Tara Quasim

Pyridoxal Phosphate Decreases in Plasma but not Erythrocytes during Systemic Inflammatory Response

Vitamin B6 (active 3 hydroxy-2-methylpyridine derivatives) is an essential precursor of pyridoxal (PL) and pyridoxamine phosphate coenzymes of a wide variety of enzymes of intermediary metabolism (1). In plasma, pyridoxal 5′-phosphate (PLP) is the major form, whereas PLP and pyridoxamine 5′-phosphate (PMP) predominate in the cell. The most widely used method to detect vitamin B6 deficiency is the erythrocyte aspartate aminotransferase activation assay (2)(3)(4)(5). As this test is a functional rather than a direct measurement of PLP status, it may be affected by factors other than PLP deficiency (2)(3). The plasma PLP concentration is considered one of the better indicators of vitamin B6 status (1)(6)(7)(8)(9) and is reported to be well correlated with tissue PLP concentrations (8). However, vitamin concentrations in blood cells tend to be a better marker of cellular stores (10). We describe a simple, robust, reversed-phase HPLC method with precolumn derivatization using semicarbazide (11)(12)(13) that is suitable for the simultaneous measurement of PLP, 4-pyridoxic acid (PA), and PL in plasma and red cells and application of the assay in healthy individuals, patients with chronic disease, and critically ill patients requiring intensive care. Venous blood samples (EDTA) and packed red cells for population reference values were obtained from apparently healthy individuals (laboratory staff and those attending a cardiovascular risk clinic). Samples were obtained from a group of chronically ill medical and surgical patients with the potential for vitamin deficiencies (60% with short bowel syndrome and 35% with either chronic liver or renal disease) and from a critically ill group of medical and surgical patients admitted to the intensive care unit (30% with pancreatitis, 30% with trauma, 30% with organ failure). The study was approved by …

Lower concentrations of carotenoids in the critically ill patient are related to a systemic inflammatory response and increased lipid peroxidation.

BACKGROUND Critically-ill patients have low circulating concentrations of vitamin antioxidants. The functional significance of such reductions is not clear. AIMS To determine whether the presence of a systemic inflammatory response was associated with reduced circulating alpha-tocopherol and carotenoid concentrations and an increase in lipid peroxidation as evidenced by malondialdehyde. METHODS Healthy controls (n=24) and critically-ill patients (n=43) had circulating concentrations of C-reactive protein, cholesterol, triglycerides, malondialdehyde, alpha-tocopherol, lutein, lycopene, alpha- and beta-carotene measured during ITU stay. RESULTS In the critically-ill group circulating concentrations of C-reactive protein and malondialdehyde were significantly higher (P<0.05) and cholesterol, triglyceride, alpha-tocopherol, lutein, lycopene, alpha- and beta-carotene were all significantly lower (P<0.01) compared with the control group. In the critically-ill group alpha- and beta-carotene were below detection limits for many patients. After adjusting for cholesterol, lycopene concentrations remained significantly lower (P<0.001) compared with the control group. In the critically-ill patients circulating concentrations of C-reactive protein and malondialdehyde were significantly correlated (r=0.502,P<0.01). CONCLUSIONS The systemic inflammatory response is associated with increased lipid peroxidation and low carotenoid concentrations indicating that inflammation driven breakdown of carotenoids is an important factor in lowering circulating carotenoid concentrations in the critically-ill patient.

Risk of Critical Illness Among Patients With Solid Cancers: A Population-Based Observational Study

IMPORTANCE Critical illness may be a potential determinant of cancer outcomes and geographic variations, but its role has not been described before. OBJECTIVE To determine the incidence of admission to intensive care units (ICUs) within 2 years following cancer diagnosis. DESIGN, SETTING, AND PARTICIPANTS This was a retrospective observational study using cancer registry data in 4 datasets from 2000 to 2009 with linked ICU admission data from 2000 to 2011, in the West of Scotland region of the United Kingdom (population, 2.4 million; all 16 ICUs within the region). All 118,541 patients (≥16 years) diagnosed as having solid (nonhematological) cancers. Their median age was 69 years, and 52.0% were women. MAIN OUTCOMES AND MEASURES Demographic and clinical variables associated with admission to an ICU and death in an ICU. RESULTS A total of 118,541 patients met the study criteria. Overall, 6116 patients (5.2% [95% CI, 5.0%-5.3%]) developed a critical illness and were admitted to an ICU within 2 years. Risk of critical illness was highest at ages 60 to 69 years and higher in men. The cumulative incidence of critical illness was greatest for small intestinal (17.2% [95% CI, 13.3%-21.8%]) and colorectal cancers (16.5% [95% CI, 15.9%-17.1%]). The risk following breast cancer was low (0.8% [95% CI, 0.7%-1.0%]). The percentage who died in ICUs was 14.1% (95% CI, 13.3%-15.0%), and during the hospital stay, 24.6% (95% CI, 23.5%-25.7%). Mortality was greatest among emergency medical admissions and lowest among elective surgical patients. The risk of critical illness did not vary by socioeconomic circumstances, but mortality was higher among patients from deprived areas. CONCLUSIONS AND RELEVANCE In this study, about 1 in 20 patients experienced a critical illness resulting in ICU admission within 2 years of cancer diagnosis. The associated high mortality rate may make a significant contribution to overall cancer outcomes.

Rehabilitation within Scottish intensive care units: a national survey

The National Institute for Health and Clinical Excellence (NICE) in Clinical Guideline 83: Rehabilitation after critical illness has set challenging recommendations regarding the routine evaluation for, and provision of, rehabilitation within critical care units. There is no published information regarding current practice in the UK. To establish current practice in Scotland we undertook a telephone survey of all 23 Scottish ICU lead clinicians and physiotherapists − 96% of lead clinicians and 100% of lead physiotherapists completed the survey. Routine assessment for physical (median two (IQR 1–3 [range 0–4])) and non-physical sequelae (median zero (IQR 0–2 [range 0–5])) is low. Aproximately half of ICUs (52%) provide an individualised, structured rehabilitation programme, 32% include activities of daily living and all provide low intensity rehabilitation (eg limb stretching and positioning exercises). There are significant differences (all p<0.05) in the number of units routinely providing more intensive rehabilitation (eg mobilising) while patients have an endotracheal tube versus once extubated.

The incidence of intensive care unit-acquired weakness syndromes: A systematic review

We conducted a literature review of the intensive care unit-acquired weakness syndromes (critical illness polyneuropathy, critical illness myopathy and critical illness neuromyopathy) with the primary objective of determining their incidence as a combined group. Studies were identified through MEDLINE, Embase, Cochrane Database and article reference list searches and were included if they evaluated the incidence of one or more of these conditions in an adult intensive care unit population. The incidence of an intensive care unit-acquired weakness syndrome in the included studies was 40% (1080/2686 patients, 95% confidence interval 38–42%). The intensive care unit populations included were heterogeneous though largely included patients receiving mechanical ventilation for seven or more days. Additional prespecified outcomes identified that the incidence of intensive care unit-acquired weakness varied with the diagnostic technique used, being lower with clinical (413/1276, 32%, 95% CI 30–35%) compared to electrophysiological techniques (749/1591, 47%, 95% CI 45–50%). Approximately a quarter of patients were not able to comply with clinical evaluation and this may be responsible for potential underreporting of this condition.

Validation and analysis of prognostic scoring systems for critically ill patients with cirrhosis admitted to ICU

IntroductionThe number of patients admitted to ICU who have liver cirrhosis is rising. Current prognostic scoring tools to predict ICU mortality have performed poorly in this group. In previous research from a single centre, a novel scoring tool which modifies the Child-Turcotte Pugh score by adding Lactate concentration, the CTP + L score, is strongly associated with mortality. This study aims to validate the use of the CTP + L scoring tool for predicting ICU mortality in patients admitted to a general ICU with cirrhosis, and to determine significant predictive factors for mortality with this group of patients. This study will also explore the use of the Royal Free Hospital (RFH) score in this cohort.MethodsA total of 84 patients admitted to the Glasgow Royal Infirmary ICU between June 2012 and Dec 2013 with cirrhosis were included. An additional cohort of 115 patients was obtained from two ICUs in London (St George’s and St Thomas’) collected between October 2007 and July 2009. Liver specific and general ICU scoring tools were calculated for both cohorts, and compared using area under the receiver operating characteristic (ROC) curves. Independent predictors of ICU mortality were identified by univariate analysis. Multivariate analysis was utilised to determine the most predictive factors affecting mortality within these patient groups.ResultsWithin the Glasgow cohort, independent predictors of ICU mortality were identified as Lactate (p < 0.001), Bilirubin (p = 0.0048), PaO2/FiO2 Ratio (p = 0.032) and PT ratio (p = 0.012). Within the London cohort, independent predictors of ICU mortality were Lactate (p < 0.001), PT ratio (p < 0.001), Bilirubin (p = 0.027), PaO2/FiO2 Ratio (p = 0.0011) and Ascites (p = 0.023). The CTP + L and RFH scoring tools had the highest ROC value in both cohorts examined.ConclusionThe CTP + L and RFH scoring tool are validated prognostic scoring tools for predicting ICU mortality in patients admitted to a general ICU with cirrhosis.

Do alcohol use disorders impact on long term outcomes from intensive care

IntroductionThere is limited evidence regarding the impact of alcohol use disorders on long term outcomes from intensive care. The aims of this study were to analyse the nature and complications of alcohol related admissions to intensive care and determine whether alcohol use disorders impact on survival at six months post ICU discharge.MethodThis was an 18 month prospective observational cohort study in a 20 bedded mixed ICU, in a large teaching hospital in Scotland. On admission patients were allocated to one of three alcohol groups: low risk, harmful/hazardous, or alcohol dependency.Results34.4% of patients were admitted with an alcohol use disorder. Those with an alcohol related admission (either harmful/hazardous or alcohol dependent) had an increased odds of developing septic shock during their admission, compared with the low risk group (OR 1.67; 95% CI 1.13-2.47, p = 0.01). After adjustment for all lifestyle factors which were significantly different between the groups, alcohol dependence was associated with more than a twofold increased odds of ICU mortality (OR 2.28; 95% CI 1.2-4.69, p = 0.01) and hospital mortality (OR 2.43; 95% CI 1.28-4.621, p = 0.004). After adjustment for deprivation category and age, alcohol dependence was associated with an almost two fold increased odds of mortality at six months post ICU discharge (HR 1.86; CI 1.30-2.70, p = 0.001).ConclusionAlcohol use disorders are a significant risk factor for the development of septic shock in intensive care. Further, alcohol dependency is independently associated with poorer long term outcomes from intensive care.

Employment, social dependency and return to work after intensive care

Quality of life is an important measure of outcome in intensive care survivors. As return to employment is a key determinant of quality of life, we performed a prospective observational, cohort study of 75 intensive care unit patients who survived to hospital discharge. Approximately 2 years after intensive care unit discharge, 64% (18/28) of those employed before intensive care unit had returned to work. Of the rest, 10 were not working, two were unemployed, one was temporarily sick and seven were permanently sick. When health utility scores were assessed in the various employment categories, quality of life was particularly poor in the unemployed and permanently sick with median (interquartile range) scores of 0.082(−0.045−0.665) and 0.053(−0.160−0.769) respectively. Of the retired population, 95% returned to their own home with 50% requiring a family member to act as their carer. This study has demonstrated that patients who returned to work after a critical illness had a better quality of life at follow up, compared to the unemployed and permanently sick. In addition, there may be a burden on family members who act as carers for their relatives on discharge from hospital after a critical illness. Further work is required in this important area.

Caregiver strain following critical care discharge: An exploratory evaluation

OBJECTIVE The objective of this exploratory evaluation was to understand the impact of critical care survivorship on caregivers. DESIGN Family members who attended a quality improvement initiative within our critical care unit were asked to complete 4 questionnaires. SETTING The setting for this study was a 20-bedded mixed critical care unit in a large teaching hospital in Scotland. Data were collected as a part of an evaluation of a quality improvement initiative. PARTICIPANTS Thirty-six carers completed the questionnaire set. MEASUREMENTS AND MAIN RESULTS A total of 53% of caregivers suffered significant strain. Poor quality of life in the patient was significantly associated with higher caregiver strain (P= .006). Anxiety was present in 69% of caregivers. Depression was present in 56% of caregivers, with a significant association between carer strain and depression (P< .001). Those caregivers who were defined as being strained also had significantly higher Insomnia Severity Index scores than those without carers strain (P= .007). CONCLUSION This evaluation has demonstrated that there is a significant burden for caregivers of critical care survivors. Furthermore, they reported high levels of posttraumatic stress disorder, anxiety, depression, and insomnia. Future work on rehabilitation from critical care should focus on the inclusion of caregivers.

Development of Process Control Methodology for Tracking the Quality and Safety of Pain, Agitation, and Sedation Management in Critical Care Units.

Objective:To develop sedation, pain, and agitation quality measures using process control methodology and evaluate their properties in clinical practice. Design:A Sedation Quality Assessment Tool was developed and validated to capture data for 12-hour periods of nursing care. Domains included pain/discomfort and sedation-agitation behaviors; sedative, analgesic, and neuromuscular blocking drug administration; ventilation status; and conditions potentially justifying deep sedation. Predefined sedation-related adverse events were recorded daily. Using an iterative process, algorithms were developed to describe the proportion of care periods with poor limb relaxation, poor ventilator synchronization, unnecessary deep sedation, agitation, and an overall optimum sedation metric. Proportion charts described processes over time (2 monthly intervals) for each ICU. The numbers of patients treated between sedation-related adverse events were described with G charts. Automated algorithms generated charts for 12 months of sequential data. Mean values for each process were calculated, and variation within and between ICUs explored qualitatively. Setting:Eight Scottish ICUs over a 12-month period. Patients:Mechanically ventilated patients. Interventions:None. Measurements and Main Results:The Sedation Quality Assessment Tool agitation-sedation domains correlated with the Richmond Sedation Agitation Scale score (Spearman &rgr; = 0.75) and were reliable in clinician-clinician (weighted kappa; &kgr; = 0.66) and clinician-researcher (&kgr; = 0.82) comparisons. The limb movement domain had fair correlation with Behavioral Pain Scale (&rgr; = 0.24) and was reliable in clinician-clinician (&kgr; = 0.58) and clinician-researcher (&kgr; = 0.45) comparisons. Ventilator synchronization correlated with Behavioral Pain Scale (&rgr; = 0.54), and reliability in clinician-clinician (&kgr; = 0.29) and clinician-researcher (&kgr; = 0.42) comparisons was fair-moderate. Eight hundred twenty-five patients were enrolled (range, 59–235 across ICUs), providing 12,385 care periods for evaluation (range 655–3,481 across ICUs). The mean proportion of care periods with each quality metric varied between ICUs: excessive sedation 12–38%; agitation 4–17%; poor relaxation 13–21%; poor ventilator synchronization 8–17%; and overall optimum sedation 45–70%. Mean adverse event intervals ranged from 1.5 to 10.3 patients treated. The quality measures appeared relatively stable during the observation period. Conclusions:Process control methodology can be used to simultaneously monitor multiple aspects of pain-sedation-agitation management within ICUs. Variation within and between ICUs could be used as triggers to explore practice variation, improve quality, and monitor this over time.