Clinical review: Neuromonitoring - an update.

ABSTRACT: Critically ill patients are frequently at risk of neurological dysfunction as a result of primary neurological conditions or secondary insults. Determining which aspects of brain function are affected and how best to manage the neurological dysfunction can often be difficult and is complicated by the limited information that can be gained from clinical examination in such patients and the effects of therapies, notably sedation, on neurological function. Methods to measure and monitor brain function have evolved considerably in recent years and now play an important role in the evaluation and management of patients with brain injury. Importantly, no single technique is ideal for all patients and different variables will need to be monitored in different patients; in many patients, a combination of monitoring techniques will be needed. Although clinical studies support the physiologic feasibility and biologic plausibility of management based on information from various monitors, data supporting this concept from randomized trials are still required.

Can oxidative damage be treated nutritionally?

BACKGROUND & AIMS: Nutrition and dietary patterns have been shown to have direct impact on health of the population and of selected patient groups. The beneficial effects have been attributed to the reduction of oxidative damage caused by the normal or excessive free radical production. The papers aims at collecting evidence of successful supplementation strategies. METHODS: Review of the literature reporting on antioxidant supplementation trials in the general population and critically ill patients. RESULTS: Antioxidant vitamin and trace element intakes have been shown to be particularly important in the prevention of cancer, cardiovascular diseases, age related ocular diseases and in aging. In animal models, targeted interventions have been associated with reduction of tissue destruction is brain and myocardium ischemia-reperfusion models. In the critically ill antioxidant supplements have resulted in reduction of organ failure and of infectious complications. CONCLUSIONS: Antioxidant micronutrients have beneficial effects in defined models and pathologies, in the general population and in critical illness: ongoing research encourages this supportive therapeutic approach. Further research is required to determined the optimal micronutrient combinations and the doses required according to timing of intervention.

Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study.

PURPOSE: The recent increase in drug-resistant micro-organisms complicates the management of hospital-acquired bloodstream infections (HA-BSIs). We investigated the epidemiology of HA-BSI and evaluated the impact of drug resistance on outcomes of critically ill patients, controlling for patient characteristics and infection management. METHODS: A prospective, multicentre non-representative cohort study was conducted in 162 intensive care units (ICUs) in 24 countries. RESULTS: We included 1,156 patients [mean ± standard deviation (SD) age, 59.5 ± 17.7 years; 65 % males; mean ± SD Simplified Acute Physiology Score (SAPS) II score, 50 ± 17] with HA-BSIs, of which 76 % were ICU-acquired. Median time to diagnosis was 14 [interquartile range (IQR), 7-26] days after hospital admission. Polymicrobial infections accounted for 12 % of cases. Among monomicrobial infections, 58.3 % were gram-negative, 32.8 % gram-positive, 7.8 % fungal and 1.2 % due to strict anaerobes. Overall, 629 (47.8 %) isolates were multidrug-resistant (MDR), including 270 (20.5 %) extensively resistant (XDR), and 5 (0.4 %) pan-drug-resistant (PDR). Micro-organism distribution and MDR occurrence varied significantly (p < 0.001) by country. The 28-day all-cause fatality rate was 36 %. In the multivariable model including micro-organism, patient and centre variables, independent predictors of 28-day mortality included MDR isolate [odds ratio (OR), 1.49; 95 % confidence interval (95 %CI), 1.07-2.06], uncontrolled infection source (OR, 5.86; 95 %CI, 2.5-13.9) and timing to adequate treatment (before day 6 since blood culture collection versus never, OR, 0.38; 95 %CI, 0.23-0.63; since day 6 versus never, OR, 0.20; 95 %CI, 0.08-0.47). CONCLUSIONS: MDR and XDR bacteria (especially gram-negative) are common in HA-BSIs in critically ill patients and are associated with increased 28-day mortality. Intensified efforts to prevent HA-BSIs and to optimize their management through adequate source control and antibiotic therapy are needed to improve outcomes.

The automatic selection of ventilation parameters during the initial phase of mechanical ventilation.

OBJECTIVE: To test a method that allows automatic set-up of the ventilator controls at the onset of ventilation. DESIGN: Prospective randomized crossover study. SETTING: ICUs in one adult and one children's hospital in Switzerland. PATIENTS: Thirty intubated stable, critically ill patients (20 adults and 10 children). INTERVENTIONS: The patients were ventilated during two 20-min periods using a modified Hamilton AMADEUS ventilator. During the control period the ventilator settings were chosen immediately prior to the study. During the other period individual settings were automatically determined by the ventilatior (AutoInit). MEASUREMENTS AND RESULTS: Pressure, flow, and instantaneous CO2 concentration were measured at the airway opening. From these measurements, series dead space (V(DS)), expiratory time constant (RC), tidal volume (VT, total respiratory frequency (f(tot), minute ventilation (MV), and maximal and mean airway pressure (Paw, max and Paw, mean) were calculated. Arterial blood gases were analyzed at the end of each period. Paw, max was significantly less with the AutoInit ventilator settings while f(tot) was significantly greater (P < 0.05). The other values were not statistically significant. CONCLUSIONS: The AutoInit ventilator settings, which were automatically derived, were acceptable for all patients for a period of 20 min and were not found to be inferior to the control ventilator settings. This makes the AutoInit method potentially useful as an automatic start-up procedure for mechanical ventilation.

Clinical neurophysiological assessment of sepsis-associated brain dysfunction: a systematic review.

IntroductionSeveral studies have reported the presence of electroencephalography (EEG) abnormalities or altered evoked potentials (EPs) during sepsis. However, the role of these tests in the diagnosis and prognostic assessment of sepsis-associated encephalopathy remains unclear.MethodsWe performed a systematic search for studies evaluating EEG and/or EPs in adult (¿18 years) patients with sepsis-associated encephalopathy. The following outcomes were extracted: a) incidence of EEG/EP abnormalities; b) diagnosis of sepsis-associated delirium or encephalopathy with EEG/EP; c) outcome.ResultsAmong 1976 citations, 17 articles met the inclusion criteria. The incidence of EEG abnormalities during sepsis ranged from 12% to 100% for background abnormality and 6% to 12% for presence of triphasic waves. Two studies found that epileptiform discharges and electrographic seizures were more common in critically ill patients with than without sepsis. In one study, EEG background abnormalities were related to the presence and the severity of encephalopathy. Background slowing or suppression and the presence of triphasic waves were also associated with higher mortality. A few studies demonstrated that quantitative EEG analysis and EP could show significant differences in patients with sepsis compared to controls but their association with encephalopathy and outcome was not evaluated.ConclusionsAbnormalities in EEG and EPs are present in the majority of septic patients. There is some evidence to support EEG use in the detection and prognostication of sepsis-associated encephalopathy, but further clinical investigation is needed to confirm this suggestion.

Laser therapy in pressure ulcers: evaluation by the Pressure Ulcer Scale for Healing and Nursing Outcomes Classification

AbstractOBJECTIVETo describe the pressure ulcer healing process in critically ill patients treated with conventional dressing therapy plus low-intensity laser therapy evaluated by the Pressure Ulcer Scale for Healing (PUSH) and the result of Wound Healing: Secondary Intention, according to the Nursing Outcomes Classification (NOC).METHODCase report study according to nursing process conducted with an Intensive Care Unit patient. Data were collected with an instrument containing the PUSH and the result of the NOC. In the analysis we used descriptive statistics, considering the scores obtained on the instrument.RESULTSA reduction in the size of lesions of 7cm to 1.5cm of length and 6cm to 1.1cm width, in addition to the increase of epithelial tissue and granulation, decreased secretion and odor.CONCLUSIONThere was improvement in the healing process of the lesion treated with adjuvant therapy and the use of NOC allowed a more detailed and accurate assessment than the PUSH.

A Delphi study on National PICU nursing research priorities in Australia and New Zealand.

BACKGROUND: There is a lack of evidence to direct and support nursing practice in the specialty of paediatric intensive care (PIC). The development of national PIC nursing research priorities may facilitate the process of undertaking clinical research and translating evidence into practice. PURPOSE: To (a) identify research priorities for the care of patients and their family as well as for the professional needs of PIC nurses, (b) foster nursing research collaboration, (c) develop a research agenda for PIC nurses. METHODS: Over 13 months in 2007-2008, a three-round questionnaire, using the Delphi technique, was sent to all specialist level registered nurses working in Australian and New Zealand PICUs. This method was used to identify and prioritise nursing research topics. Content analysis was used to analyse Round I data and descriptive statistics for Round II and III data. RESULTS: In Round I, 132 research topics were identified, with 77 research priorities (mdn>6, mean MAD(median) 0.68±0.01) identified in subsequent rounds. The top nine priorities (mean>6 and median>6) included patient issues related to neurological care (n=2), pain/sedation/comfort (n=3), best practice at the end of life (n=1), and ventilation strategies (n=1), as well as two priorities related to professional issues about nurses' stress/burnout and professional development needs. CONCLUSION: The research priorities identified reflect important issues related to critically ill patients and their family as well as to the nurses caring for them. These priorities can be used for the development of a research agenda for PIC nursing in Australia and New Zealand.

Vitamin C requirements in parenteral nutrition.

Some biochemical functions of vitamin C make it an essential component of parenteral nutrition (PN) and an important therapeutic supplement in other acute conditions. Ascorbic acid is a strong aqueous antioxidant and is a cofactor for several enzymes. The average body pool of vitamin C is 1.5 g, of which 3%-4% (40-60 mg) is used daily. Steady state is maintained with 60 mg/d in nonsmokers and 140 mg/d in smokers. Shocked surgical, trauma, and septic patients have a drastic reduction of circulating plasma ascorbate concentrations. These low concentrations require 3-g doses/d to restore normal plasma ascorbate concentrations, questioning the recommended PN dose of 100 mg/d. Determination of intravenous requirements is usually based on plasma concentrations, which are altered during the inflammatory response. There is no clear indicator of deficiency: serum or plasma ascorbate concentrations <0.3 mg/dL (20 micromol/L) indicates inadequate vitamin C status. On the basis of available pharmacokinetic data the 100 mg/d dose for patients receiving home PN and 200 mg/d for stable adult patients receiving PN are adequate, but requirements have been shown to be higher in perioperative, trauma, burn, and critically ill patients, paralleling oxidative stress. One recommendation cannot fit all categories of patients. Large vitamin C supplements may be considered in severe critical illness, major trauma, and burns because of increased requirements resulting from oxidative stress and wound healing. Future research should distinguish therapeutic use of high-dose ascorbic acid antioxidant therapy from nutritional PN requirements.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

OBJECTIVE: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock," published in 2004. DESIGN: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. METHODS: We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. RESULTS: Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). CONCLUSION: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

Feed the ICU patient 'gastric' first, and go post-pyloric only in case of failure.

In a randomised trial comparing early enteral feeding by gastric and post-pyloric routes, White and colleagues have shown that gastric feeding is possible and efficient in the vast majority of critically ill patients. But the authors' conclusion that gastric is equivalent to post-pyloric is true in only the least severe patients. Given the extra workload and costs, post-pyloric is now clearly indicated in case of gastric feeding failure.

Invasive Candida infections in the ICU

Invasive candidiasis, including candidemia and deep-seated Candida infections, is a severe opportunistic infection with an overall mortality in ICU patients comparable to that of severe sepsis/septic shock. With an incidence ranging from 5 to 10 cases per 1000 ICU admissions, invasive candidiasis represents 510% of all ICU-acquired infections. Although a high proportion of critically ill patients is colonised with Candida spp., only 540% develop an invasive infection. The occurrence of this complication is difficult to predict and an early diagnosis remains a major challenge. Indeed, blood cultures are positive in a minority of cases and often late in the course of infection. New non-culture based laboratory techniques may contribute to early diagnosis and management of invasive candidiasis. Recent data suggest that prediction rules based on risk factors, clinical and microbiological parameters or monitoring of Candida colonisation may efficiently identify critically ill patients at high risk of invasive candidiasis who may benefit of preventive or pre-emptive antifungal therapy. In many cancer centres, exposure to azoles antifungals has been associated with an epidemiological shift from Candida albicans to non-albicans Candida species with reduced antifungal susceptibility or intrinsic resistance. This trend has not been observed in recent surveys on candidemia in non-immunocompromised ICU patients. Prophylaxis, pre-emptive or empirical antifungal treatment are possible approaches for prevention or early management of invasive candidiasis. However, the selection of high-risk patients remains critical for an efficient management aimed at reducing the number needed to treat and thus avoiding unnecessary treatments associated with the emergence of resistance, drug toxicity and costs.

Diagnosis of invasive candidiasis in the ICU.

Invasive candidiasis ranges from 5 to 10 cases per 1,000 ICU admissions and represents 5% to 10% of all ICU-acquired infections, with an overall mortality comparable to that of severe sepsis/septic shock. A large majority of them are due to Candida albicans, but the proportion of strains with decreased sensitivity or resistance to fluconazole is increasingly reported. A high proportion of ICU patients become colonized, but only 5% to 30% of them develop an invasive infection. Progressive colonization and major abdominal surgery are common risk factors, but invasive candidiasis is difficult to predict and early diagnosis remains a major challenge. Indeed, blood cultures are positive in a minority of cases and often late in the course of infection. New nonculture-based laboratory techniques may contribute to early diagnosis and management of invasive candidiasis. Both serologic (mannan, antimannan, and betaglucan) and molecular (Candida-specific PCR in blood and serum) have been applied as serial screening procedures in high-risk patients. However, although reasonably sensitive and specific, these techniques are largely investigational and their clinical usefulness remains to be established. Identification of patients susceptible to benefit from empirical antifungal treatment remains challenging, but it is mandatory to avoid antifungal overuse in critically ill patients. Growing evidence suggests that monitoring the dynamic of Candida colonization in surgical patients and prediction rules based on combined risk factors may be used to identify ICU patients at high risk of invasive candidiasis susceptible to benefit from prophylaxis or preemptive antifungal treatment.

Mismatch of arterial and central venous blood gas analysis during haemorrhage.

BACKGROUND AND OBJECTIVE: Arterial base excess and lactate levels are key parameters in the assessment of critically ill patients. The use of venous blood gas analysis may be of clinical interest when no arterial blood is available initially. METHODS: Twenty-four pigs underwent progressive normovolaemic haemodilution and subsequent progressive haemorrhage until the death of the animal. Base excess and lactate levels were determined from arterial and central venous blood after each step. In addition, base excess was calculated by the Van Slyke equation modified by Zander (BE(z)). Continuous variables were summarized as mean +/- SD and represent all measurements (n = 195). RESULTS: Base excess according to National Committee for Clinical Laboratory Standards for arterial blood was 2.27 +/- 4.12 versus 2.48 +/- 4.33 mmol(-l) for central venous blood (P = 0.099) with a strong correlation (r(2) = 0.960, P < 0.001). Standard deviation of the differences between these parameters (SD-DIFBE) did not increase (P = 0.355) during haemorrhage as compared with haemodilution. Arterial lactate was 2.66 +/- 3.23 versus 2.71 +/- 2.80 mmol(-l) in central venous blood (P = 0.330) with a strong correlation (r(2) = 0.983, P < 0.001). SD-DIFLAC increased (P < 0.001) during haemorrhage. BE(z) for central venous blood was 2.22 +/- 4.62 mmol(-l) (P = 0.006 versus arterial base excess according to National Committee for Clinical Laboratory Standards) with strong correlation (r(2) = 0.942, P < 0.001). SD-DIFBE(z)/base excess increased (P < 0.024) during haemorrhage. CONCLUSION: Central venous blood gas analysis is a good predictor for base excess and lactate in arterial blood in steady-state conditions. However, the variation between arterial and central venous lactate increases during haemorrhage. The modification of the Van Slyke equation by Zander did not improve the agreement between central venous and arterial base excess.

Urinalysis and pre-renal acute kidney injury: time to move on.

Urinary indices are classically believed to allow differentiation of transient (or pre-renal) acute kidney injury (AKI) from persistent (or acute tubular necrosis) AKI. However, the data validating urinalysis in critically ill patients are weak. In the previous issue of Critical Care, Pons and colleagues demonstrate in a multicenter observational study that sodium and urea excretion fractions as well as urinary over plasma ratios performed poorly as diagnostic tests to separate such entities. This study confirms the limited diagnostic and prognostic ability of urine testing. Together with other studies, this study raises more fundamental questions about the value, meaning and pathophysiologic validity of the pre-renal AKI paradigm and suggests that AKI (like all other forms of organ injury) is a continuum of injury that cannot be neatly divided into functional (pre-renal or transient) or structural (acute tubular necrosis or persistent).

The 2013 Arvid Wretlind lecture: evolving concepts in parenteral nutrition.

Fifty years after the clinical introduction of total parenteral nutrition (TPN) the Arvid Wretlind lecture is an opportunity to critically analyse the evolution and changes that have marked its development and clinical use. The standard crystalline amino acid solutions, while devoid of side effects, remain incomplete regarding their composition (e.g. glutamine). Lipid emulsions have evolved tremendously and are now included in bi- and tri-compartmental feeding bags enabling a true "total" PN provided daily micronutrients are prescribed. The question of exact individual energy, macro- and micro-nutrient requirements is still unsolved. Many complications attributed to TPN are in fact the consequence of under- or over-feeding: the historical hyperalimentation concept is the main cause, along with the use of fixed weight based predictive equations (incorrect in 70% of the critically ill patients). In the late 80's many complications (hyperglycemia, sepsis, fatty liver, exacerbation of inflammation, mortality) were attributed to TPN leading to its near abandon in favour of enteral nutrition (EN). Enteral feeding, although desirable for many reasons, is difficult causing a worldwide recurrence of malnutrition by insufficient feed delivery. TPN indications have evolved towards its use either alone or in combination with EN: several controversial trials published 2011-13 have investigated TPN timing, an issue which is not yet resolved. The initiation time varies according to the country between admission (Australia and Israel), day 4 (Swiss) and day 7 (Belgium, USA). The most important issue may prove to be and individualized and time dependent prescription of feeding route, energy and substrates.