 were studied. Increased plasma osmolality correlated with prolonged QTc (p < 0.001), intensified disorders in STJ and increased the risk for cardiac arrhythmia. Moreover, plasma osmolality >313 mOms/kg H 2 O significantly increased the risk of QTc prolongation >500 ms., Conclusion: In patients treated for iTBI, excessively increased plasma osmolality contributes to electrocardiographic disorders including prolonged QTc, while also correlating with increased risk for cardiac arrhythmias., Competing Interests: The authors state no conflict of interest

Background: In patients with subarachnoid hemorrhage (SAH), abnormalities in glucose and lactate metabolism have been described using cerebral microdialysis. Glucose and lactate concentrations in cerebrospinal fluid (CSF) are more easily accessible, but scarce data are available in this setting. The aim of this study is to assess the relationship of CSF glucose and lactate with blood concentrations and with unfavorable neurological outcome after SAH., Methods: A retrospective cohort study was conducted in 5 European University intensive care units. Patients aged 18 years and above who were admitted after a nontraumatic SAH over a 4-year period (2011 to 2014) were included if they had an external ventricular drain placed, daily analysis of CSF including glucose (±lactate) concentrations for 1 to 4 consecutive days, and concomitant analysis of glucose and lactate concentrations in the arterial blood., Results: A total of 144 patients were included in the final analysis (median age: 58 [49 to 66] y; male sex: 77/144). Median time from admission to external ventricular drain placement was 1 (0 to 3) day; median Glasgow Coma Scale on admission was 10 (7 to 13), and CT-scan Fisher scale was 4. A total of 81 (56%) patients had unfavorable neurological outcome at 3 months (Glasgow Outcome Scale ≤3). There was a weak correlation between blood and CSF glucose (r=0.07, P=0.007), and between blood and CSF lactate levels (r=0.58, P<0.001) on day 1, which were not influenced by insulin therapy. The presence of shock and low CSF glucose/lactate ratio were the only independent predictors of unfavorable outcome., Conclusions: CSF glucose and lactate levels poorly correlated with blood concentrations. Low CSF glucose/lactate ratio was associated with poor neurological outcome.

Background: Studies in which brain metabolism has been monitored using microdialysis have indicated decreases in cerebral glucose concentration and increases in lactate concentration in patients with traumatic brain injury (TBI). However, few data are available on glucose and lactate concentrations in the cerebrospinal fluid (CSF) of TBI patients. This study investigates the relationship between CSF glucose and lactate concentrations and outcomes after TBI., Methods: Consecutive adult (>18 y) TBI patients were admitted to our 35-bed medicosurgical between 2011 and 2014 and were included in the study if they met the following inclusion criteria: presence of an external ventricular drain (EVD) for intracranial pressure monitoring, daily analysis of CSF glucose and lactate concentrations for 4 consecutive days, and concomitant measurements of blood glucose/lactate concentrations. Neurological outcome was assessed at 3 months using the extended Glasgow Outcome Scale (GOS), and unfavorable outcome defined as a GOS 1 to 4., Results: Of 151 TBI patients who had an EVD, 56 met the inclusion criteria. Most EVDs were placed on the day of intensive care unit admission, and maintained for 10 (interquartile range: 6 to 14) days. On day 1, there was a weak but significant correlation between blood and CSF glucose concentrations (R=0.07, P=0.04), and a greater correlation between blood and CSF lactate (R=0.32, P<0.001). In multivariable analysis, day 1 CSF glucose/lactate ratio was independently associated with mortality (odds ratio: 0.22, 95% confidence interval: 0.08-0.61; P=0.003), and day 1 CSF lactate concentration with unfavorable outcome (odds ratio: 4.86; 95% confidence interval: 1.86-12.67; P=0.001)., Conclusions: Low CSF glucose/lactate ratio is observed in nonsurvivors after severe TBI and may have prognostic value.

The optimal osmotic agent to treat intracranial hypertension in patients with severe traumatic brain injury (TBI) remains uncertain. We aimed to test whether the choice of mannitol or hypertonic saline (HTS) as early (first 96 h) osmotherapy in these patients might be associated with a difference in mortality. We retrospectively analyzed data from 2015 from 14 tertiary intensive care units (ICUs) in Australia, UK, and Europe treating severe TBI patients with intracranial pressure (ICP) monitoring and compared mortality in those who received mannitol only versus HTS only. We performed multi-variable analysis adjusting for site and illness severity (Injury Severity Score, extended IMPACT score, and mean ICP over the first 96 h) using Cox proportional hazards regression. We collected data on 262 patients and compared patients who received early osmotherapy with mannitol alone ( n  = 46) with those who received HTS alone ( n  = 46). Mannitol patients were older (median age, 49.2 (19.2) vs. 40.5 (16.8) years; p  = 0.02), with higher Injury Severity Scores (42 (15.9) vs. 32.1 [11.3]; p  = 0.001), and IMPACT-TBI predicted 6-month mortality (34.5% [23-46] vs. 25% [13-38]; p  = 0.02), but had similar APACHE-II scores, and mean and maximum ICPs over the first 96 h. The unadjusted hazard ratio for in-hospital mortality in patients receiving only mannitol was 3.35 (95% confidence interval [CI], 1.60-7.03; p  = 0.001). After adjustment for key mortality predictors, the hazard ratio for in-hospital mortality in patients receiving only mannitol was 2.64 (95% CI, 0.96-7.30; p  = 0.06). The choice of early osmotherapy in severe TBI patients may affect survival, or simply reflect clinician beliefs about their different roles, and warrants controlled investigation.

Continuous monitoring of cerebral oxygenation and its application to the management of the severe neurological patient is a challenge for the management of patients with acute critical brain damage. Although several techniques have been described for monitoring brain, brain tissue oxygen monitoring provides relevant information about oxygen levels of brain tissue. However, the development of this technique has been associated with the need to answer not only some technical aspects of it as well as the meaning of the changes of the cerebral oxygenation in the neurocritical patient. The consensus document responds to various questions related to the monitoring of cerebral oxygenation by means of a cerebral oxygen tissue pressure sensor. For this purpose, a list of questions was prepared and a reviewed of the medical literature was made. The quality of the evidence and the degree of recommendation was evaluated using the GRADE methodology., (Copyright © 2019 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.)

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.

Lack of homogeneity in the product (LHP) is a problem when customers require homogeneous units of a single product. In such cases, the optimal allocation of inventory to orders becomes much more complex. Furthermore, in an MTS environment, an optimal initial allocation may become less than ideal over time, due to different circumstances. This problem occurs in the ceramics sector, where the final product varies in tone and calibre. This paper proposes a methodology for the reallocation of inventory to orders in LHP situation (MERIO-LHP) and a model-based decision-support system (DSS) to support the methodology, which enables an optimal reallocation of inventory to order lines to be carried out in real businesses environments in which LHP is inherent. The proposed methodology and model-based DSS were validated by applying it to a real case at a ceramics company. The analysis of the results indicates that considerable improvements can be obtained with regard to the quantity of orders fulfilled and sales turnover., Competing Interests: The authors have declared that no competing interests exist.

Background: High red cell distribution width (RDW) values have been associated with increased hospital mortality in critically ill patients, but few data are available for subarachnoid hemorrhage (SAH)., Methods: We analyzed an institutional database of adult (>18 y) patients admitted to the Department of Intensive Care after nontraumatic SAH between January 2011 and May 2016. RDW (normal value, 10.9% to 13.4%) was obtained daily from admission for a maximum of 7 days, from routine blood analysis. We recorded the occurrence of delayed cerebral ischemia (DCI), and neurological outcome (assessed using the Glasgow Outcome Scale [GOS]) at 3 months., Results: A total of 270 patients were included (median age 54 y-121/270 male [45%]), of whom 96 (36%) developed DCI and 109 (40%) had an unfavorable neurological outcome (GOS, 1 to 3). The median RDW on admission was 13.8 [13.3 to 14.5]% and the highest value during the intensive care unit (ICU) stay 14.2 [13.6 to 14.8]%. The RDW was high (>13.4%) in 177 patients (66%) on admission and in 217 (80%) at any time during the ICU stay. Patients with a high RDW on admission were more likely to have an unfavorable neurological outcome. In multivariable regression analysis, older age, a high WFNS grade on admission, presence of DCI or intracranial hypertension, previous neurological disease, vasopressor therapy and a high RDW (OR, 1.1618 [95% CI, 1.213-2.158]; P=0.001) during the ICU stay were independent predictors of unfavorable neurological outcome., Conclusions: High RDW values were more likely to result in an unfavorable outcome after SAH. This information could help in the stratification of SAH patients already on ICU admission.

Traumatic brain injury (TBI) is an important cause of morbidity and mortality worldwide. TBI patients frequently suffer from lung complications and acute respiratory distress syndrome (ARDS), which is associated with poor clinical outcomes. Moreover, the association between TBI and ARDS in trauma patients is well recognized. Mechanical ventilation of patients with a concomitance of acute brain injury and lung injury can present significant challenges. Frequently, guidelines recommending management strategies for patients with traumatic brain injuries come into conflict with what is now considered best ventilator practice. In this review, we will explore the strategies of the best practice in the ventilatory management of patients with ARDS and TBI, concentrating on those areas in which a conflict exists. We will discuss the use of ventilator strategies such as protective ventilation, high positive end expiratory pressure (PEEP), prone position, recruitment maneuvers (RMs), as well as techniques which at present are used for 'rescue' in ARDS (including extracorporeal membrane oxygenation) in patients with TBI. Furthermore, general principles of fluid, haemodynamic and hemoglobin management will be discussed. Currently, there are inadequate data addressing the safety or efficacy of ventilator strategies used in ARDS in adult patients with TBI. At present, choice of ventilator rescue strategies is best decided on a case-by-case basis in conjunction with local expertise., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Purpose of Review: The current article revises the recent evidence on ICU admission criteria and postoperative neuromonitoring for patients undergoing elective craniotomy., Recent Findings: Only a small proportion of elective postoperative neurosurgical patients require specific medical interventions and invasive monitoring. Among these, patients undergoing elective craniotomy are frequently admitted to neuro-ICU, specialist postanaesthesia care units or intermediate-level care unit in the postoperative period.Craniotomy patients have a high risk of neurological complications in the immediate postoperative period and might require advanced neuromonitoring, especially if sedation is continued in the ICU.Furthermore, the concept of enhanced recovery after surgery with the goal of improving functional capacity after surgery and decreasing morbidity has expanded to encompass neurosurgery.Postoperative clinical examination and neurological scores, bispectral index and simplified electroencephalography, and morning discharge huddles are the most used strategies in this context., Summary: After elective craniotomy, ICU admission should be warranted to patients who show new neurological deficits, especially when these include reduced consciousness or deficits of the lower cranial nerves, or have surgical indication for delayed extubation. Currently, evidence does not allow defining standardized protocol to guide ICU admission and postoperative neuromonitoring.

Background: The optimal hemoglobin (Hb) threshold at which to initiate red blood cell (RBC) transfusion in patients with acute brain injury is unknown. The aim of this survey was to investigate RBC transfusion practices used with these patients., Methods: We conducted a web-based survey within various societies of critical care medicine for intensive care unit (ICU) physicians who currently manage patients with primary acute brain injury., Results: A total of 868 responses were obtained from around the world, half of which (n = 485) were from European centers; 204 (24%) respondents had a specific certificate in neurocritical care, and most were specialists in anesthesiology or intensive care and had less than 15 years of practice experience. Four hundred sixty-six respondents (54%) said they used an Hb threshold of 7-8 g/dl to initiate RBC transfusion after acute brain injury, although half of these respondents used a different threshold (closer to 9 g/dl) in patients with traumatic brain injury, subarachnoid hemorrhage, or ischemic stroke. Systemic and cerebral factors were reported as influencing the need for higher Hb thresholds. Most respondents agreed that a randomized clinical trial was needed to compare two different Hb thresholds for RBC transfusion, particularly in patients with traumatic brain injury, subarachnoid hemorrhage, and ischemic stroke., Conclusions: The Hb threshold used for RBC transfusion after acute brain injury was less than 8 g/dl in half of the ICU clinicians who responded to our survey. However, more than 50% of these physicians used higher Hb thresholds in certain conditions.

We propose an integrated and adaptable approach to improve patient care and clinical outcomes through analgesia and light sedation, initiated early during an episode of critical illness and as a priority of care. This strategy, which may be regarded as an evolution of the Pain, Agitation and Delirium guidelines, is conveyed in the mnemonic eCASH-early Comfort using Analgesia, minimal Sedatives and maximal Humane care. eCASH aims to establish optimal patient comfort with minimal sedation as the default presumption for intensive care unit (ICU) patients in the absence of recognised medical requirements for deeper sedation. Effective pain relief is the first priority for implementation of eCASH: we advocate flexible multimodal analgesia designed to minimise use of opioids. Sedation is secondary to pain relief and where possible should be based on agents that can be titrated to a prespecified target level that is subject to regular review and adjustment; routine use of benzodiazepines should be minimised. From the outset, the objective of sedation strategy is to eliminate the use of sedatives at the earliest medically justifiable opportunity. Effective analgesia and minimal sedation contribute to the larger aims of eCASH by facilitating promotion of sleep, early mobilization strategies and improved communication of patients with staff and relatives, all of which may be expected to assist rehabilitation and avoid isolation, confusion and possible long-term psychological complications of an ICU stay. eCASH represents a new paradigm for patient-centred care in the ICU. Some organizational challenges to the implementation of eCASH are identified.

Purpose of Review: This article reviews the recent evidence on perioperative neuroprotection in patients undergoing brain surgery and in patients with acute stroke., Recent Findings: With varying degrees of success, numerous pharmacological and nonpharmacological therapies have been employed to provide neuroprotection for patients during the perioperative period and after acute ischemic stroke (IAS). Recent studies have failed to demonstrate neuroprotective effects of intraoperative remifentanil or propofol use, although hypertonic saline may provide better brain relaxation than mannitol during elective intracranial surgery for tumor. Magnesium sulfate offers no improvement in neurological outcome at 90 days after stroke. Medical management alone may be superior to medical management with interventional therapy for the prevention of death or stroke in unruptured arteriovenous malformations. In patients with IAS with a proximal vessel occlusion, small infarct core, and moderate-to-good collateral circulation, rapid endovascular treatment resulted in improved functional outcomes and reduced mortality. For endovascular clot evacuation after IAS, conscious sedation may be safer than general anaesthesia., Summary: Recent evidence provides insufficient evidence of neuroprotective strategies to guide clinical management, and more randomized clinical trials are needed to optimize patient care.

Introduction: The aim of this multicenter, prospective, randomized, crossover trial is to compare, in critical care patients receiving insulin infusion therapy (IIT), the pharmacodynamic of Humulin insulin (Hlin), currently used as "standard of care," and Humalog insulin (Hlog), a shorter acting insulin formulation. This was measured as extent and duration of the carryover effect of insulin treatment, with the latter calculated as ratio between blood glucose concentration (BGC) reduction during and after IIT., Materials and Methods: Twenty-eight patients treated in an intensive care unit and receiving full nutritional support were randomly assigned to Hlin or Hlog as first treatment. Insulin was infused at a constant rate in patients presenting with BGC greater than or equal to 180 mg/dL (0.04 U/kg per hour) and was discontinued when BGC was less than or equal to 140 mg/dL (therapeutic BGC drop). Further reductions in BGC after discontinuation of insulin infusion were recorded (postinfusional BGC drop). During the study period, whole blood BGC was measured every 30 minutes. A minimal 6-hour washout interval was maintained between treatments with the 2 types of insulin. The primary end point was the extent (calculated as ratio between the therapeutic BGC drop and the postinfusional BGC drop) and duration of the carryover effect., Results: Treatment with Hlog, as compared with Hlin, was associated with a less profound carryover effect as well as a briefer duration of carryover (median, 0.40 vs 0.62; P < .001; median, 1 vs 1.5 hours; P < .001)., Conclusions: The use of constant Hlog infusion for IIT, when compared with Hlin at the same dose, is associated with a less profound carryover effect on BGC after discontinuation of IIT, a briefer duration of carryover, a faster BGC drop during infusion, and a quicker BGC rise after discontinuation. These characteristics suggest that Hlog IIT may be preferable for use in critically ill patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Postoperative pulmonary dysfunction (PPD) is a frequent and significant complication after cardiac surgery. It contributes to morbidity and mortality and increases hospitalization stay and its associated costs. Its pathogenesis is not clear but it seems to be related to the development of a systemic inflammatory response with a subsequent pulmonary inflammation. Many factors have been described to contribute to this inflammatory response, including surgical procedure with sternotomy incision, effects of general anesthesia, topical cooling, and extracorporeal circulation (ECC) and mechanical ventilation (VM). Protective ventilation strategies can reduce the incidence of atelectasis (which still remains one of the principal causes of PDD) and pulmonary infections in surgical patients. In this way, the open lung approach (OLA), a protective ventilation strategy, has demonstrated attenuating the inflammatory response and improving gas exchange parameters and postoperative pulmonary functions with a better residual functional capacity (FRC) when compared with a conventional ventilatory strategy. Additionally, maintaining low frequency ventilation during ECC was shown to decrease the incidence of PDD after cardiac surgery, preserving lung function.

BLOOD GLUCOSE CONTROL IN INTENSIVE CARE UNIT (ICU) PATIENTS, ADDRESSED TO ACTIVELY MAINTAIN BLOOD GLUCOSE CONCENTRATION WITHIN DEFINED THRESHOLDS, IS BASED ON TWO MAJOR THERAPEUTIC INTERVENTIONS: to supply an adequate calories load and, when necessary, to continuously infuse insulin titrated to patients needs: intensive insulin therapy (IIT). Short acting insulin analogues (SAIA) have been synthesized to improve the chronic treatment of patients with diabetes but, because of the pharmacokinetic characteristics that include shorter on-set and off-set, they can be effectively used also in ICU patients and have the potential to be associated with a more limited risk of inducing episodes of iatrogenic hypoglycemia. Medical therapies carry an intrinsic risk for collateral effects; this can be more harmful in patients with unstable clinical conditions like ICU patients. To minimize these risks, the use of short acting drugs in ICU patients have gained a progressively larger room in ICU and now pharmaceutical companies and researchers design drugs dedicated to this subset of medical practice. In this article we report the rationale of using short acting drugs in ICU patients (i.e., sedation and treatment of arterial hypertension) and we also describe SAIA and their therapeutic use in ICU with the potential to minimize iatrogenic hypoglycemia related to IIT. The pharmacodynamic and pharmachokinetic characteristics of SAIA will be also discussed.

Background: Anidulafungin is indicated as a first-line treatment for invasive candidiasis in critically ill patients. In the intensive care unit, sepsis is the main cause of acute renal failure, and treatment with continuous renal replacement therapy (CRRT) has increased in recent years. Antimicrobial pharmacokinetics is affected by CRRT, but few studies have addressed the optimal dosage for anidulafungin during CRRT., Patients and Methods: We included 12 critically ill patients who received continuous venovenous haemodiafiltration to treat acute renal failure. Anidulafungin was infused on 3 consecutive days, starting with a loading dose (200 mg) on Day 1, and doses of 100 mg on Days 2 and 3. Blood and ultradiafiltrate samples were collected on Day 3 (during steady-state) before, and at regular intervals after, the infusion had started. Anidulafungin concentrations were determined with HPLC., Results: On Day 3, peak plasma concentrations with the 100 mg dose were 6.2 ± 1.7 mg/L and 7.1 ± 1.9 mg/L in the arterial and venous samples, respectively. The mean, pre-filter trough concentration was 3.0 ± 0.6 mg/L. The mean AUC0-24 values for plasma anidulafungin were 93.9 ± 19.4 and 104.1 ± 20.3mg·h/L in the arterial and venous samples, respectively. There was no adsorption to synthetic surfaces, and the anidulafungin concentration in the ultradiafiltrate was below the limit of detection., Conclusion: The influence of CRRT on anidulafungin elimination appeared to be negligible. Therefore, we recommend no adjustments to the anidulafungin dose for patients receiving CRRT., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Sedation in neurocritical patients remains a challenge as there is no drug that meets all the requirements. Since the appearance of the AnaConDa(®) device, and according to the latest recommendations, sevoflurane has become an alternative for patients with brain injury. The use of AnaConDa(®) produces an increase in the anatomical dead space that leads to a decrease in alveolar ventilation. If the decrease in the alveolar ventilation is not offset by an increase in minute volume, there will be an increase in PaCO2. We report the case of a patient with severe traumatic brain injury who suffered an increase in intracranial pressure as a result of increased PaCO2 after starting sedation with the AnaConDa(®) device., (Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.)

Seriously ill patients frequently present intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) as complications, and the associated mortality is very high. This review offers an update on the most controversial aspects of these entities: factors favoring their appearance, the most common causes, prognosis, and methods of measuring intra-abdominal pressure (IAP), physiopathological consequences in relation to the different organs and systems, and the currently accepted treatment measures (medical and/or surgical). Simultaneously to the strictly physical mechanisms of injury, such as direct compression of intra-abdominal organs and vessels, the transmission of IAP to other compartments, and the drop in cardiac output, a series of immune-inflammatory mediators generated in the intestine itself may also intervene. Hypoperfusion, sustained ischemia and the ischemia-reperfusion phenomenon, would act upon the microbiota, intestinal epithelium and intestinal immune system, triggering a systemic inflammatory response and multiorgan dysfunction that appears in the final stages of ACS., (Copyright © 2011 Elsevier España, S.L. and SEMICYUC. All rights reserved.)

Background: Critically ill patients with invasive candidiasis (IC) often suffer renal failure, which sometimes requires continuous renal replacement techniques (CRRT). Echinocandins are the first line treatment for IC in critically ill patients with mild or severe illness. Their elimination during CRRT should be negligible due to their pharmacokinetic and pharmacodynamic (PK/PD) profile, and dose adjustment are not needed, as suggested by the few reported clinical studies., Clinical Case: This is the case of a 66 year old male who underwent surgery due to peritonitis secondary to intestinal suture dehiscence. The patient was admitted to ICU with septic shock symptoms and multiple organ dysfunction syndrome (MODS), and CRRT was started. Anidulafungin was prescribed at the usual dosage due to the IC risk factors present, and the observation of yeasts in the peritoneal fluid. Anidulafungin was selected due to the hepatic failure suffered by the patient. An isolate of Candida albicans susceptible to fluconazole was cultured from peritoneal fluid and rectal exudates. However, anidulafungin was maintained due to the MODS and observing the clearance of fluconazole during CRRT. The patient's condition improved favourably, being moved to the surgical ward 20 days after the surgery., Conclusions: Echinocandins, due to their PK/PD profile, could be safely given at usual doses to critically ill patients undergoing CRRT. However, new studies are required to strengthen this recommendation. Its extrahepatic metabolism makes anidulafungin a more attractive option among echinocandins and other antifungals when used in patients with different degrees of hepatic failure., (Copyright © 2012 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.)

Background: The Anesthetic Conserving Device--AnaConDa® (ACD)--has been compared with a conventional vaporizer. However, the accuracy of the administered concentration of volatile anesthetics was not examined. In the present study we measured the accuracy of the ACD when used as a portable vaporizer., Methods: This prospective study included 30 ASA I-III patients scheduled for elective surgery under general anesthesia. The patients were randomly organized into 3 groups of 10 patients per group. In each group, the sevoflurane infusion rate was adjusted to deliver 1.0 vol%, 1.5 vol%, and 2.0 vol% alveolar concentration. Hemodynamic data, bispectral index, and end-tidal sevoflurane concentrations were recorded every 2 minutes., Results: We analyzed 801 data points from 30 patients. The mean difference between the end-tidal sevoflurane concentration and the target concentration was -11.0 ± 9.3% of the target when the target was 1.0 vol%, -5.4 ± 6.4% when the target was 1.5 vol%, and -4.0 ± 7.4% when the target was 2.0 vol%. No significant differences were found in the error at the different target concentrations., Conclusions: We found that the ACD may be a valid alternative to the conventional vaporizer. The ACD is very simple to use, delivery rate needs to be adjusted only once per hour, and the anesthetic savings are independent of the circuit characteristics and fresh gas flow rate.

Background: The Anesthetic-Conserving Device (AnaConDa) can be used to administer inhaled anesthetics using an intensive care unit (ICU) ventilator. We evaluated the predictive performance of a simple manually adjusted pump infusion scheme, for infusion of liquid sevoflurane to the AnaConDa., Methods: We studied 50 ICU patients who received sevoflurane via the AnaConDa. They were randomly divided into three groups. A 6-h infusion of liquid anesthetic was adjusted according to the infusion scheme to a target end-tidal sevoflurane concentration of 1% (Group 1%, n = 15) and 1.5% (Group 1.5%, n = 15). The initial rate was adjusted to reach the target concentration in 10 min and then the infusion was reduced to the first hour maintenance rate and readjusted once each hour afterwards. The actual concentrations were measured in the breathing circuit and compared with the target values. In the third group (n = 20) we used the model to increase and decrease the target concentration (+/-0.3%) for 3 h and evaluated the actual change in concentration achieved. The ability of the infusion scheme to provide the target concentration was quantified by calculating the performance error (PE). Infusion scheme performance was evaluated in terms of accuracy (median absolute PE, MDAPE) and bias (median PE, MDPE)., Results: Performance parameters (mean +/- SD, %) were for 1%, 1.5%, increase of concentration by 0.3% and decrease of concentration by 0.3% groups, respectively: MDAPE 5.3 +/- 5.5, 2.6 +/- 4.0, 5.0 +/- 5.6, 5.5 +/- 5.4; MDPE -5.3 +/- 5.5, -2.3 +/- 4.1, -0.1 +/- 7.1, 0.2 +/- 5.4. No significant differences were found between means of all performance parameters when the 1% and 1.5% groups were compared., Conclusions: There is an excellent 6-h predictive performance of a simplified pharmacokinetic model for manually adjusted infusion of liquid sevoflurane when using the AnaConDa to deliver sevoflurane to ICU patients.

Background: Spinal cord stimulation (SCS) is used to treat chronic pain and requires an awake patient for optimized lead positioning to locate paresthesias. Epidural anesthesia may be a suitable anesthetic but has not been evaluated., Methods: We performed an open-label, prospective, observational, single-center study to evaluate the safety and efficacy of laminectomy lead placement under epidural anesthesia for the treatment of neuropathic chronic pain., Results: The results in our study demonstrate that epidural anesthesia is a suitable technique for SCS lead implant., Conclusions: This is the first study using epidural anesthesia for SCS lead implants by laminectomy. The technique seems to be safe and effective.

Headache is one of the most frequent complications of the subarachnoid puncture. Physiopathology and the different clinical factors involved in this type of headache are reviewed. The treatment is based in two types of procedures: those increasing cerebrospinal fluid production and those trying to decrease its leakage, like the epidural blood patch.