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Clinicians can use mechanical waveform analysis as a diagnostic tool to identify pulmonary pathophysiology. This review offers an approach to develop a hypothesis of a patient’s lung pathophysiology.

Since the first recognition of a cluster of novel respiratory viral infections in China in late December 2019, intensivists in the United States have watched with growing concern as infections with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus―now named Coronavirus Disease of 2019 (COVID-19)―have spread to hospitals in the United States. Because COVID-19 is extremely transmissible and can progress to a severe form of respiratory failure, the potential to overwhelm available critical care resources is high and critical care management of COVID-19 patients has been thrust into the spotlight. COVID-19 arrived in the United States in January and, as anticipated, has dramatically increased the usage of critical care resources. Three of the hardest-hit cities have been Seattle, New York City, and Chicago with a combined total of over 14,000 cases as of March 23, 2020. In this special article, we describe initial clinical impressions of critical care of COVID-19 in these areas, with attention to clinical presentation, laboratory values, organ system effects, treatment strategies, and resource management. We highlight clinical observations that align with or differ from already published reports. These impressions represent only the early empiric experience of the authors and are not intended to serve as recommendations or guidelines for practice, but rather as a starting point for intensivists preparing to address COVID-19 when it arrives in their community.

OBJECTIVE Recombinant factor VII (rFVIIa) is used to treat cardiac surgical bleeding in an off-label manner. However, optimal dosing and timing of administration to provide efficacious yet safe outcomes remain unknown. DESIGN Retrospective, observational study. SETTING Tertiary care academic center. PARTICIPANTS Cardiac surgical patients (N = 214) who received low-dose rFVIIa for cardiac surgical bleeding. INTERVENTIONS Patients were allocated into one of three groups based on timing of rFVIIa administration during the course of bleeding resuscitation based on the number of hemostatic products given before rFVIIa administration: group one = ≤one products (n = 82); group two = two-to-four products (n = 73); and group three= ≥five products (n = 59). MEASUREMENTS AND MAIN RESULTS Patients who received low-dose rFVIIa later in the course of bleeding resuscitation (group three) had longer intensive care unit stays (p = 0.014) and increased incidence of postoperative renal failure when compared with group one (p = 0.039). Total transfusions were lowest in patients who received rFVIIa early in the course of resuscitation (group one) (median, two [interquartile range (IQR), 1-4.75]) and highest in group three (median, 11 [IQR, 8-14]; p < 0.001). Subsequent blood product transfusions after rFVIIa administration were highest in group two (p = 0.003); however, the median for all three groups was two products. There were no differences in thrombosis, reexplorations, or mortality in any of the groups. CONCLUSIONS This study identified no differences in adverse outcomes based on timing of administration of low-dose rFVIIa for cardiac surgical bleeding defined by stage of resuscitation, but the benefits of early administration remain unclear.

Delirium is associated with increased hospital costs, health care complications, and increased mortality. Long-term consequences of delirium on cognition have not been synthesized and quantified via meta-analysis.To determine if an episode of delirium was an independent risk factor for long-term cognitive decline, and if it was, whether it was causative or an epiphenomenon in already compromised individuals.A systematic search in PubMed, Cochrane, and Embase was conducted from January 1, 1965, to December 31, 2018. A systematic review guided by Preferred Reporting Items for Systematic Reviews and Meta-analyses was conducted. Search terms included delirium AND postoperative cognitive dysfunction; delirium and cognitive decline; delirium AND dementia; and delirium AND memory.Inclusion criteria for studies included contrast between groups with delirium and without delirium; an objective continuous or binary measure of cognitive outcome; a final time point of 3 or more months after the delirium episode. The electronic search was conducted according to established methodologies and was executed on October 17, 2018.Three authors extracted data on individual characteristics, study design, and outcome, followed by a second independent check on outcome measures. Effect sizes were calculated as Hedges g. If necessary, binary outcomes were also converted to g. Only a single effect size was calculated for each study.The planned main outcome was magnitude of cognitive decline in Hedges g effect size in delirium groups when contrasted with groups that did not experience delirium.Of 1583 articles, data subjected from the 24 studies (including 3562 patients who experienced delirium and 6987 controls who did not) were included in a random-effects meta-analysis for pooled effect estimates and random-effects meta-regressions to identify sources of study variance. One study was excluded as an outlier. There was a significant association between delirium and long-term cognitive decline, as the estimated effect size (Hedges g) for 23 studies was 0.45 (95% CI, 0.34-0.57; P .001). In all studies, the group that experienced delirium had worse cognition at the final time point. The I2 measure of between-study variability in g was 0.81. A multivariable meta-regression suggested that duration of follow-up (longer with larger gs), number of covariates controlled (greater numbers were associated with smaller gs), and baseline cognitive matching (matching was associated with larger gs) were significant sources of variance. More specialized subgroup and meta-regressions were consistent with predictions that suggested that delirium may be a causative factor in cognitive decline.In this meta-analysis, delirium was significantly associated with long-term cognitive decline in both surgical and nonsurgical patients.

PURPOSE: Lung protective ventilation (LPV), defined as a tidal volume (Vt) ≤8cc/kg of predicted body weight, reduces ventilator-induced lung injury but is applied inconsistently. MATERIALS AND METHODS: We conducted (1) a prospective, quasi-experimental, cohort study of adults mechanically ventilated admitted to intensive care units (ICU) in the year before, year after, and second year after implementation of an electronic medical record based LPV order, and (2) a cross-sectional qualitative study of ICU providers regarding their perceptions of the order. We applied the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) framework to evaluate the implementation. RESULTS: There were 1405, 1424, and 1342 in the control, adoption, and maintenance cohorts, representing 95% of mechanically ventilated adult ICU patients. The overall prevalence of LPV increased from 65% to 73% (p

As noted in part 1 of this series, periprocedural cardiac arrest (PPCA) can differ greatly in etiology and treatment from what is described by the American Heart Association advanced cardiac life support algorithms, which were largely developed for use in out-of-hospital cardiac arrest and in-hospital cardiac arrest outside of the perioperative space. Specifically, there are several life-threatening causes of PPCA of which the management should be within the skill set of all anesthesiologists. However, previous research has demonstrated that continued review and training in the management of these scenarios is greatly needed and is also associated with improved delivery of care and outcomes during PPCA. There is a growing body of literature describing the incidence, causes, treatment, and outcomes of common causes of PPCA (eg, malignant hyperthermia, massive trauma, and local anesthetic systemic toxicity) and the need for a better awareness of these topics within the anesthesiology community at large. As noted in part 1 of this series, these events are always witnessed by a member of the perioperative team, frequently anticipated, and involve rescuer-providers with knowledge of the patient and the procedure they are undergoing or have had. Formulation of an appropriate differential diagnosis and rapid application of targeted interventions are critical for good patient outcome. Resuscitation algorithms that include the evaluation and management of common causes leading to cardiac in the perioperative setting are presented. Practicing anesthesiologists need a working knowledge of these algorithms to maximize good outcomes.

Cardiac arrest in the operating room and procedural areas has a different spectrum of causes (ie, hypovolemia, gas embolism, and hyperkalemia), and rapid and appropriate evaluation and management of these causes require modification of traditional cardiac arrest algorithms. There is a small but growing body of literature describing the incidence, causes, treatments, and outcomes of circulatory crisis and perioperative cardiac arrest. These events are almost always witnessed, frequently known, and involve rescuer providers with knowledge of the patient and their procedure. In this setting, there can be formulation of a differential diagnosis and a directed intervention that treats the likely underlying cause(s) of the crisis while concurrently managing the crisis itself. Management of cardiac arrest of the perioperative patient is predicated on expert opinion, physiologic rationale, and an understanding of the context in which these events occur. Resuscitation algorithms should consider the evaluation and management of these causes of crisis in the perioperative setting.

Objectives To evaluate feasibility and effects of a sub-anesthetic infusion dose of ketamine versus midazolam on suicidal ideation in bipolar depression. Neurocognitive, blood and saliva biomarkers were explored. Methods Sixteen participants with bipolar depression and a Scale for Suicidal Ideation (SSI) score of ≥4 were randomized to ketamine (0.5 mg/kg) or midazolam (0.02 mg/kg). Current pharmacotherapy was maintained excluding benzodiazepines within 24 hours. The primary clinical outcome was SSI score on day 1 post-infusion. Results Results supported feasibility. Mean reduction of SSI after ketamine infusion was almost 6 points greater than after midazolam, although this was not statistically significant (estimate=5.84, SE=3.01, t=1.94, P=.074, 95% confidence interval ([CI)]=−0.65 to 12.31). The number needed to treat for response (SSI

Cardiac arrest systems of care are successfully coordinating community, emergency medical services, and hospital efforts to improve the process of care for patients who have had a cardiac arrest. As a result, the number of people surviving sudden cardiac arrest is increasing. However, physical, cognitive, and emotional effects of surviving cardiac arrest may linger for months or years. Systematic recommendations stop short of addressing partnerships needed to care for patients and caregivers after medical stabilization. This document expands the cardiac arrest resuscitation system of care to include patients, caregivers, and rehabilitative healthcare partnerships, which are central to cardiac arrest survivorship.

During pregnancy and postpartum, the risk for venous thromboembolism (VTE) is increased. A high index of suspicion is necessary to ensure the diagnosis of VTE is not missed, as the symptoms of this condition may overlap with those of pregnancy. The physiologic changes of pregnancy alter the approach to diagnosis and management of VTE. Following diagnosis, prompt initiation of anticoagulation is the cornerstone of management. For women in whom VTE is highly suspected, empiric anticoagulation treatment should be considered even prior to completion of a diagnostic evaluation. The management of pregnant and postpartum women with massive pulmonary embolism (PE) should follow the recommendations for nonpregnant patients, including administration of thrombolytics. The management of pregnant and postpartum women with both massive and submassive PE is best conducted with close multidisciplinary collaboration.

Objective Recognition of potential for neurological recovery in patients who remain comatose after cardiac arrest is challenging and strains clinical decision making. Here, we utilize an approach that is based on physiological principles underlying recovery of consciousness and show correlation with clinical recovery after acute anoxic brain injury. Methods A cohort study of 54 patients admitted to an Intensive Care Unit after cardiac arrest who underwent standardized bedside behavioral testing (Coma Recovery Scale – Revised [CRS-R]) during EEG monitoring. Blinded to all clinical variables, artifact-free EEG segments were selected around maximally aroused states and analyzed using a multi-taper method to assess frequency spectral content. EEG spectral features were assessed based on pre-defined categories that are linked to anterior forebrain corticothalamic integrity. Clinical outcomes were determined at the time of hospital discharge, using Cerebral Performance Categories (CPC). Results Ten patients with ongoing seizures, myogenic artifacts or technical limitations obscuring recognition of underlying cortical dynamic activity were excluded from primary analysis. Of the 44 remaining patients with distinct EEG spectral features, 39 (88%) fit into our predefined categories. In these patients, spectral features corresponding to higher levels of anterior forebrain corticothalamic integrity correlated with higher levels of consciousness and favorable clinical outcome at the time of hospital discharge (P = 0.014). Interpretation Predicted transitions of neocortical dynamics that indicate functional integrity of anterior forebrain corticothalamic circuitry correlate with clinical outcomes in postcardiac-arrest patients. Our results support a new biologically driven approach toward better understanding of neurological recovery after cardiac arrest.

Objectives To evaluate the association between length of ICU stay and 1-year mortality for elderly patients who survived to hospital discharge in the United States. Design Retrospective cohort study of a random sample of Medicare beneficiaries who survived to hospital discharge, with 1- and 3-year follow-up, stratified by the number of days of intensive care and with additional stratification based on receipt of mechanical ventilation. Interventions None. Patients The cohort included 34,696 Medicare beneficiaries older than 65 years who received intensive care and survived to hospital discharge in 2005. Measurements and main results Among 34,696 patients who survived to hospital discharge, the mean ICU length of stay was 3.4 days (± 4.5 d). Patients (88.9%) were in the ICU for 1-6 days, representing 58.6% of ICU bed-days. Patients (1.3%) were in the ICU for 21 or more days, but these patients used 11.6% of bed-days. The percentage of mechanically ventilated patients increased with increasing length of stay (6.3% for 1-6 d in the ICU and 71.3% for ≥ 21 d). One-year mortality was 26.6%, ranging from 19.4% for patients in the ICU for 1 day, up to 57.8% for patients in the ICU for 21 or more days. For each day beyond 7 days in the ICU, there was an increased odds of death by 1 year of 1.04 (95% CI, 1.03-1.05) irrespective of the need for mechanical ventilation. Conclusions Increasing ICU length of stay is associated with higher 1-year mortality for both mechanically ventilated and non-mechanically ventilated patients. No specific cutoff was associated with a clear plateau or sharp increase in long-term risk.

The host-microbiota relationship is integral in human health and can be rapidly disrupted in ways that may contribute to poor recovery from surgery or acute illness. We review key studies by organ system to understand the effect of perioperative and critical illness stress on the microbiota. Throughout the review, our focus is on potential interventions that may be mediated by the microbiome.Although any perioperative intervention can have a profound impact on the gut microbiota, it is less clear how such changes translate into altered health outcomes. Preoperative stress (anxiety, lack of sleep, fasting), intraoperative stress (surgery itself, volatile anesthetics, perioperative antibiotics, blood transfusions), and postoperative stress (sepsis, surgical site infections, acute respiratory distress syndrome, catecholamines, antibiotics, opioids, proton pump inhibitors) have all been associated with alterations of the commensal microflora. These factors (e.g. administration of antibiotics or opioids) can create a favorable environment for emergence of pathogen virulence and development of serious infections and multiorgan failure. Data to recommend therapies aimed at restoring a disrupted microbiota, such as probiotics/prebiotics and fecal microbiota transplants is currently scarce.The microbiome is likely to play an important role in the perioperative and ICU setting but existing data is largely descriptive. There is an expanding number of mechanistic studies that attempt to disentangle the complicated bi-directional relationship between the host and the resident microbiota. When these results are combined with ongoing clinical studies, we should be able to offer better therapies aimed at restoring the microbiota in the future.

We report a case series on the observed effects of low-dose ketamine infusions in 4 critically ill patients with varying complications related to prolonged critical illness. Doses of ketamine infusion ranged from 0.5 to 4 μg/kg/min. A low-dose ketamine infusion was used to reduce agitation in a patient requiring high doses of sedatives and analgesics. In a second patient, ketamine improved depression and anxiety symptoms. In a third patient, ketamine may have facilitated liberation from mechanical ventilation. In a fourth patient, ketamine was used for palliation to avoid lethargy. Ketamine may be considered to help decrease agitation, manage pain, facilitate opioid and benzodiazepine withdrawal, prevent respiratory depression, and potentially manage depression and anxiety in chronically critically ill patients.

This chapter describes the classic model of the circulation developed by Arthur Guyton and his team. The model envisions the circulation comprised of discrete components. The cardiac output is largely determined by the interactions of the venous return and the cardiac performance. The venous return is a function of the gradient between the mean systemic filling pressure and the right atrial pressure. The distribution of blood flow is largely controlled by autoregulation, thus matching oxygen demand and subsequently generating the venous return. Thus, cardiac output is a function of oxygen demand when cardiac function is not compromised. Caring for critically ill patient requires an understanding of Guytonian hemodynamics.

The liver transplant recipient is admitted to the intensive care unit (ICU) immediately after surgery for monitoring, resuscitation and stabilization of organ systems, management of intraoperative complications and hemodynamic pertubations, correction of coagulopathy, evaluation of graft function, and initiation of immunosuppression (Fig. 29.1). Physiological perturbations in the perioperative period affect the duration of ICU stay and may precipitate further complications and potentially multisystem organ failure (Fig. 29.2).

Pharmacotherapy to rapidly relieve suicidal ideation in depression may reduce suicide risk. Rapid reduction in suicidal thoughts after ketamine treatment has mostly been studied in patients with low levels of suicidal ideation. The authors tested the acute effect of adjunctive subanesthetic intravenous ketamine on clinically significant suicidal ideation in patients with major depressive disorder.In a randomized clinical trial, adults (N=80) with current major depressive disorder and a score ≥4 on the Scale for Suicidal Ideation (SSI), of whom 54% (N=43) were taking antidepressant medication, were randomly assigned to receive ketamine or midazolam infusion. The primary outcome measure was SSI score 24 hours after infusion (at day 1).The reduction in SSI score at day 1 was 4.96 points greater for the ketamine group compared with the midazolam group (95% CI=2.33, 7.59; Cohen's d=0.75). The proportion of responders (defined as having a reduction ≥50% in SSI score) at day 1 was 55% for the ketamine group and 30% for the midazolam group (odds ratio=2.85, 95% CI=1.14, 7.15; number needed to treat=4.0). Improvement in the Profile of Mood States depression subscale was greater at day 1 for the ketamine group compared with the midazolam group (estimate=7.65, 95% CI=1.36, 13.94), and this effect mediated 33.6% of ketamine's effect on SSI score. Side effects were short-lived, and clinical improvement was maintained for up to 6 weeks with additional optimized standard pharmacotherapy in an uncontrolled follow-up.Adjunctive ketamine demonstrated a greater reduction in clinically significant suicidal ideation in depressed patients within 24 hours compared with midazolam, partially independently of antidepressant effect.

Patients with diabetes mellitus have abnormal carbohydrate metabolism and systemic complications. Up to 10% of patients who undergo surgery present with occult diabetes mellitus. With poor glucose control, serum and tissue proteins are glycosylated to produce advanced glycosylated end products (AGEs) that contribute to the development of rapidly progressive atherosclerosis and plaque progression. AGEs block nitric oxide activity and have been implicated in the vascular complications of diabetes. The glycosylated fraction of hemoglobin (HbA1c) is formed from the nonenzymatic glycation of hemoglobin residues and reflects long-term (3 months) glucose control and may be a useful screening tool to identify patients with undiagnosed diabetes. An elevated HbA1c is associated with an increased risk of postoperative infectious complications and risk of acute kidney injury, cerebrovascular accidents, and myocardial infarction during the perioperative period. This review contains 1 figure, 2 tables, and 42 references. Key words: HbA1c, perioperative hyperglycemia, glycosylated hemoglobin, surgical infection, Diabetes Mellitus, perioperative complications

Few valid and reliable grading checklists have been published for the evaluation of performance during simulated high-stakes perioperative event management. As such, the purposes of this study were to construct valid scoring checklists for a variety of perioperative emergencies and to determine the reliability of scores produced by these checklists during continuous video review.A group of anesthesiologists, intensivists, and educators created a set of simulation grading checklists for the assessment of the following scenarios: severe anaphylaxis, cerebrovascular accident, hyperkalemic arrest, malignant hyperthermia, and acute coronary syndrome. Checklist items were coded as critical or noncritical. Nonexpert raters evaluated 10 simulation videos in a random order, with each video being graded 4 times. A group of faculty experts also graded the videos to create a reference standard to which nonexpert ratings were compared. P0.05 was considered significant.Team leaders in the simulation videos were scored by the expert panel as having performed 56.5% of all items on the checklist (range, 43.8%-84.0%), and 67.2% of the critical items (range, 30.0%-100%). Nonexpert raters agreed with the expert assessment 89.6% of the time (95% confidence interval, 87.2%-91.6%). No learning curve development was found with repetitive video assessment or checklist use. The κ values comparing nonexpert rater assessments to the reference standard averaged 0.76 (95% confidence interval, 0.71-0.81).The findings indicate that the grading checklists described are valid, are reliable, and could be used in perioperative crisis management assessment.

The paper describes HPLC, UV spectrophotometric and non aqueous titrimetric method for the estimation of poorly water soluble protease inhibitor. Ritonavir in raw material and tablet dosage form. HPLC analysis was carried out in a C18 column using acetonitrile, methanol, and buffer in the ratio 60: 20: 20 (v/v/v) at 240 nm. For the spectrophotometric determination, methanolic solution of Ritonavir was reacted with 3-methyl benzothiazolin-2-one hydrazone (MBTH). The oxidative coupled green coloured chromogen was analysed at 633 nm. Non aqueous titration was carried out using perchloric acid as titrant and the end point was determined using crystal violet as indicator. The three methods were validated and statistically evaluated to correlate the difference between the methods for estimation of Ritonavir in pharmaceutical dosage form.

Patients with liver disease have multisystem organ dysfunction that leads to physiological perturbations ranging from hyperbilirubinaemia of no clinical consequence to severe coagulopathy and metabolic disarray. Patient-specific risk factors, clinical scoring systems, and surgical procedures stratify perioperative risk for these patients. The anaesthetic management of patients with hepatic dysfunction involves consideration of impaired drug metabolism, hyperdynamic circulation, perioperative hypoxaemia, bleeding, thrombosis, and hepatic encephalopathy.

Anesthesiologists face several perioperative challenges when patients need cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion. To adequately care for these patients, anesthesiologists must understand the goals and objectives of the operation in addition to having a basic knowledge of the chemotherapeutic drugs that are frequently used. Optimal anesthetic management of patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion requires control of a complex interplay of physiologic mechanisms, including hyperthermia, abdominal hypertension, electrolyte abnormalities, coagulopathies, increased cardiac index, oxygen consumption, and decreased systemic vascular resistance. As this surgery continues to gain popularity among oncologic surgeons, further studies that clearly define the chemistry, pharmacokinetics, pharmacodynamics, and end points of efficacy need to be performed to elucidate optimal perioperative management.

OBJECTIVE We conducted this study to determine the generalizability of information gained from randomized controlled trials in critically ill patients by assessing the incidence of eligibility for each trial. DESIGN Prospective, observational cohort study. We identified the 15 most highly cited randomized controlled trials in critical care medicine published between 1998 and 2008. We examined the inclusion and exclusion criteria for each randomized controlled trial and then assessed the eligibility of each patient admitted to a study ICU for each randomized controlled trial and calculated rates of potential trial eligibility in the cohort. SETTING Three ICUs in two academic medical centers in Canada and the United States. PATIENTS Adults admitted to participating medical or surgical ICU in November 2010 or July 2011. MEASUREMENTS AND MAIN RESULTS Among the 15 trials, the most common trial inclusion criteria were clinical criteria for sepsis (six trials) or acute respiratory distress syndrome (four trials), use of invasive mechanical ventilation (five trials) or related to ICU type or duration of ICU stay (five trials). Of the 93 patients admitted to a study ICU, 52% of patients (n = 48) did not meet enrollment criteria for any studied randomized controlled trial and 30% (n = 28) were eligible for only one of the 15. Trial ineligibility was mostly due to failure to meet inclusion criteria (87% of screening assessments) rather than meeting specific exclusion criteria (52% of screening assessments). Of the positive screening assessments, 85% occurred on the first day of ICU admission. CONCLUSIONS Slightly more than half of the patients assessed were not eligible for enrollment in any of 15 major randomized controlled trials in critical care, most often due to the absence of the specific clinical condition of study. The majority of patients who met criteria for a randomized controlled trial did so on the first day of ICU admission.

Two chromatographic methods are developed and validated to estimate Atazanavir Sulfate and Ritonavir in new fixed dosage form, that is, tablet dosage form named Synthivan. The first method is based on HPLC separation of the two drugs on the reversed phase HiQSil C18 column (5 µm, 250 × 4.6 mm) at ambient temperature using an isocratic solvent system consisting of acetonitrile and water in the ratio 52:48 (v/v). Quantification is achieved with a PDA detector at 254 nm at a flow rate of 1.5 mL/min. Linearity of concentrations is found at 60–600 µg/mL and 20–200 µg/mL for Atazanavir sulfate and ritonavir, respectively. The second method is based on HPTLC separation of the two drugs on pre-coated silica gel 60F254 aluminum plates using toluene:methanol:glacial acetic acid:ethyl acetate (7:0.5:1.5:2, v/v/v/v) as solvent system followed by densitometric measurements of their spots at 254 nm. The linearity of the concentration is found to be 30–300 and 10–100 ng/spot for Atazanavir Sulfate and Ritonavir, respect...

To study the effective therapeutic bioavailability of Atazanavir Sulfate (ATV), administered singly or in combination with Ritonavir, a cost effective and rapid method is required. In order to assess an in-depth study, it is primarily thought prudent to develop an effective analytical method for estimation of ATV in marketed dosage forms. The present work is to develop a simple and precise analytical method for in depth evaluation of therapeutic efficacy of ATV. The novelty of the method shows linearity in the concentration range of 10-100 µg/mL at two wavelengths, i.e. 254 nm and 284 nm respectively. The chromatographic system consists of HiQSil C18HS column; an isocratic mobile phase consisted of methanol and tetrahydrofuran (95:5 v/v). The developed method is validated according to ICH guidelines in capsule dosage form. Validation of the developed method shows good result in range, linearity, accuracy and precision. Student’st–test was used to correlate the two methods and applied to raw materials and capsule dosage form.

Rationnelle Les patients qui ont une intervention de chirurgie vasculaire sont a plus haut risque de morbidite et de mortalite cardio-vasculaires peri-operatoire. L'index revise de risque cardiaque (IRRC) est un outil valide et couramment employe au chevet du patient pour estimer le risque d'evenement myocardique defavorable majeur peri-operatoire. Nous avons suppose que l'inclusion de l'indication pour la chirurgie ajouterait une information independante et pronostique a l'IRRC dans la prediction de la mortalite de toute cause a 30 jours et a un an lors les procedures vasculaires chirurgicales sous inguinales ouvertes. Methodes Il s'agit d'une etude retrospective de 603 patients qui ont eu une chirurgie vasculaire ouverte par pontage sous inguinal entre janvier 2002 et janvier 2008 dans un centre medical de soin tertiaire. L'IRRC et l'indication de la chirurgie etaient determines. Les criteres d'evaluation principaux etaient la mortalite de toute cause a 30 jours (incluant toute la mortalite hospitaliere, independamment du temps) et a un an. Resultats La mortalite globale a 30 jours etait de 32 (5,3%). Les facteurs de risque independants de deces precoce etaient le score IRRC, l'âge ≥80 ans, la classe 4 de statu physique de l'American Society of Anesthesiologists, et la chirurgie en urgence. La mortalite globale a un an, incluant les deces precoce, etait de 114 (18,9%). L'indication chirurgicale, le score IRRC, l'âge, la classe 4 de statu physique de l'American Society of Anesthesiologists, le sexe feminin, et la chirurgie en urgence etaient tous des facteurs predictifs independants de la mortalite a un an. Conclusions Les scores d'IRRC etaient associes a la mortalite a 30 jours et a un an chez les patients ayant une chirurgie de pontage du membre inferieur. L'indication pour la chirurgie etait predictive de la mortalite a un an mais pas de la mortalite a 30 jours.

Background Patients who undergo vascular surgery are at increased risk of perioperative cardiovascular morbidity and mortality. The Revised Cardiac Risk Index (RCRI) is a validated and widely used bedside tool for estimating the risk of a perioperative major adverse myocardial event. We hypothesized that inclusion of the indication for surgery would add independent and prognostic information to the RCRI in predicting all-cause 30-day and 1-year mortality in open infrainguinal vascular surgical procedures. Methods This was a retrospective study of 603 patients who underwent open infrainguinal bypass vascular surgery between January 2002 and January 2008 at a tertiary care medical center. RCRI and indication for surgery were determined. The primary outcomes of interest were all-cause 30-day mortality (which included all in-hospital mortality, regardless of time) and all-cause 1-year mortality. Results Overall 30-day mortality was 32 (5.3%). Independent risk factors for early death were RCRI score, being of age ≥80 years, American Society of Anesthesiologists Physical Status classification = 4, and emergency surgery. Overall 1-year mortality, including early deaths, was 114 (18.9%). Indication for surgery, RCRI score, age, American Society of Anesthesiologists Physical Status classification = 4, female sex, and emergency surgery were all independent predictors of 1-year mortality. Conclusions The RCRI score was associated with both 30-day and 1-year mortality in patients undergoing lower extremity bypass surgery. Indication for surgery was predictive of 1-year mortality but not of 30-day mortality.

In this article, the authors discuss the pharmacology of sedative-analgesic agents like dexmedetomidine, remifentanil, ketamine, and volatile anesthetics. Dexmedetomidine is a highly selective alpha-2 agonist that provides anxiolysis and cooperative sedation without respiratory depression. It has organ protective effects against ischemic and hypoxic injury, including cardioprotection, neuroprotection, and renoprotection. Remifentanil is an ultra-short-acting opioid that acts as a mu-receptor agonist. Ketamine is a nonbarbiturate phencyclidine derivative and provides analgesia and apparent anesthesia with relative hemodynamic stability. Volatile anesthetics such as isoflurane, sevoflurane, and desflurane are in daily use in the operating room in the delivery of general anesthesia. A major advantage of these halogenated ethers is their quick onset, quick offset, and ease of titration in rendering the patient unconscious, immobile, and amnestic.

Serine palmitoyltransferase (SPT) catalyzes the first committed step in sphingolipid biosynthesis. In yeast, SPT is composed of a heterodimer of 2 highly-related subunits, Lcb1p and Lcb2p, and a third subunit, Tsc3p, which increases enzyme activity markedly and is required for growth at elevated temperatures. Higher eukaryotic orthologs of Lcb1p and Lcb2p have been identified, but SPT activity is not highly correlated with coexpression of these subunits and no ortholog of Tsc3p has been identified. Here, we report the discovery of 2 proteins, ssSPTa and ssSPTb, which despite sharing no homology with Tsc3p, each substantially enhance the activity of mammalian SPT expressed in either yeast or mammalian cells and therefore define an evolutionarily conserved family of low molecular weight proteins that confer full enzyme activity. The 2 ssSPT isoforms share a conserved hydrophobic central domain predicted to reside in the membrane, and each interacts with both hLCB1 and hLCB2 as assessed by positive split ubiquitin 2-hybrid analysis. The presence of these small subunits, along with 2 hLCB2 isofoms, suggests that there are 4 distinct human SPT isozymes. When each SPT isozyme was expressed in either yeast or CHO LyB cells lacking endogenous SPT activity, characterization of their in vitro enzymatic activities, and long-chain base (LCB) profiling revealed differences in acyl-CoA preference that offer a potential explanation for the observed diversity of LCB seen in mammalian cells.

Purpose of review Heart failure and cardiovascular disease are common causes of morbidity and mortality, contributing to many ICU admissions. Nutritional deficiencies have been associated with the development and worsening of chronic heart failure. Nutritional and metabolic support may improve outcomes in critically ill patients with heart failure. This review analyzes the role of this support in the acute care setting of the ICU. Recent findings Cardiac cachexia is a complex pathophysiologic process. It is characterized by inflammation and anabolic-catabolic imbalance. Nutritional supplements containing selenium, vitamins and antioxidants may provide needed support to the failing myocardium. Evidence shows that there is utility in intensive insulin therapy in the critically ill. Finally, there is an emerging metabolic role for HMG-CoA reductase inhibition, or statin therapy, in the treatment of heart failure. Summary Shifting the metabolic milieu from catabolic to anabolic, reducing free radicals, and quieting inflammation in addition to caloric supplementation may be the key to nutritional support in the heart failure patient. Tight glycemic control with intensive insulin therapy plays an expanding role in the care of the critically ill. Glucose-insulin-potassium therapy probably does not improve the condition of the patient with heart failure or acute myocardial infarction.

Basic life support (BLS), advanced cardiovascular life support (ACLS), and post–cardiac arrest care are labels of convenience that each describe a set of skills and knowledge that are applied sequentially during the treatment of patients who have a cardiac arrest. There is overlap as each stage of care progresses to the next, but generally ACLS comprises the level of care between BLS and post–cardiac arrest care. ACLS training is recommended for advanced providers of both prehospital and in-hospital medical care. In the past, much of the data regarding resuscitation was gathered from out-of-hospital arrests, but in recent years, data have also been collected from in-hospital arrests, allowing for a comparison of cardiac arrest and resuscitation in these 2 settings. While there are many similarities, there are also some differences between in- and out-of-hospital cardiac arrest etiology, which may lead to changes in recommended resuscitation treatment or in sequencing of care. The consideration of steroid administration for in-hospital cardiac arrest (IHCA) versus out-of-hospital cardiac arrest (OHCA) is one such example discussed in this Part. The recommendations in this 2015 American Heart Association (AHA) Guidelines Update for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) are based on an extensive evidence review process that was begun by the International Liaison Committee on Resuscitation (ILCOR) after the publication of the ILCOR 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations 1 and was completed in February 2015.2 In this in-depth evidence review process, the ILCOR task forces examined topics and then generated prioritized lists of questions for systematic review. Questions were first formulated in PICO (population, intervention, comparator, outcome) format,3 and then a search strategy and inclusion and exclusion criteria were defined and a search for relevant articles was performed. The evidence was evaluated by using …

The genus Coccolithovirus is a recently discovered group of viruses that infect the globally important marine calcifying microalga Emiliania huxleyi. Surprisingly, the viral genome contains a cluster of putative sphingolipid biosynthetic genes not found in other viral genus. To address the role of these genes in viral pathogenesis, the ehv050 gene predicted to encode a serine palmitoyltransferase (SPT), the first and rate-limiting enzyme of sphingolipid biosynthesis, was expressed and characterized in Saccharomyces cerevisiae. We show that the encoded protein is indeed a fully functional, endoplasmic reticulum-localized, single-chain SPT. In eukaryotes SPT is a heterodimer comprised of long chain base 1 (LCB1) and LCB2 subunits. Sequence alignment and mutational analysis showed that the N-terminal domain of the viral protein most closely resembled the LCB2 subunit and the C-terminal domain most closely resembled the LCB1 subunit. Regardless of whether the viral protein was expressed as a single polypeptide or as two independent domains, it exhibited an unusual preference for myristoyl-CoA rather than palmitoyl-CoA. This preference was reflected by the increased presence of C16-sphingoid bases in yeast cells expressing the viral protein. The occurrence of a single-chain SPT suggested to us that it might be possible to create other fusion SPTs with unique properties. Remarkably, when the two subunits of the yeast SPT were thus expressed, the single-chain chimera was functional and displayed a novel substrate preference. This suggests that expression of other multisubunit membrane proteins as single-chain chimera could provide a powerful approach to the characterization of integral membrane proteins.