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10 EmErgEncy mEdicinE

Extracorporeal organ support in critical care: a focus on indications following injury and

possible applications in advanced medicine applications

Extracorporeal life support (EcLs) encompasses an increasingly broad range of modalities. While life support systems such as mechanical ventilation and renal replacement therapies have become more commonplace, the increasing level of complexity of patients managed in critical care settings has also increased the need for EcLs. This review highlights the most current EcLs therapies for patients with severe traumatic injuries and proposes a total extracorporeal organ support system (TEcos) as the future direction of multi-organ system life support.

by dr maureen mccunn and dr Amy J reed

– Issue N°1 – Feb./Mar. 2010

Extracorporeal support systemsEmergency perfusion resuscitation (EPR)A major cause of cardiac arrest and death fol-lowing traumatic injury is hemorrhage. Exten-sive laboratory research has led to the sugges-tion that there may be a role for extracorporeal “suspended animation” with ECLS/EPR and hypothermia following hemorrhagic cardiac arrest. Rapid induction of hypothermia with delayed resuscitation using cardiopulmo-nary bypass in laboratory animals provides a near-bloodless surgical field and often allows a good recovery.

In humans a suggested clinical indication for EPR is in patients suffering traumatic car-diac arrest from hemorrhage, with loss of vital signs on hospital admission. The EPR protocol, designed for those patients who do not immediately respond to emergent thora-cotomy, is currently in clinical trials. Follow-ing cannulation, patients are cooled with a rapid intra-aortic flush and cardiopulmonary bypass is used during delayed resuscitation and rewarming.

Extracorporeal cardiopulmonary resuscitation (ECPR)Extracorporeal cardiopulmonary resuscita-tion (ECPR) following cardiac arrest is the most rapidly increasing indication for ECLS. A recent review from the Extracorporeal Life Support Organization reported that 11% of the use of ECLS for ECPR in adults was with cases of cardiac arrest. In these patients, there was a statistically significant trend towards decreased survival with increased length of treatment. Survival to hospital discharge was 27%, but 33% of patients suffered neurological sequela (seizure, intracranial bleeding, stroke or brain death).

Extracorporeal membrane oxygenation (ECMO)ECMO is often the only option when mechani-cal ventilation fails to achieve adequate oxy-genation and/or carbon dioxide exchange. The CESAR (Conventional Ventilation or ECMO for Severe Adult Respiratory Failure) trial eval-uated ECMO versus conventional ventilation for severe respiratory failure. Of the patients who received ECMO, 57 of 90 met the primary endpoint of survival or absence of severe dis-ability at six months compared with 41 of 87 patients in the conventional ventilation group. This translated to a relative risk in favor of the

ECMO group of 0.69, suggesting early ECMO intervention may be beneficial.

Concern over the use of ECMO following trauma is not supported by the literature. A case series from 2004 -2007 reports on nine patients with post-traumatic acute respiratory distress syndrome (ARDS) who had failed conventional therapies. Of these, seven patients (77.8%) were weaned and discharged. Clinicians in Germany have also had recent success with VA ECMO in treating ARDS following severe chest injury in poly-traumatized patients.

Use of a pumpless extracorporeal circuit has been recently reviewed, which has the advan-tage of being simple and efficient. This allows for easier intra-hospital, inter-hospital and even international transport. Weaning was suc-cessful in 52.2% of patients and overall 33.1% of patients survived to hospital discharge. There are technical hemodynamic limitations imposed by this system due to an arteriovenous shunt intrinsic in the circuit, although a pump can be added into the circuit and VA ECMO, with flow reversal through the cannulas. This system has applications for military field use and as a ‘bridge’ to definitive resuscitation.

Despite the need for specialized equipment and practitioners, a recent study series suggest that even hospitals with limited experience may have good results following ECLS. Usage of this treatment modality is further expanded by data supporting inclusion of patient popu-lations who were previously excluded (e.g. based on age).

Renal replacement therapyAcute kidney injury (AKI) or exacerbation of existing renal dysfunction is a common sequela of traumatic injury. Additionally, AKI can lead to lung damage via cellular and solu-ble mediators. Acute lung injury (ALI) in turn, facilitates and exacerbates kidney dysfunction via metabolic and biomechanical derange-ments and may also lead to the production of factors that may be renally cytotoxic. In situations where AKI and ALI are combined, mortality exceeds 80%. Therefore the impetus exists to treat AKI, but when to initiate renal replacement therapy (RRT), what ‘dose’ to pre-scribe, and if these strategies improve survival remain debatable.

Figure I. Conceptual schematic of a TECOS (total extracorporeal organ support) system. Blood initially flows through a hemofilter for renal solute clearance

and an albumin/adsorption filter mimicking liver puri-fication. Fraction of flow to each filter could theoreti-cally be adjusted to achieve desired clearance rates.

All blood then flows through the oxygenator (with sweep gas for CO2 clearance as needed) then back

to the patient through either an arterial or venous return line. Image reproduced courtesy of Wolters

Kluwer Health

Liver

OxygenatorK

i

d

n

e

y

Dialysate

11 – Issue N°1 – Feb./Mar. 2010

The data supporting early RRT in patients following trauma are limited to small studies. In combat settings, the development and use of dialysis decreased mortality from renal failure through the 1970s, but no overall change in mortality has been demonstrated since. An extensive report of dialysis use in recent military conflicts highlights the need for port-able, easy-to-use systems. In a small study examining burn patients with AKI, CRRT lowered both 28-day and in-hospital mortality. Further-more, design improvements such as larger pore sizes filters and antibi-otic-coated fibers show encouraging results in preliminary studies, and should further expand the applications for CRRT.

Finally, extensive experience has shown that RRT can be used safely in trauma patients without affecting systemic coagulation parameters. A case report of CRRT initiated for refractory intracranial hyperten-sion following traumatic brain injury (TBI) was recently published. The removal of fluids, solutes and inflammatory cytokines correlated with decreased intracranial pressure in the patient without deleterious coagulopathic sequela.

Liver dialysisConventional hemofiltration and hemodialysis techniques are insuffi-cient to clear albumin-bound toxins present in the setting of liver fail-ure. Direct charcoal hemoperfusion and albumin-dialysis detoxification systems remove albumin-bound (bilirubin and bile acids) and water-soluble toxins. Liver dialysis decreases levels of nitric oxide, cytokines (TNF-alpha, IL-6, IL-8 and interferon gamma) and lowers mortality in acute-on-chronic liver failure. Large randomized trials are currently underway, but each of the commercially available systems (e.g. MARS) has demonstrated benefit in small preliminary trials. However, in trauma patients, this therapy remains at the level of case reports.

Extracorporeal brain supportIt is now recognized that non-neurological organ dysfunction is com-mon in patients with severe TBI and is independently associated with worse outcome. Respiratory failure is the most common, followed by cardiovascular failure. Failure of the coagulation and renal systems has also been seen. Therefore, the need to support organ systems following severe neurological injury should be anticipated.

There is currently no brain ‘dialysis’ system in clinical use for neurologi-cal injury or failure, but new laboratory findings support the develop-ment of such a system. In an animal model study of TBI, dialysis on the brain surface (following a decompressive craniectomy) with a semi-permeable membrane allowed water and small molecules to move from the damaged brain surface across the dialysis membrane into the osmotic chamber, rather than into brain, resulting in significantly lower CSF pressures.

Traumatic brain injury is often cited as a contraindication for the clini-cal use of ECLS, despite reports of good neurological outcomes in these patients. Two recent case reports describe the use of ECLS in this patient population and challenge this belief. Acute cardiopulmonary fail-ure associated with increased ICP, resulting from severe TBI, has been successfully treated with ECLS at both a U.S. and a Taiwanese trauma center with full neurological recovery in both cases.

Evolution of extracorporeal supportIndications for ECLS have broadened to include nearly all organ systems. The severity of patient diseases and the imagination of healthcare pro-viders have progressed more rapidly than has the available technology, limiting clinical use of these circuits to more technologically advanced institutions. Fortunately, recent advances that broaden both the treat-ment base and systems development continue to move the field forward. Systems that were initially crude and used only as terminal treatment

efforts, such as dialysis and mechanical ventilation, are now used rou-tinely in operating rooms, ICUs, rehabilitation facilities and even in homes. Extracorporeal systems have matured from the lab to the bed-side, from the OR to the ICU, and have the potential to travel across the world. The future of extracorporeal support will likely involve both refinement of existing materials (i.e. biomembranes) and techniques, as well as development of novel ones (i.e. nanotechnology).

Since our patients present with multiple organ failure, one must consider multiple organ support. We hereby suggest the concept of a single ‘organ support’ machine to be brought to and travel with the patient, initiated as therapy prior to the patient developing multiple-organ failure. Such a total extracorporeal organ support (TECOS) system would derive indi-vidual subunits from current ECLS modalities (see figure), thereby sup-porting multiple organ systems, as necessary, through a single cannula-tion strategy. There is clear support for the use of ECMO in patients with multiple organ dysfunction. Inasmuch as patients treated with ECPR often develop organ dysfunction, i.e. lungs and/or kidneys, they could potentially benefit from modalities aimed at these organ systems. Treat-ment of acute liver failure with extracorporeal support has been shown to improve survival, and as such would be an important component of

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a multi-modal strategy. ECLS, although often initiated for single organ dysfunction, may also support the hematologic, coagulation and central nervous organ systems, among others.

TECOS could also be used as a nontraditional bridge to transplant. Most donations after car-diac death (DCD) of organs for transplantation are obtained from patients following traumatic injury. Implementation of a DCD protocol using extracorporeal perfusion has been shown to increase both the number of viable organs as well as individual graft function, resulting in an overall shorter duration of hospital stay. TECOS could theoretically provide multi-organ support for this endeavor, maximizing utility of single patient donation.

Extracorporeal modalities can be life-saving interventions in the critically ill and injured. Through their continued evolution as technol-ogy advances, the real challenges that persist will be to determine the indications and con-traindications for individual patients, and the appropriate timing for initiation and withdrawal.

Background readingAnderson HL 3rd, Shapiro MB, Delius RE et al. Extracorporeal life support for respiratory failure after multiple trauma. J Trauma. 1994; 37: 266-272.Bakhtiary F, Keller H, Dogan S et al. Venoarterial extracorporeal membrane oxygenation for treat-ment of cardiogenic shock: Clinical experiences in 45 adult patients. Journ Thor and Cardiovas Surg 2008; 135: 382 – 388.Flörchinger B, Philipp A, Klose A et al. Pumpless extracorporeal lung assist: a 10-year institutional experience. Ann Thorac Surg 2008; 86: 410 – 417.

Stadlbauer V, Krisper P, Aigner R, Haditsch B, Jung A, Lackner Honore PM, Joannes-Bovau O, Merson L et al. The big bang of hemofiltration: the beginning of a new era in the third millennium for extracor-poreal blood purification! Int J Artif Organs 2006; 29: 649 – 659.Huang YK, Liu KS, Lu MS et al. Extracorporeal life support in post-traumatic respiratory distress patients. Resuscitation 2009; 80: 535 – 539. Liu JP, Gluud LL, Als-Nielsen B et al. Artificial and bioartificial support systems for liver failure. Cochrane Database Syst Rev 2004; 1:CD003628.Madershahian N, Wittwer T, Strauch J et al. Applica-tion of ECMO in multitrauma patients with ARDS as rescue therapy. J Card Surg 2007; 22: 180 – 184.Marasco SF, Lukas G, McDonald M et al. Review of ECMO (extracorporeal membrane oxygenation) support in critically ill adult patients. Heart, Lung and Circ 2008; 17S: S41-S47.McCunn M, Reynolds HN, Reuter J et al. Continu-ous renal replacement therapy in patients follow-ing traumatic injury. Int J Artif Organs 2006; 29: 166 - 186. Michaels AJ, Schriener RJ, Kolla S et al. Extracorpor-eal life support in pulmonary failure after trauma. J Trauma 1999;46:638-645.Phua J, Lee KH. Liver support devices. Curr Opin Crit Care 2008; 14: 208 – 215.Ricci Z, Ronco Cm D’Amico G et al. Practice pat-terns in the management of acute renal failure in the critically ill patient: an international survey. Nephrol Dial Transplant 2006; 21: 690- 696.Thiagarajan RR, Brogan TV, Scheurer MA. Extracor-poreal membrane oxygenation to support cardiop-ulmonary resuscitation in adults. Ann Thorac Surg 2009; 87: 778 – 785.VA/NIH Acute renal failure network: Intensity of renal support in critically ill patients with acute

kidney injury.Zygun DA, Klortbeek JB, Fick GH et al. Non-neu-rologic organ dysfunction in severe traumatic brain injury. Crit Care Med 2005; 33: 654 – 660.

The authorsMaureen McCunn, MD, MIPP, FCCMAmy J Reed, MD, PhDDepartment of Anesthesiology and Critical Care MedicineUniversity of Pennsylvania School of MedicineUSA

Correspondence to:Maureen McCunn, MD, MIPP, FCCMDepartment of Anesthesiology and Critical Care MedicineUniversity of Pennsylvania School of Medicine3400 Spruce Street, Dulles 6Philadelphia, Pennsylvania [email protected]

Note: The full version of this overview has been previously published: McCunn M, Reed AJ, Critical care organ sup-port: a focus on extracorporeal systems. Curr Opin Crit Care. 2009; 15: 554-559.

AcknowledgementsHN Reynolds, MD, and Karen A. McQuillan, RN, MS, CCRN, CNRN, for design assistance; Robert H. Bartlett, MD for manuscript review.

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12 EmErgEncy mEdicinE – Issue N°1 – Feb./Mar. 2010

Second study supports use of NGAL test for early identification of acute kidney injury in critically ill patientsAccording to a recent study published in Inten-sive Care Medicine [1], a novel bedside blood test carried out in critically ill patients being admitted to the intensive care unit can help to identify which patients are at risk of acute kidney injury (AKI). The study carried out in

Vicenza, Italy, involved the testing of blood samples collected during admission to the ICU. The test were carried out using the Triage NGAL Test, a product currently sold by Inverness Medical Innovations, Inc. outside of the United States.

AKI is a common and often devastating complication for up to 25% of critically ill patients admitted to the ICU and can lead to a significant increase in hospital length of stay and associated costs. Also associ-ated with an increased risk of death, AKI is often detected too late into its clinical progression when a substantial portion of kidney function may already have been lost and the window for initiating treatment to

prevent further harm has closed. A small study conducted in early 2009 at the University Hospital of Clermont-Ferrand, France and published in the Journal of Critical Care [2] found that a new bedside blood test for a blood biomarker called neutrophil gelatinase-associated lipocalin (NGAL) offered the promise of rapidly assessing if a critically ill patient is suffering from AKI. Now results from the prestigious Department of Nephrology at San Bortolo Hospital in Vicenza Italy have confirmed these findings in a larger study published in Intensive Care Medicine [1]. In this study of 301 critically ill patients, plasma NGAL measured with the Triage NGAL Test was a statistically significant diagnostic marker of AKI development within the next 48 hours (area-under-ROC 0.78), and for renal replacement therapy use (area-under-ROC 0.82). Moreover, peak plasma NGAL concentrations increased with worsening AKI severity (R=0.554, p<0.001).

1. Cruz DN et al. Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population. Intensive Care Med. 2009 Dec 3.

2. Constantin JM et al. Plasma neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in adult critically ill patients: A prospective study. J Crit Care. 2009 Sep 23.

Assessment and monitoring A history of intensive care admission is a well documented indicator of subsequent near fatal asthma. In a study of asthma patients admit-ted with a near fatal episode, two thirds of subsequent severe attacks or deaths occurred within one year of the previous life-threating admission [4].

The immediate assessment of patients with asthma should include the degree of respira-tory distress (ability to speak, respiratory rate, use of accessory muscles, air entry), degree of hypoxia (cyanosis, pulse oximetry, level of consciousness) and cardiovascular stabil-ity (arrhythmias, blood pressure). Accessory muscle use, wheeze, paradox and tachypnoea may diminish with patient fatigue [5]. It should

be noted that the clinical examination may be misleading. Asthmatics with poor per-ception of the severity of their asthma may appear deceptively well, despite significant decrements in lung function [6].

While the assessment relies on clinical signs, additional information may be obtained from chest radiography or blood gas analy-sis, but neither should delay the initia-tion of appropriate therapy. An episode of acute asthma is characterized by hyper-inflation of the lungs on chest radiogra-phy. Abnormalities in pulmonary function tests include markedly decreased FEV1 or peak expiratory flow rate. Blood gas analy-ses may demonstrate respiratory alkalosis, hypoxaemia and hypocarbia. Asthmatic

episodes are generally not characterized by marked arterial desaturations until late in the episode. Normocarbia should be considered as impending respiratory failure requiring aggressive treatment [7].

Patients who fail to respond to therapy (PEFR improved by less than 10–20%) or with per-sistent hypercapnia, tachypnoea (respiratory rate > 30), altered mental status, arrhythmias or significant comorbidities should be referred to the ICU [3]. The wide range of potential complications needs to be considered when managing severe asthma.

TherapyThe goals of therapy are the maintenance of oxygenation, relief of airflow obstruc-tion, reduction of airway oedema and mucus plugging, while supporting ventilation as clinically indicated.

OxygenIn asthma hypoxaemia results from ventila-tion/perfusion mismatching and is usually modest. Treatment should be based on achiev-ing target oxygen saturations > 92%, rather than giving predetermined concentrations of inspired oxygen. Inspired oxygen must be humidified to prevent the bronchoconstrictive effect of dry gas.

b2 AgonistsShort-acting, rapid onset inhaled β2-agonists are the drugs of choice for treating acute asthma, salbutamol being the most frequently used. In acute severe asthma, salbutamol may be administered either by nebulisation or repeated activations of a metered dosed inhaler (MDI) via a large volume spacer. How-ever, data comparing the two modes of drug delivery in severe asthma exacerbations are lacking. If the prior use of an MDI has been inadequate, nebulised aerosolisation may be advantageous [8]. β2-agonists may be delivered by bolus (inter-mittent) versus continuous nebulisation, the latter being distinctly different from ‘back-to-back’ nebulisation. The continuous method involves the use of adapted systems to deliver larger quantities of the same bronchodilator agent over a number of hours (e.g. salbuta-mol at a rate of 10–20 mg/h). A systematic review of randomised controlled trials of acute asthma in adults failed to identify any significant differences in lung function or hos-pital admission rates between the continuous and intermittent methods [9]. Intravenous

management of acute severe asthmaAcute severe asthma is challenging for the clinician with respect to recognition and appropriate management. currently, asthma accounts for between 1.7% and 2.0% of all icU admissions [1]. near-fatal asthma (nFA) is defined as acute asthma associated with a respiratory arrest or arterial carbon dioxide tension greater than 50 mm Hg, with or without altered consciousness [2]. There are two phenotypes of near-fatal asthma. The most common is responsible for 80–85% of all fatal events. it is characterized by eosinophilic inflammation associated with gradual deterioration over days or weeks occurring in patients with severe, poorly controlled asthma, and is slow to respond to therapy. The second phenotype, with neutrophilic inflammation, has both a rapid onset and response to therapy [3].

by dr Anthony Holley and dr robert Boots

13EmErgEncy mEdicinE – Issue N°1 – Feb./Mar. 2010

Table I. Clinical markers of severe asthma.

Inability to speak in full sentences1. Use of accessory muscles or tracheal tugging2. Quiet chest on auscultation3. Patient seated upright and unable to lie supine4. Cyanosis and sweating5. Confusion or decreased level of consciousness6. Hypotension or bradycardia7. FEV8. 1 < 40%, predicted or PEF < 40% of best or predicted (<25% in life-threatening asthma)Oxygen saturations < 90-92%9. PaO10. 2 < 60 mmHgPaCO11. 2 > 45 mmHgPulsus paradoxus (> 15 mmHg decrease with inspiration). With severe muscle 12. fatigue may be absent

FEV1 = forced expiratory volume in the first secondPEF = peak expiratory flow(adapted from reference 1)

β2-agonists have been described as rescue therapy for use in patients unresponsive to inhaled bronchodilator and systemic corti-costeroid therapy, or when the inhaled route is not practical [10].

AdrenalineAdrenaline has been administered both by nebulisation and intravenously. There are theoretical advantages to the use of intra-venous adrenaline in acute severe asthma, as opposed to using pure β2 agonists. The alpha effect of adrenaline may be benefi-cial in decreasing airway oedema, while the beta effect provides for bronchodilation. With respect to adrenaline infusions, their use would be reasonable as a rescue therapy in critical asthma, particularly if associated with hypotension not secondary to dynamic hyperinflation [11].

Ipratopium bromideAnticholinergics agents block muscarinic receptors in airway smooth muscles, inhibit vagal cholinergic tone and result in bronchodil-atation. Ipratropium bromide has a mild addi-tional bronchodilating effect when added to ß agonists that may only be significant in severe asthma [12]. The combination of ipratropium bromide with a β2-agonist has been shown to be superior to a β2 agonist alone [13].

CorticosteroidsCorticosteroids have been shown to improve asthma symptoms by reducing airway inflam-mation, airway reactivity, airway secretions and restoring the integrity of the airways. Additional to their anti-inflammatory effect,

steroids increase both the number and sensi-tivity of β-receptors on the bronchial smooth muscle [14,15]. Since the benefits of corticos-teroid treatment are not usually seen until 6–24 h after administration, therapy should be instituted early. Oral and intravenous routes of corticosteroid administration are equally efficacious [16]. There is some suggestion that for patients with severe symptoms, intra-venous corticosteroid therapy may have an early effect (within 1 to 6 hours) by reversing β2-receptor down regulation seen in chronic β2-agonist use [17].

AminophyllineThe use of intravenous aminophylline as a routine agent in the treatment of acute asth-matic patients has declined in the past few years. A Cochrane review [18] failed to show any evidence of benefit of aminophylline, especially in severe asthma, and is associated with more adverse effects. Whether amino-phylline has a place as an additional therapy after treatment with established medications remains uncertain.

Magnesium sulphateMagnesium may be effective in acute asthma through relaxation of smooth muscle and inhibition of smooth-muscle contraction. Magnesium is involved in acetylcholine and histamine release from cholinergic nerve terminals and mast cells, respectively. The ability of magnesium to block the calcium-ion influx into the bronchial smooth muscle may have therapeutic benefit in severe acute asthma [19]. Magnesium is safe, inexpensive and has shown benefit in the severe asthmatic subgroup and therefore its use in this setting would seem appropriate [20].

8. HelioxHelium/oxygen mixtures have the potential to decrease airway resistance secondary to their lower density with respect to air (80% helium/20% oxygen mixture has a density approximately one third that of air). It decreases the work of breathing in situations of increased airway resistance. Heliox may improve pulmo-nary function in more severe asthmatics, is safe, well tolerated but at this point rquires further validation of benefit [21].

Anaesthetic volatilesPatients with severe bronchospasm requiring mechanical ventilation and not responding to conventional bronchodilator therapy may benefit from an inhaled volatile anaesthetic agent with bronchodilating properties such as enflurane or isoflurane [22-26].

AntibioticsThere is no benefit to the routine use of antibiotics unless bacterial infection is likely [27].

VentilationDespite appropriate therapy, there continues to be a small group of patients who deteriorate or those who present in extremis and require mechanical ventilation. The rate of intubation in patients with acute severe asthma is low at 3-8 % [28].

Non invasive ventilationSurprisingly only a few reports have described the use of non invasive ventilation (NIV) in patients with acute severe asthma. A Cochrane review performed in 2005 concluded that there are promising results in favour of the use of NIV in severe acute asthma. However, the regular use of NIV in status asthmaticus still remains controversial in the absence of large randomised controlled trials [29].

Invasive ventilationDeteriorating consciousness, severe exhaustion and cardiopulmonary arrest are absolute indi-cations for intubation and mechanical ventila-tion. Severe hypercapnia, acidosis and fatigue may not warrant immediate intubation, but rather aggressive and continuous bronchodila-tor therapy. Intubation and mechanical ventila-tion in the asthmatic should not be embarked upon lightly. The optimal means of intubation is usually direct laryngoscopy, following rapid sequence induction. The best agents to use are those most familiar to the operator. Induction may effectively be achieved with propofol or thiopentone, however careful dosage adjust-ment is required for potential haemodynamic compromise. The asthmatic patient is often volume depleted, with induction resulting in both loss of sympathomimetic tone and drug induced vasodilation. Additional to this, the development of intrinsic PEEP with an

14 EmErgEncy mEdicinE – Issue N°1 – Feb./Mar. 2010

Table 2. Asthma complications, adapted from Restrepo & Peters [3].

Pneumothorax1. Pneumomediastinum2. Pneumopericardium3. Pulmonary interstitial 4. emphysemaPneumoretroperitoneum5. Cardiac arrhythmias6. Myocardial ischaemia or 7. infarctionMucus plugging8. Atelectasis9. Pneumonia10. Electrolyte disturbances 11. (hypokalaemia, hypomagnesaemia, hypophosphataemiaLactic acidosis12. Hyperglycaemia13. Theophylline toxicity14.

Table 3. Initial ventilator settings in paralysed asthmatic patients (adapted from

Phipps and Garrard [28]).

Initial ventilator settings in

paralysed asthmatic patients

1. FiO2 1.0, then titrate to keep

SpO2 > 94%

2. Tidal volume 5-6 ml/kg

3. Ventilator rate 6-8 breaths/minute

4. Long expiratory time

(I:E ratio > 1:2)

5. Minimal PEEP < 5 cmH2O

6. Limit peak inspiratory pressure to

< 40 cmH2O

7. Target Plateau pressure

< 30 cmH2O

8. Ensure effective humidification

15

inappropriate ventilation strategy, may rapidly result in catastrophic circulatory collapse. In this regard ketamine with its sympathomi-metic and bronchodilating prop-erties has been advocated by many as the induction agent of choice [30]. The usual dose of ket-amine for intubation is 1-2 mg/Kg given intravenously over two minutes. Suxamethonium may be used safely to achieve rapid paralysis for intubation, but the known complications need to be considered. Following induction, maintaince with fentanyl and midazolam is appropriate.

On-going paralysis may initially be required to facilitate ventilation, however because of the significant risk of critical care neuromyopa-thy, (especially given the combina-tion with steroids) neuromuscular blockade should be withdrawn as soon as possible [31].

Ventilation strategyThe mode of ventilation may be a crucial factor for success-ful outcome of near-fatal asthma. Mechanical ventilation is difficult because of the combination of severe restrictive and obstructive defects. The obstructive defect may result in dynamic hyperinflation. This may then lead to barotrauma, volutrauma or catastrophic haemo-dynamic compromise secondary to impairment of venous return [7]. It is the practice of the authors to initially hand-bag asthmatic patients following intubation. This allows for an assessment of sever-ity of bronchospasm and for a slow rate of 4-5 breaths per minute and avoids dynamic hyperinflation [32]. Once the situation is consid-ered stable an attempt to mechani-cally ventilate the patient is made. Regardless of the mode of ventila-tion selected, mechanical ventila-tion in near-fatal cases should aim to maintain adequate oxygenation, minimize dynamic hyperinflation, avoid barotrauma and allow some degree of permissive hypercapnia until bronchodilators and ster-oids improve airflow. Outcome is improved in mechanically venti-lated asthmatics by limiting air-way pressure using a low respira-tory rate and tidal volume while permitting a moderate degree

of hypercarbia and respiratory acidosis [33].

ConclusionAcute severe asthma remains a significant clinical problem, which requires early identification to facilitate appropriate therapeutic interventions. An understanding of the available agents and poten-tial pitfalls in the management of near fatal asthma is mandatory for the emergency physician.

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30. Hemming A, MacKenzie I, Finfer S. Thorax 1994; 49:90-91

31. Griffin D et al. Chest 1992; 102:510-514

32. Holley A, Boots R. Emergency Medicine Australasia. 2009 Aug;21(4):259-68

33. Darioli R, Perret C. Am Rev Respir Dis 1984; 129:385-387

The authorsAnthony Holley BSc. MBBCh. DipPaeds. DipDHM. FACEM. FJFICMStaff Intensivist and Robert Boots, M.D.

Department of Intensive Care Medicine,Royal Brisbane & Women’s HospitalHerston QLD 4029 Australia


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New SBI and ACR recommendations suggest breast cancer screening should begin at age 40The new recommendations from the Society of Breast Imaging (SBI) and the American College of Radiology (ACR) on breast cancer screening, published in the January issue of the Journal of the American College of Radiology (JACR), state that breast cancer screening should begin at age 40, and earlier in high-risk patients. The recommendations also suggest appropriate uti-lization of medical imaging modalities such as mammography, MRI and ultrasound for breast cancer screening. According to Dr Carol Lee the significant decrease in breast cancer mortal-ity is a major medical success and is due largely to earlier detection of breast cancer through mammography screening. For women with the highest risk of developing breast cancer, screen-ing technologies in addition to mammography have been adopted. The new recommendations include screening for breast cancer by mam-mography, MRI and ultrasound as well as con-sidering risk factors. The average patient should begin annual breast cancer screening at age 40. High-risk patients should begin by age 30 but not before 25. According to Dr Lee, evidence to sup-port the recommendation for regular periodic screening mammography comes from the results of several randomized trials (RCTs) conducted in Europe and North America that included a total of nearly 500,000 women. Overall, based on a meta-analysis of the RCTs, there was a 26 per-cent reduction in mortality. Mammography was the only imaging modality that had been proven to decrease mortality from breast cancer.www.jacr.org/

NIH takes step to assess any possible risk associated with low-dose radiation exposureResearchers at the National Institutes of Health (NIH) Clinical Center, USA, are incorporating radiation dose exposure reports into patients’ elec-tronic medical records, an effort that they hope will lead to an accurate assessment of whether any cancer risk is associated with low-dose radiation exposure from medical imaging tests, according to an article in the February issue of the Journal of the American College of Radiology (JACR). The electronic medical record allows for the storage, retrieval and manipulation of medical records. There is much controversy surrounding diagnos-tic medical radiation exposure. According to Dr David Bluemke, lead author of the article, one widely publicized appraisal of medical radiation exposure suggested that about 1.5 to 2 percent of all cancers in the USA might be caused by the

clinical use of CT alone. Since there are no epide-miological data directly relating CT scanning to cancer deaths, scientific assessment must instead rely on the relationship between radiation expo-sure and death rates from Japanese atomic bomb survivors. Radiology and nuclear medicine at the NIH Clinical Center have developed a radiation reporting policy. All vendors who sell imaging equipment to will be required to provide a routine means for radiation dose exposure to be recorded in the electronic medical record. This require-ment will allow cataloging of radiation exposures from these medical tests. In addition, radiation exposure will have to be tracked by patients in their own personal health record. This approach is consistent with the ACR and RSNA stated recommendation, that “patients should keep a record of their X-ray history.”www.jacr.org/

New CATCH rule to determine need for CT scans in children with minor head injury

A new tool may help standard-ize the use of CT scans in chil-dren with minor head injury and help reduce the number of scans, according to a

new study published in the Canadian Medical Association Journal.More than 650,000 children with minor head injuries resulting in loss of consciousness, amne-sia, disorientation and/or vomiting are seen each year in emergency departments at North American hospitals. CT scans are important for diagnosing serious brain injuries but they expose children to the potentially harmful effects of ionizing radiation and significantly add to health care costs. A team of researchers from pediatric institutions across Canada have developed the CATCH rule (Canadian Assessment of Tomography for Child-hood Injury) to guide physicians in determining whether a child with minor head trauma should receive a CT scan. The study involved 3866 chil-dren aged 0 to 16 years of age from 10 Canadian pediatric teaching institutions. The authors of the study conclude that the CATCH Rule, made up of 7 simple findings from the child’s history and physical exam, has the potential to both stand-ardize the need for CT and reduce the number of CT scans performed in children with minor head injury. www.cmaj.ca/

Contrast enhanced ultrasound imaging:

is it safe?Page 18 - 21

Risks associated with exposure to low-dose radiation in women with a genetic predisposition

to breast cancerPage 22 - 23

Detection and diagnosis of breast cancer with novel magnetic resonance

imaging techniquesPage 24 - 26

February / March 2010

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18 mEdicAL imAging

IntroductionStabilised gas-filled microbubbles provide imag-ing contrast in some diagnostic ultrasound applications. They provide extra scattering cen-tres that may improve visualization of the vas-culature and of blood filled spaces such as the heart [1]. However, their intra-venous injection increases the potential of the hazard associated with gas bodies in tissues exposed to ultrasound. A “hazard” is defined as a possible source of harm, while “risk” is the probability of occurrence of harm and “safety” is the absence of unaccept-able risk [2]. In performing a contrast enhanced ultrasound scan, the ratio of the risk taken to the benefit gained must be taken into account. This can be only be properly assessed from available experimental and clinical evidence.

On October 10th 2007, the FDA requested that a “boxed warning and other warnings emphasiz-ing the risk pf serious cardiopulmonary reac-tions” be added to the labeling of ultrasound micro-bubble contrast agents used in echocardi-ography, and that use of these products be con-traindicated in patients with unstable cardiopul-monary status, including patients with unstable angina, acute myocardial infarction, respiratory failure or recent worsening congestive heart fail-ure”[3]. It has been pointed out [4,5] that the FDA and other regulatory bodies have respon-sibility for product safety, but that this is not necessarily the same as patient safety. Patient safety remains the responsibility of the clinician, and so it is essential that ultrasound users keep themselves informed on safety related issues.

The behaviour of these ultrasound contrast agents (UCAs) in ultrasound fields has been comprehensively reviewed [5-8]. The scientific evidence that biological effects are induced by ultrasound exposures in the presence of UCAs is growing rapidly, although the vast major-ity of studies have involved exposure of cell cultures in vitro – model systems which may

have only limited relevance to the in vivo situa-tion.The display of a Mechanical Index (MI) on modern ultrasound scanners recognises that bubble activity (in the form of acoustic cavita-tion) may have important safety implications. This index takes the form MI = pr/√f where pr is the local rarefactional pressure in MPa, and f is frequency in MHz [9]. When no UCAs are present, the probability of bubble formation in tissue is considered to be low when MI<1. Common current contrast enhanced imaging practice is to change the MI during exposure to destroy the UCAs in the field of view in order to use the imaging of their re-appearance to demonstrate the local vasculature [1].

Biological findingsIn vitro models provide an excellent test bed for exploring the biological effects induced by ultrasound exposure of cells in the presence of microbubble contrast. However, while such studies provide useful insight into what may occur in vivo, their results must be interpreted with caution. Exposure of cells in suspension culture may result in effects different from those induced in cells growing in monolayers attached to a substrate. In suspension, both cells and microbubbles are free to move, can be in the high intensity regions of the ultrasonic field only fleetingly, and may not be in close prox-imity to each other for long. Rotation of the sample holder during exposure helps to

mitigate this effect. In monolayer cultures, bub-bles may be pushed up against the cell layer by the radiation pressure in the beam, thus maximizing the probability of interaction between the cells and contrast agents. This exposure geometry is, in turn, very different from that which might be expected during UCA use in vivo.

Most in vitro studies have concentrated on effects on red blood cells, since UCAs are pri-marily used to demonstrate vascularity. The general finding is that the pressure thresh-old to produce haemolysis is significantly reduced in the presence of UCAs [10-17]. If not destroyed by the ultrasound exposure or passage through the vasculature, UCAs may be taken up by phagocytes in the body. The effect of ultrasound on cells that have phago-cytosed such microbubbles has been studied by a number of authors, and it has been found that the threshold for cell membrane disrup-tion is reduced in the presence of contrast agents [18-20]. Similarly the threshold for endothelial cell surface changes was reduced when exposures were carried out with UCAs in contact with the cells [21,22].

In vivo studiesConclusions about the safety of the use of UCAs in the clinical setting have largely been derived from studies in small rodents. There have been no prospective randomized epidemiological studies to date, although some retrospective analysis of the use of UCAs in echocardiology have been carried out.

Since the main clinical application of con-trast enhanced ultrasound imaging so far has been in cardiology, it is natural that most published safety studies have concentrated on the heart and skeletal muscle. Here, the most common finding has been that of pre-mature ventricular contractions (PVC). First seen in human volunteers using a Mechani-cal Index (MI) of 1.5 [23], this finding has been repeated in rats. The effect was greatest when ultrasound exposure was triggered at end systole in both humans and rodents. A comparison of the induction of PVCs by the three agents namely Definity, Albunex and Optison in rodent studies found a similar threshold for all agents but exposures in the presence of Definity resulted in the lowest number of events [24-26]. A second human study was unable to induce PVCs for MI values less than or equal to 1[27].

contrast enhanced ultrasound imaging: is it safe?The use of gas-filled contrast agents raises potential safety concerns for diagnostic ultrasound imaging. While there is no proven evidence of harm resulting from clinical use of these agents, caution is advised when acquiring contrast enhanced images with mechanical indices above 0.4, since this is the threshold above which in vivo microvascular bio-effects (microvascular rupture and petechial hemorrhage) have been seen.

by dr gail ter Haar

Figure 1. Mechanical Index (MI) is frequently displayed on modern ultrasound scanners. MI is a measure of the likelihood of the formation of bubbles in tissue. (Pr is the local rarefactional pressure in MPa, f is the frequency in MHz). When no Ultrasound Contrast Agents (UCAs) are

present, the probability of bubble formation is consid-ered to be low, with MI<1.

MI = Pr √f


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Microvessel rupture was first oberved in rat spi-notrapezius muscle following ultrasound and UCA exposure from a phased array diagnostic system operating in harmonic imaging mode (2.3 MHz; MI>0.4) [28]. This rupture, and petechiae induction has been reported by other investigators in a number of biological mod-els. Clinically insignificant levels of haemolysis (<0.4%) were seen when mouse hearts were exposed through the chest wall (1.15MHz, 2.23MHz), and none could be induced in rab-bits following exposure to 5 MHz ultrasound (MI 0.5). The combination of US and UCA exposure on the microvasculature has also been studied in the intestine and kidney, with leakage and petechiae being reported in small animals, but in general not in larger animals such as the pig [29].

FDA recommendations“Reports of deaths and serious cardiopulmo-nary reactions following the administration of ultrasound micro-bubble contrast agents used in echocardiography” led to the request by FDA for a Boxed Warning for UCAs [3], and some retrospective analysis of UCA use in echocardiology. Eleven deaths were reported, four caused by cardiac arrest occurring either during infusion or within 30 minutes follow-ing the administration of the contrast agent; most of the serious but non-fatal reactions also occurred over this time frame. One patient died during a stress test, two were in severe heart failure, and the fourth, who had severe respiratory failure and pulmonary emboli, died during ventilation.

This FDA action has led to considerable discus-sion in the literature and at conferences. More than two million ultrasound examinations using microbubble contrast agents (UCAs) having been carried out since their approval by the FDA six years ago, and thus, even if all these deaths can correctly be attributed to these bubbles, the asso-ciated risk is 1:500,000. This compares favourably with the 1:1000 mortality risk associated with diagnostic coronary angiography [30], and the 1:2500 risk of myocardial infarction or death with treadmill exercise testing [31]. In a recent study in which over 18,500 cases were studied, Kuznetsky et al were unable to show an increased mortality risk associated with contrast-enhanced exami-nation, with 0.4% of hospitalised patients dying within 24 hours of echocardiography, but no sta-tistical difference in mortality between the group in which contrast agents were administered and that which received none [32].

Following a meeting of the FDA’s Cardiovas-cular and Renal Drugs advisory committee in June 2008 the position was reconsidered. Residual concern about the accumulating safety data for ultrasound contrast agents was voiced, and a requirement that products should continue to show a boxed warning highlight-ing “the risk for serious cardiopulmonary reac-tions” was placed. Definity and Optison are now contra-indicated only for patients with right-to-left, bi-directional or transient right-to-left cardiac shunts, and those with hyper-sensitivity to perflutren. The boxed warning has been modified to include the instruction “ In patients with pulmonary hypertension or unstable cardiopulmonary conditions, monitor vital sign measurements, electro-cardiography and cutaneous oxygen satura-tion during and for at least 30 minutes after DEFINITY / Optison administration” [33,34].

International statements relating to safety of ultrasound contrast agentsThere are a number of statements from profes-sional bodies representing users of medical ultra-sound. The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) has published guidelines and good clinical prac-tice recommendations for contrast enhanced ultrasound examinations [35, 36]. [Figure 2].

The American Institute of Ultrasound in Medi-cine (AIUM) has also issued a statement on the bio-effects of diagnostic ultrasound with gas body contrast agents [37], which reinforces the need for the practitioner to be aware of the safety indices (MI and TI) being used for any ultrasound examination.Although the medical significance of such microscale bioeffects is uncertain, minimizing the potential for such effects represents pru-dent use of diagnostic ultrasound. In general, for imaging with contrast agents at an MI above

0.4, practitioners should use the minimal agent dose, MI, and examination time consistent with efficacious acquisition of diagnostic informa-tion. In addition, the echocardiogram should be monitored during high-MI contrast cardiac-gated perfusion echocardiography, particularly in patients with a history of myocardial infarc-tion or unstable cardiovascular disease. Fur-thermore, physicians and sonographers should follow all guidance provided in the package inserts of these drugs, including precautions, warnings and contraindications.

ConclusionsIt should be remembered that echocardiology remains the examination of choice in patients who are sufficiently ill to warrant invasive cardi-ovascular investigation. This makes it difficult to differentiate between “association” and “cause” of any adverse events. The contrast agent safety lit-erature is thus important for assessing the hazard presented by UCAs. This literature has recently been reviewed by both the World Federation of Societies for Ultrasound in Medicine & Biology (WFUMB) [38,39] and the AIUM [14,37].

A WFUMB report has concluded that, while knowledge about the potential risk from clinical use of UCAs is incomplete, they are extremely safe, with a low incidence of side effects. There is no evidence that they are nephrotoxic or car-diotoxic, and they result in a much lower inci-dence of hypersensitivity or allergic events than current X-ray or MR contrast agents.

MI values greater than 0.4 have led to bio-effects in studies in vivo [39], with effects increasing rapidly with both increasing acoustic pressure amplitude and UCA concentration. Effects seen include premature ventricular contractions, microvascular rupture and petechial haemor-rhage. The cells that are most susceptible to damage from diagnostic ultrasound exposure to UCAs are phagocytic cells that have engulfed the microbubbles. In many cases, the damage may be reparable, and the clinical implications of such findings are not known. Good practice

20 mEdicAL imAging – Issue N°1 – Feb./Mar. 2010

Figure 2. The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guide-

lines and good clinical practice (GCP) guidelines for contrast-enhanced ultrasound examinations. The

EFSUMB position statement on safety is shown above.

Ultrasound contrast agents (UCA)

These usually take the form of stable gas filled

microbubbles, which can potentially produce

cavitation or microstreaming, the risk of which

increases with MI value. Data from small ani-

mal models suggest that microvascular dam-

age or rupture is possible. Caution should be

considered for the use of UCA in tissues where

damage to microvasculature could have serious

clinical implications, such as in the brain, the eye,

and the neonate. As in all diagnostic ultrasound

procedures, the MI and TI values should be con-

tinually checked and kept as low as possible. It

is possible to induce premature ventricular con-

tractions in contrast enhanced echocardiography

when using high MI and end–systolic triggering.

Users should take appropriate precautions in

these circumstances. The use of contrast agents

should be avoided 24 hours prior to extra-corpo-

real shock wave therapy.

Figure 3. The American Insitute of Ultrasound in Medi-cine (AIUM) statement on the bio-effects of diagnostic

ultrasound with gas body contrast agents.

Induction of premature ventricular

contractions, microvascular leakage

with petechiae, glomerular capillary

hemorrhage, and local cell killing in

mammalian tissue in vivo have been

reported and independently confirmed

for diagnostic ultrasound exposure

with a mechanical index (MI) above

about 0.4 and a gas body contrast

agent present in the circulation.

21

would, however, suggest caution when using UCAs.

References1. Cosgrove D, Harvey C. Medical and

Biological Engineering and Comput-ing 2009; 47: 8

2. Duck F. Medical Engineering & Phys-ics 2008;30:1338-1348.

3. http://www.fda.gov/CDER/drug/I n f o S h e e t s / H C P / m i c r o b u b b l e HCP.htm

4. Grayburn PA The American Journal of Cardiology 2008;101:892 – 893

5. Main ML, Goldman JH, Grayburn PA J Am Coll Cardiol 2007; 50:2434-2437

6. Sboros V. Advanced Drug Delivery Reviews 2008;60:1117-1136

7. Stride E. Cerebrovascular Disease 2009; 27 1-13

8. ter Haar G. Medical Biological Engi-neering & Computing 2009; 47 (8): 893-900

9. Apfel RE, Holland CK. Ultrasound in Med Biol 1991;17:179-185

10. Brayman AA et al. Ultrasound in Med & Biol 1996;22:927-938

11. Miller DL, Thomas RM. Ultrasound in Med & Biol 1995;21:1059-1065

12. Miller DL, Thomas RM. Ultrasound in Med & Biol 1996;22:1089-1095

13. Ivey JA et al. Ultrasound in Med & Biol 1995;21:757-767

14. Whittingham TA. Progress in Bio-physics and Molecular Biology 2007; 93:84-110

15. Miller DL, Gies RA. Ultrasound Med Biol 1998;24:285–292.

16. Miller D. Progress in Biophysics and Molecular Biology 2007; 93:314-330

17. Miller D et al. J. Ultrasound in Med 2008;27:311-632

18. Miller DL. Ultrasound Med Biol 2004;30:405–411.

19. Miller DL, Quddus J. Ultrasound Med Biol 2001; 27:1107–1113

20. Miller DL, Dou C, Song J. Ultra-sound Med Biol 2003; 29: 601-607.

21. Brayman AA, Lizotte LM, Miller MW. Ultrasound Med Biol 1999;25:1305–1320.

22. Kudo N et al. Proc IEEE Ultrason Symp 2002; 1351–1354.

23. van der Wouw P et al. J Am Soc Echocardiogr 2000; 13:288–294.

24. Li P et al. Ultrasound Med Biol 2003; 29:1341–1349.

25. Li P, Armstrong WR, Miller DL. Ultrasound Med Biol 2004; 30:83–91.

26. Dalecki D et al. Acoust Res Lett Online 2005;6:221–226.

27. Raisinghani A et al. J Am Soc Echocardiogr 2003;16:1037–1042.

28. Skyba DM et al. Circulation 1998; 98:290–293.

29. Kobayashi N et al. Circ J 2003; 67:630–636.

30. Johnson LW et al. Cathet Cardiovasc Diagn 1989;17:5-10

31. Stuart RJ, Ellestad MH. Chest 1980;77:94-97

32. Kusnetzky LL et al. J Am Coll Car-diol 2008;51:1704-1706,

33. http://www.definityimaging.com/pdf/prescribinginfo.pdf,

34. http://md.gehealthcare.com/shared/

pdfs/pi/optison_pi.pdf35. Claudon M et al. Ultraschall Med

2008; 29:28-44.36. http://www.efsumb.org/ecmus/

Clinical-Statement-202006.pdf 37. AIUM American Institute of Ultra-

sound in Medicine consensus report on potential bioeffects of diagnos-tic ultrasound. J Ultrasound Med 2008;27:503-515

38. Blomley M, Claudon M, Cosgrove D. Ultrasound in Med & Biol 2007; 33:180-186

39. Dalecki DW. Ultrasound in Med & Biol 2007; 33:205-213

The authorGail ter Haar DSc (Oxon)Head of Therapeutic UltrasoundJoint Physics Department Institute of Cancer ResearchRoyal Marsden Hospital Sutton, Surrey SM2 5PTUK


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22 mEdicAL imAging

Breast cancer is a common malignancy and one of the main causes of death among women in Western countries; the average woman has about a 12% chance of developing breast can-cer during her life. The incidence varies over the world and is highest in the USA, followed by Europe [1-3]. Women with affected first or second degree relatives are at increased risk, having a chance of 17% or higher of develop-ing breast cancer [4]. About 20% of the familial aggregation of breast cancer is a result of muta-tions of the breast cancer susceptibility genes BRCA1 and BRCA2 [5, 6]. BRCA1/2 mutation carriers have a breast cancer risk at 70 years of 57% and 49%, respectively [7].

Because of the high prevalence of breast can-cer, several Western countries offer breast can-cer screening for all women from around 40 to around 70 years of age, anually or biennially [8]. In America, the US Preventive Services Task Force recently published new recommendations on breast cancer screening, advising against rou-tine screening mammography in women aged 40 to 49 years. Instead, the USPSTF recommended biennial screening mammography for women aged 50 to 74 years and advised that the decision to be screened before age 50 should be an individual one, taking into account patients’ values regard-ing specific benefits and possible harm [9]. These recommendations have led to diverse responses indicating that the issue of screening and pre-vention is a complex one, which will require the attention and efforts of clinicians to provide the best individualized care for their patients [10].

Women with a genetic predisposition for breast cancer in their family are because of their increased risk often offered screening outside the population screening program. This mostly consists of annual mammography screening,

frequently combined with MRI and clinical breast examination, from about 25 years of age [11-13]. The breast imaging commission of the American College of Radtiation (ACR) recommends annual mammography and MRI screening for some women at high risk (greater than 20 percent lifetime risk) starting at age 30, but not before age 25 [14].

Radiation riskThe possible benefit of early detection by mam-mography screening could, however, be reduced by the risk of tumor induction through radiation. Exposure to moderate-to-high doses of radia-tion has been shown to be an established risk factor for breast cancer incidence and mortality [15, 16]. It is known that high doses of radiation evoke a higher risk of radiation-induced tumors than do low doses. In addition, the risk of radi-ation-induced breast tumors is inversely related to the age at exposure: exposure at younger ages results in a higher risk of breast cancer than exposure at older ages [15, 17, 18].

Women with a BRCA1 or BRCA2 mutation, or with a strong family history of breast cancer, are screened at younger ages, often more fre-quently, and in most cases, for a longer period of time. Although women attending mammog-raphy screening are exposed to relatively low radiation doses (3 mSv) [19], there are concerns that these low radiation doses, when received at younger age and for a longer period, could increase the risk of breast cancer [20]. Moreo-ver, these women are expected to be more sensi-tive to radiation tumor induction, because of a defect in one of the breast cancer susceptibility genes [21]. It is Therefore important to know to what extent these women could encounter adverse effects from mammography screening or other diagnostic low-dose radiation.

A systematic search of the literature was thus conducted, addressing the question of how low-dose radiation exposure affects breast cancer risk among high-risk women. The systematic search pinpointed 127 papers, of which seven were selected. The effects of low-dose radiation on breast cancer risk were presented in terms of pooled odds ratios (OR). Included studiesOf these studies, five investigated the adverse effects of exposure to low-dose radiation among mutation carriers. Two studies were conducted among women with a family history of breast cancer. The women, who were either exposed to chest x-rays or mammography screening, received a cumulative radiation dose ranging from about 0.3 to 33 mSv.

Among all high-risk women in the study, the average increased risk of breast cancer due to low-dose radiation exposure was 1.4 times greater than that of high-risk women not exposed to low-dose radiation (95% CI: 0.9- 2.1). When stratified for the total number of exposures, it was shown that exposure to a mean of ≥ 5 X-rays or mammo-grams doubled the risk compared with no radia-tion exposure (95% CI: 1.3-3.4) High-risk women exposed before age 20 were 2.5 times more likely to develop breast cancer than young high-risk women not exposed to low-dose radiation (95% CI: 1.9-3.2). When stratified by exposure, breast cancer risk was again increased between age >20 to 40; the pooled OR showed an increased risk of 1.6 (95% CI: 1.0-2.3).

ConclusionThese findings show a relation between expo-sure to low-dose radiation and an additional increase in breast cancer risk among women with a familial or genetic predisposition. Breast cancer risk is higher in high-risk women exposed before the age of 20 or in women who are frequently exposed (mean ≥5). Women exposed between 20 and 40 years of age are also at increased risk. Therefore, a careful approach is recommended when considering repeated mammography for screening young women, particularly under the age of 30. This is in line with the recommendations from the society of breast imaging and the breast imag-ing commission of the ACR in America, which recommends annual mammography and MRI

risks associated with exposure to low-dose radiation in women with genetic predisposition to breast cancerBecause of their increased risk of breast cancer and possibly an earlier age of onset, high-risk women are offered screening outside the main population screening program. However, the possible benefit of mammography screening could be reduced by the risk of radiation-induced tumors. This article assesses the adverse effects of exposure to low-dose radiation through evaluation of the published literature.

by dr marijke c. Jansen-van der Weide, marcel J.W. greuter, geertruida H. de Bock


23 – Issue N°1 – Feb./Mar. 2010

screening for BRCA1 and BRCA2 carriers and first-degree relatives of mutation carriers starting at age 30 [14]. For these cases, because mam-mography screening has a low sensitivity for detecting invasive tumors in younger women, presumably because they have denser breasts, MRI is promising, as it is unaffected by breast density, ionising radiation is not used, and sensitivity is high. However, exclusive use is limited by the high cost, limited availability, lower sensitivity for ductal carcinoma in situ (DCIS), and lower specificity of MRI [13].

Nevertheless, our results do not undermine the importance of screening among young high-risk women. It is important that, once it is known what risk high-risk women encounter with low-dose radiation such as mammog-raphy screening, attempts are made to balance this risk against the benefit of screening. In this case model studies, in which all risks and benefits are accounted for, could give a good estimate of which screening strategy is the most appropriate for high-risk women. Thus, women at increased risk of breast cancer should discuss the potential benefits and risks of screen-ing mammography with their clinicians in order to arrive at an individu-alized decision about their optimal screening strategy. They should also be informed about alternative, non-ionizing imaging modalities such as MRI.

References1. Dutch Cancer Registry, http://www.ikcnet.nl, 2006.2. Jemal A et al. Cancer statistics, 2005. CA Cancer J Clin 2005; 55: 10-30.3. Loman N et al. Family history of breast and ovarian cancers and BRCA1 and

BRCA2 mutations in a population-based series of early-onset breast cancer. J Nat Cancer Inst 2001; 93: 1215-1223.

4. Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women with-out the disease. Lancet 2001; 358:1389-1399.

5. Nathanson KN, Wooster R, Weber BL. Breast cancer genetics: What we know and what we need. Nature Medicine 2001; 7:552-556.

6. Verhoog LC et al. Large regional differences in the frequency of distinct BRCA1/BRCA2 mutations in 517 Dutch breast and/or ovarian cancer families. Eur J Cancer 2001; 37: 2082-2090.

7. Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 2007; 25: 1329-1333.

8. Shapiro S et al. Breast cancer screening programmes in 22 countries: current policies, administration and guidelines. International Breast Cancer Screening Network (IBSN) and the European Network of Pilot Projects for Breast Cancer Screening. Int J Epidemiol 1998; 27: 735-742.

9. U.S. Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Task Force Recommendation Statement. Ann Intern Med 2009; 151: 716-726.

10. Murphy AM. Mammography screening for breast cancer. A view from 2 worlds. JAMA 2010; 303: 166-167.

11. Kriege M et al. Efficacy of MRI and mammography for breast-cancer screen-ing in women with a familial or genetic predisposition. N Engl J Med 2004; 351(5): 427-437.

12. Leach MO et al. The MARIBS study group. Screening with magnetic reso-nance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet. 2005; 365(9473): 1769-1778.

13. Warner E et al. Systematic review: using magnetic resonance imaging to screen women at high risk for breast cancer. Ann Intern Med 148 (9): 671-679.

14. Lee CH et al. Breast cancer screening with imaging: recommendations from the society of breast imaging and the ACR on the use of mammography, breast MRI, breast ultrasound, and other technologies for the detection of clinically occult breast cancer. J Am Coll Radiol 2010; 7: 18-27

15. Preston DL et al. Radiation effects on breast cancer risk: a pooled analysis of eight cohorts, Radiat Res 2002; 158: 220-235.

16. Ronckers CM, Erdmann CA, Land CE. Radiation and breast cancer: a review of current evidence. Breast Cancer Res 2005; 7: 21-32.

17. BEIR 7. National Research Council, Committee on the Biological Effects of Ionizing Radiation. Health effects of exposure to low levels of ionizing radia-tion (BEIR VII Phase 2). National Academy Press, Washington DC, 2006.

18. Thompson DE et al. Cancer incidence in atomic bomb survivors. Part II: Solid tumours, 1958-1987. Radiat Res 1994; 137: S17-67.

19. Van der Helm OM et al. Results of Technical Quality Control in the Dutch Screening Programma (2003-2004), National Expert and Training Centre for Breast Cancer Screening, The Netherlands, (2006).

20. Wakeford R. The cancer epidemiology of radiation. Oncogene 2004; 23: 6404-6438.

21. Broeks A et al. Identification of women with an increased risk of developing radiation-induced breast cancer: a case only study. Breast Cancer Res 2007; 9: 106-114.

The authorsMarijke C. Jansen-van der Weide PhD, Epidemiologist& Marcel. JW Greuter, Geertuida H De Bock Department of RadiologyUniversity Medical Center Groningen, Groningen, The Netherlands Tel +31 50 3614467; e-mail [email protected]

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24 mEdicAL imAging

Focused research efforts over the last decade have helped establish breast magnetic reso-nance imaging (MRI) as an important tool for the detection and characterization of breast can-cer. The value of breast MR imaging is derived primarily from the high sensitivity of contrast material enhancement in the detection of breast cancer [1]. However, though sensitivity is con-sistently high across different clinical studies, specificity still remains a challenge [2, 3]. The current consensus is that MR is an excellent tool for determining tumor extent, and should espe-cially be performed in dense breasts. However, due to low specificity, it becomes necessary to perform biopsy of additional lesions detected on MR. The results of multiple studies show that preoperative MR is recommended in patients with breast cancer who are scheduled for breast-conserving surgery. Breast MRI offers a multi-contrast approach which, combined with mor-phological features, may provide the optimal approach to diagnosis and management [4]. A brief overview of current breast MRI tech-niques is presented below including dynamic contrast enhanced MRI, diffusion MRI, spec-troscopy, perfusion MRI, MR elastography, concluding with a computer aided assessment of breast lesions.

Dynamic Contrast Enhanced MR Imaging (DCE-MRI)This is the most routinely used MR imaging technique for the assessment of breast lesions. It has shown the most promise for discrimi-nating between malignant and benign tumors; however even with this technique, specificity is in the range of 37%-97% [5]. In DCE-MRI, a dynamic imaging is performed after injec-tion of a contrast agent and the signal inten-sity on a T1 weighted dynamic sequence has specific contrast uptake patterns for malignant and benign, with malignant lesions showing a higher ‘signal enhancement ratio’, larger values of ‘maximum slope’, and shorter ‘time to peak of enhancement’ [Figure 1]. Multivariate models combining morphology and contrast uptake dynamics have the highest predictive val-ues and exceed that based on lesion architec-tures or intensity patterns alone [4]. However, the conflicting requirements of high spatial

resolution and high temporal resolution have precluded the routine use of both fea-ture types in clinical studies; recent studies explore optimum temporal resolution [6] and pulse sequences for combined high spatial and temporal resolution [7].

The applications of DCE-MRI extend beyond diagnosis to therapeutic monitoring and for breast screening. The non-invasive nature of MRI makes it an ideal candidate for moni-toring and increases the potential for detec-tion of early response [8] and for treatment optimization [9]. The American Cancer Society (ACS) has established guidelines for screening with breast MRI as an adjunct to mammography [10]. For breast MRI, the

guidelines indicate that screening can poten-tially identify cancer in patients of specific risk groups, e.g. high-risk patients facing a lifetime risk of ~20–25%.

Diffusion Imaging Diffusion weighted MR imaging (DW-MRI) provides unique information about the state of the molecular translational motion of water. This allows inference about local tissue architecture which is a sensitive early indica-tor of abnormality and cellularity. The mean or average diffusivity in tissue is quantified by an index called the Apparent Diffusion Coefficient (ADC). It is anticipated that DW-MRI will detect early changes in morphol-ogy and physiology of tissues associated with changes in water content such as changes in the permeability of cell membranes, cell swelling and/or cell lysis.

detection and diagnosis of breast cancer with novel magnetic resonance imaging techniquesby Prof. Usha sinha & Prof. shantanu sinha

Figure 1. Contrast-enhanced (CE-) MRI of the left breast shows an enhancing lesion that is analyzed by a manually drawn ROI (L1).The upper row shows from left to right: T1-weighted post-contrast image, post-contrast subtraction image and signal intensity–time curve of the chosen ROI, which shows wash-out kinetics. The lesionwas assessed to be highly suggestive of malignancy (breast MRI score 7; BI-RADS 5). MRE images of reconstructed viscoelastic properties are shown in the lower row (left T2-weighted anatomical image = magnitude image, middle elasticity

map, right viscosity map). A corresponding ROI of the target lesion was chosen. The lesion showed high values on the elasticity and viscosity maps, which corresponds with very stiff tissue. Histopathology proved this lesion to be an

invasive ductal carcinoma of 20 mm in size.Image reprinted courtesy of Springer, publishers of Eur. Radiol. from Siegmann KC et al. Diagnostic value of MR

elastography in addition to contrast-enhanced MR imaging of the breast-initial clinical results. Eur Radiol 2010 ; 20: 318-325.


25 – Issue N°1 – Feb./Mar. 2010

Early studies using DW-MRI to characterize breast lesions found that the ADC values of malignant breast tumors were significantly reduced compared to benign and normal fibro-glandular tissue, presumably from increased cel-lularity in malignancy [11]. DW-MRI evaluation of 60 women showed a spe-cificity of 81% and sensitivity of 80% to discriminate malignant from benign lesions [12]. Guo et al [13] showed that tumor cellularity correlated inversely with tumor ADC and that malignant breast tumors had a higher cellularity and a lower ADC than benign breast tumors. A recent study confirmed that DWI shows potential for improving the positive predictive value of breast MRI for lesions of varied types and sizes [14]. Diffusion MRI has also been shown to detect early response to neoadjuvant therapy prior to tumor size changes [8, 15] including voxel by voxel ADC changes [Figure 2] [16] and more recently, to identify patients most likely to respond to treatment [17].

SpectroscopyMR spectroscopy (MRS) is a biochemical marker that allows the non-inva-sive detection of proton metabolites. Cancerous lesions demonstrate elevated composite choline levels arising from increased cellular proliferation. Sev-eral groups have demonstrated that MRS either alone or in conjunction with MRI improves specificity of breast MR [18]. A multi-institutional study by Kratz-Bull et al. confirmed the robustness of total choline-containing (tCho) compounds from MRS and the improvements in specificity in characteriz-ing breast lesions [19]. The consensus is that MRS is useful in larger tumors (>1 cm); however it may be limited in its ability to discriminate benign breast lesions from phyllodes tumors of benign and borderline malignancy [20]. MR spectroscopic imaging has recently produced the highest spectro-scopic resolution (0.25 cm3) and offers the potential for mapping choline distributions across the lesion [21].

Perfusion MR imaging of the breastPerfusion imaging provides information on microvascular distribution and density and is performed by tracking the changes in the apparent

relaxation rate T2* during the first passage of a contrast bolus. T2* refers to the measured loss of transverse magnetization in a gradient-echo sequence that is due to the combined effects of the inherent spin-spin relaxation time T2 and macroscopic magnetic field homogeneities (static field and paramagnetic contrast agent). The main limitation of including perfusion imaging in a MR breast protocol is the need for two contrast boluses: one for the first pass bolus tracking to monitor susceptibility induced losses and the other to monitor the contrast uptake. An early study evaluated perfusion imaging versus DCE-MR [22] and found a strong intensity loss in malignant breast tumors. This is in marked con-trast to fibroadenomas that showed little or no perfusion effects, whereas in DCE-MRI the enhancement patterns of malignant lesions and fibroadenomas overlapped. Recent studies on larger population cohorts concluded that perfusion imaging increases the level of specificity, even up to 100% in one study [23, 24].

Magnetic Resonance Elastography (MRE):MRE is an elegant, relatively new approach and measures the elastic properties of tissue. It is a phase-contrast-based MRI imaging technique that can directly visualize and quantitatively measure propagating acous-tic strain waves in tissue-like materials subjected to harmonic mechani-cal excitation. Quantitative values of elasticity, e.g. shear modulus can be calculated from the acquired data [Figure 1]. There have only been a few preliminary studies using this technique; initial studies have indeed confirmed that MRE could be a non-invasive ‘palpation’ in that breast tumors revealed higher shear elasticity than normal breast tissue [25]. Xydeas et al. have applied MRE to discriminate between malignant and benign tumors [26]. The increased diagnostic accuracy of a combined MRE and DCE-MR in a recent study confirms the potential of MRE [27]. MRE technology is not, as yet, mature for clinical use but the initial results are quite promising.

Computer aided analysis for Breast MRIAutomated breast lesion segmentation methods have been explored by several groups and are the first step in computer aided analysis. Proposed segmentation methods include fuzzy c-means clustering [28], neural network classifiers [29], and multi-parametric techniques [30]. Fuzzy c-means clustering refined by level sets has been proposed recently for segmenting lesions from dynamic scans and shows potential for accu-rate tracking of lesion volume changes in treatment [31]. Lesion fea-tures have been extracted from both 2D as well as from the entire 3D segmentation. Several measures of lesion shape and lesion border

Figure 2. Functional diffusion maps (fDM) for responsive and non-responsive breast treatment. Top and bottom rows show respectively from left to right the treatment effect (corresponding voxel ADC in pre-treatment vs post treatment maps), and fDM treat-

ment overlay on one anatomical slice. fDM is a subtraction map of the post-treatment ADC map from the pre-treatment ADC map. Red in the fDM maps correspond to

voxels with an increase in ADC, green to voxels with no change in ADC, and blue to voxels with a decrease in ADC. The patient whose data are shown on the top frames was found to be a positive responder while the patient whose data are shown below

was a negative responder to treatment.Image reprinted courtesy of Springer, publishers of Inf Process Med Imaging from Ma B et al,. Voxel-by-voxel functional diffusion mapping for early evaluation of

breast cancer treatment. Inf Process Med Imaging. 2009;21:276-87.

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characteristics have been evaluated as potential indices of the lesion structure [32)]. A recent study indicates that texture analysis of breast MRI can differ-entiate cancer from normal tissue with the potential to distinguish between lobular and ductal cancer, thus providing accurate computer-assisted characterization of breast lesions [33].

Several studies have shown that computer-assisted breast MR can be useful either alone or in conjuction with a radiologist [34]. A few groups have also worked on automated segmentation, rating and classification of breast tumors [35], combining automatically extracted morphological and dynamic features, and visualization of the data [36]. A promising new report is on extending computer-aided diagnosis of breast DCE MR lesions from discriminating to prognostic tasks [37]. ConclusionsBreast MRI is an area of active research and offers significant poten-tial for lesion characterization: contrast uptake with DCE-MRI, mor-phology with high resolution structural imaging, cellularity with dif-fusion imaging, vascular networks through perfusion MR imaging, and biochemical composition with MR spectroscopy. This battery of techniques allows a multi-pronged approach that can be directed

toward diagnosis and therapy monitoring. Challenges still remain and further improvement in acquisition methods will be required to enable a comprehensive multi-parametric examination of the bilateral breast in clinically relevant times [38]. Inclusion of the indices extracted from the multi-parametric imaging in a robust classifier framework will ultimately help achieve a higher specificity for breast MR imaging; establishing it as a one-stop examination for the screening, diagnosis, prognosis, longitudinal monitoring and management of patients with breast lesions.

ReferencesReaders are referred to Sinha et al for a more detailed review of the information presented in the above article[3].

1. Rotaru N & Luciani A. J BUON 2004; 9: 77-82. 2. Morris EA. Magn Reson Imaging Clin N Am 2010; 18: 57-74.3. Sinha S, Sinha U. Recent advances in breast MRI and MRS. NMR Biomed 2009;

22: 3-16. 4. Schnall MD et al. Radiology 2006; 238: 42-53.5. Buadu LD et al. Radiology 1996; 200: 639–649.6. El Khouli RH et al. J Magn Reson Imaging 2009; 30: 999-1004.7. Medved M et al. Magn Reson Imaging 2010; 28:16-21. 8. Pickles MD et al. Breast Cancer Res Treat 2005; 91: 1-10. 9. Martincich L et al. Breast Cancer Res Treat 2004; 83: 67-76. 10. Saslow D et al. Cancer J Clin 2007; 57: 75–89.11. Sinha S et al. J Magn Reson Imaging 2002; 15: 693–704.12. Marini C et al. Eur Radiol. 2007; (Epub ahead of print). 13. Guo Y et al. J Magn Reson Imaging 2002; 16: 172-178. 14. Partridge SC et al. Am J Roentgenol. 2009; 193:1716-1722.15. Theilmann RJ et al. Neoplasia 2004; 6: 831-837. 16. Ma B et al. Inf Process Med Imaging 2009; 21:276-287.17. Iacconi C et al. Eur Radiol 2010; 20:303-308. 18. Meisamy S et al. Radiology 2005; 236: 465-475. 19. Katz-Brull R et al. J Natl Cancer Inst 2002; 94: 1197-1203. 20. Tse GM et al. Am J Roentgenol 2003; 181: 1267-1272. 21. Hu J et al. Med Phys 2009; 36: 4870-4877.22. Kuhl CK et al. Radiology 1997; 202: 87–95.23. Kvistad KA et al. Radiology 2000; 216: 545–553.24. Huang W, et al. Radiology 2004; 232: 585–591.25. Lorenzen J et al. Rofo 2002; 174: 830-834.26. Xydeas T et al. Invest Radiol 2005; 40: 412-420.27. Siegmann KC et al. Eur Radiol 2010 ; 20: 318-325. 28. Chen Wet al. Acad Radiol 2006; 13: 63–72. 29. Woods BJ et al. J Magn Reson Imaging. 2007; 25: 495-501.30. Jacobs MA et al. Radiology 2003; 229: 225–232.31. Shi J et al. Med Phys 2009; 36: 5052-5063.32. Liney GP et al. J Magn Reson Imaging 2006; 23: 493–498.33. Holli K et al. Acad Radiol 2010; 17:135-141. 34. Chen W et al. Med Phys 2004; 31: 1076–1082.35. Gilhuijs KG et al. Radiology 2002; 225: 907–916.36. Subramanian KR et al. Comput Med Imaging Graph 2004; 28: 435–444.37. Bhooshan N et al. Radiology 2010 Feb 1. [Epub ahead of print]38. Han M et al. Magn Reson Med 2009; 62:1221-1231.

26 mEdicAL imAging – Issue N°1 – Feb./Mar. 2010

The technical exhibition offers industry and commerce the opportunity to exhibit to the leaders and decision-makers in the UK field whilst contributing to the close partnership between manufacturers and service providers.

w

7-9 june 2010Birmingham, uK

wHO ATTENDS?Radiologists

Business Managers

Physicists

Radiology Service Managers

Radiographers

Oncologists

IT Managers

Academics

Hospital Managers

SonographersEngineers

Technicians

Radiotherapists

RadiochemistsPurchasing & Supplies Managers

Physicians

nurses

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The exhibition with the status of a learning environment in its own

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For further information about booking exhibition space, visiting the exhibition or registering for the conference please visit

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The authors:Usha Sinha, Ph.D. Professor and Chairperson, Department of Physics, San Diego State University, 5500 Campanile Dr. San Diego, CA-92182-1233. Ph.No. (619)-594-1791 Cell: (310)-460-8897 E-mail: [email protected]

Author for Correspondence:Shantanu Sinha, Ph.D.Professor, Department of Radiology, UCSD School of Medicine, 3510 Dunhill Street San Diego, CA-92121-0852. Ph.No. (858)-534-2004 Cell: (310)-435-3994 E-mail: [email protected]

27

New stent improves ability to keep vessels open in dialysis patients

Kidney dialysis patients often need repeated procedures, such as balloon angioplasty, to open blood vessels that become blocked or narrowed at the point where dialysis machines connect to the body. These blockages can impact the effec-tiveness of hemodialysis. A new FDA-approved stent graft can keep these access points open longer, reducing the number of procedures that dialysis patients may need, according to research from the University of Maryland pub-lished in the February 11, 2010, edition of the New England Journal of Medicine.The prospective multi-center study took place at 13 sites across the country and enrolled nearly 200 patients. Ninety-seven patients received angioplasty with the new stent, which is a small metal scaffold inserted in the patient’s arm, and 93 received angioplasty alone. The researchers found that patients with the stent graft were more than twice as likely to have open vessels compared to the angioplasty only group after six months. The recurrence of res-tenosis was nearly three times lower with the stent group, (27.6 percent vs. 77.6 percent). In later follow-up, some patients still had functioning grafts two years after the stent graft was first implanted.http://content.nejm.org

Clustering MRSA in Europe indicates diffusion through regional health-care networks

A study has found that methicillin-resistant Sta-phylococcus aureus (MRSA) occurs in distinct geographical clusters across Europe, indicating that MRSA is being diffused by patients moving between hospitals rather than spreading freely in the community. The study, published recently in PLoS Medicine, used an interactive web

tool to map different strains of S. aureus across the continent.MRSA infections have become more prevalent in hospitals over the past ten years, and infor-mation about its geographical distribution could help understand how it spreads and how to control it. In 2006 Hajo Grundmann, of the University Medical Centre in Groningen in the Netherlands, and colleagues assembled a large group of collaborators in 450 European hos-pitals located in 26 different countries. These hospitals collected both MRSA and methicillin-sensitive S. aureus (MSSA) isolates from infected patients. MRSA emerges when MSSA clones acquire resistance to antibiotics. National labo-ratories identified specific strains of S. aureus by molecular typing and entered this information into a Web-based mapping application which is publicly available (http://www.spatialepidemiol-ogy.net/srl-maps).The results show that strains of MRSA tend to cluster within regional borders and, in several instances, were associated with individual hos-pitals. This suggests that MRSA is mainly spread by patients who are repeatedly admitted to dif-ferent hospitals. The researchers coclude that control efforts aimed at interrupting the spread within and between health care institutions may not only be feasible but ultimately successful. http://www.plosmedicine.org/

Defeatism is undermining evidence that chronic fatigue syndrome can be treatedAn air of defeatism exists within the medical profession about chronic fatigue syndrome and is undermining evidence that the condition can be treated, argue three senior doctors in a recent issue of the British Medical Journal. Dr Alastair Santhouse, consultant at The South London and Maudsley NHS Foundation Trust and colleagues from Institute of Psychiatry, King’s College Lon-don, argue that the media has largely portrayed the condition as a progressive, paralysing and commonly fatal illness, with little being said about the uncertainties and controversies that this diagnosis has always attracted. The authors point out that severe presentations of chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) are unusual, and that, if a diagnosis of CFS/ME is made, data clearly show that mortality is not significantly increased. The greatest risk to life is likely to be suicide, but this is often linked to depression that can be effectively treated.Treatments such as cognitive behavioural therapy and graded exercise therapy have also been shown to work in CFS/ME and are recommended by the UK National Institute for Health and Clini-cal Excellence (NICE). In patients with severe CFS/ME, such programmes may be prolonged, but they can be the trigger for improvements and sometimes dramatic recovery.The alternative is often no treatment, and this can have a disastrous effect on patients, who may feel

that the medical profession has given up on them as hopeless cases. Undoubtedly current treat-ments could be improved, recovery may not be complete in many cases, and access to services for those too disabled to attend hospital clinics needs to be improved. Furthermore, doctors are often uncertain about what they are dealing with, and perhaps inevitably a breakdown of trust between doctors and the patients and their families often occurs. The medical profession must continue to go with the evidence in choosing treatments for what can be a fraught clinical situation. http://www.bma.org.uk/

Short-term radiation therapy successful in treating breast cancer

An intense three-week course of radiation therapy is just as effective as the standard five-week regimen for women with early-stage breast cancer. Dr. Tim Whelan, a professor of oncology of the Michael G. DeGroote School of Medicine at McMaster University, Canada, led a team of researchers who found that women who received the accelerated therapy have a low risk of recurring breast cancer for as long as 12 years after treatment. The results were published in a recent issue of the New England Journal of Medicine (NEJM). Between April 1993 and September 1996, researchers randomly assigned 1,234 women from Ontario and Quebec, Canada, to be treated with either accelerated radiation or standard radiation. The participants were fol-lowed for 12 years to determine if the acceler-ated whole-breast radiation was as effective as the standard treatment. A decade after treat-ment, breast cancer returned in 6.2 percent of patients treated with the accelerated radiation therapy, compared to 6.7 percent for patients treated with standard therapy. The study concluded that a shorter, more intense course of therapy is as safe and effec-tive as the standard treatment for select women who have undergone breast-conserving sur-gery. Women who receive a three-week treat-ment, namely accelerated hypofractionated whole-breast irradiation, have a low risk of side effects and recurrence of the cancer more than decade after treatment. It is just as effective as the standard five-week course of radiation following surgery to remove the tumor. http://dailynews.mcmaster.ca

nEWs in BriEF – Issue N°1 – Feb./Mar. 2010

28 HosPiTAL HygiEnE

Methicillin-resistant Staphylococcus aureus healthcare–associated infections (MRSA HAIs) are one of the most common types of infection which patients in the healthcare setting are at risk of acquiring. In a recently published study the most severe form of MRSA, invasive MRSA, was documented to have affected 94,000 patients in the United States in 2005. Of these, 86% were healthcare-associated and approximately 20% of all patients infected with invasive MRSA died [1]. Other organisms such as Clostridium difficile and vancomycin-resistant Enterococci are also responsible for causing infections in the health-care setting. The connection between infectious organisms colonizing one patient and the subse-quent colonization in another patient had been well understood even before the Hungarian obstetrirican Ignaz Semmelweis castigated his colleagues for their poor hand hygiene prac-tices more than one hundred and fifty years ago. Hand hygiene has been a major tenet of infec-tion control practice for many years. Even in 1846 it had been recognized by Semmelweis as highly effective in reducing morbidity and mor-tality in patients [2]. It was recognized then, and more clearly understood now, that cross trans-mission of pathogenic organisms takes place through a sequential process from one patient via the healthcare worker to the next patient. In this process inadequate hand hygiene agents or protocols result in the continued contamina-tion of the healthcare workers’ hands and thus ongoing transmission. It has been clearly shown

that good hand hygiene agents and practices can interrupt transmission and are associated with a decrease in infections [3].

Our organization, Novant Health, realized that it was necessary to develop a comprehensive hand hygiene program to address HAIs in our facilities. The program needed to address the healthcare workers’ role in the transmission of

HAIs, the processes of transmission, the inter-ventions needed to prevent transmission and the outcomes which our patients experienced. Equally importantly, we needed a collective leadership voice to speak out as loudly as Sem-melweis against poor hand hygiene practices and in support of the program developed to protect our patients against HAIs.

The president of our organization took the lead in pushing the development of our program. He had a passion and unrelenting drive to do this follow-ing the death of an infant from a MRSA infection in one of our facilities. He felt that he was just as responsible, if not more so, for the quality of care and safety of our patients, as he was for the opera-tions and financial stability of our organization. He received Board of Trustees approval to make this a priority for our organization in 2003.

The major elements or our program were based on the Centers for Disease Control and Preven-tion (CDC) recommendations for Hand Hygiene practices. We also follow all CDC guidelines on isolation practices for patients with resistant or pathogenic infections using the recommenda-tions on transmission-based precautions [4]. We educated all employees concerning their role in transmitting infections to our patients and what they could do to prevent such transmission. We evaluated the technologies available and chose an alcohol-based hand sanitizer. We worked with all clinical units to determine the number and place-ment of the hand sanitizer dispensers in order to ensure ready access for the staff. At the time, none of the newer wireless or radio frequency moni-toring technologies were readily available for use. Therefore, we chose to use clinically experienced hand hygiene monitors to observe hand hygiene behavior throughout the acute care facilities, and to give immediate feedback to the noncompliant staff and their managers. The monitors also col-lected and reported the compliance data to the organization’s leadership. We had known that our healthcare associated MRSA infection rates were above the national benchmark rate and thus were able to set a lower outcome target MRSA infec-tion rate for our organization. Lastly, we chose an aggressive, hard hitting, internal communica-tions plan to push and challenge our staff towards best practices, full compliance and an in depth appreciation of the healthcare workers’ role in their patients’ infections.

Hand hygiene: the key to reducing methicillin-resistant Staphylococcus aureus HAis methicillin-resistant staphylococcus aureus (mrsA) infections are the most common healthcare–associated infections (HAi) seen within the acute care setting. The major mode of transmission from patient to patient is through the bedside care providers via contaminated hands. Published studies have associated improvements in hand hygiene compliance with decreases in HAi. This article describes a program that was implemented in a large healthcare organisation in the southeastern United states comprising 10 integrated healthcare facilities, to address unsatisfactory hand hygiene compliance rates. The key elements of the program were the use of alcohol-based hand sanitizer and the dedication of resources to collect and report compliance data. in addition, mrsA HAi rates were followed for all the acute care facilities. it was found that the improvements in hand hygiene compliance translated into a real and significant decrease in the number of hospital-acquired mrsA infections.

by dr James W. Lederer

Figure 1. An example of the hard-hitting posters used in the succesful campaign to encourage Novant

health care personnel to adopt best practices. The posters are available free-of-charge to all health care

organisations which request them. (www.washinghandssaveslives.org)


29


www.ihe-online.com/comment/MRSA


The marketing and communications depart-ment’s role was critical. The ability to come up with strong messaging significantly accelerated our overall performance. Some examples of the campaigns included the following:• Traditional nursing and physician memos and

posterboard communications• Hard-hitting posters (for example, “What You

Can’t See Is Killing Them,” “You Could Kill Him with Your Bare Hands”) on the likelihood of staff harming patients because of poor com-pliance [Figure 1].

• Hand hygiene fairs, where staff could view post-ers on hand hygiene and infection prevention

• An internal marketing campaign, with life-sized cartoon cut-outs emphasizing hand hygiene at visitor entrances and lobbies.

As stated, the posters used in the internal com-munication campaigns were often “hard hitting,” which frequently provoked controversy. The intent was both to challenge the employees and to inform them of the importance of hand hygiene in the care of patients and the significant negative out-comes resulting from noncompliance. The mar-keting challenge was to help create a culture where noncompliance was unacceptable and where patient safety became a responsibility of individual employees. All posters, stickers, ads, banners and other marketing initiatives were posted on to our website (www.washinghandssaveslives.org) and have been made available at no cost to any health care organization requesting them. To date, more than 900 organizations, including 41 from outside the United States, have accessed the materials.The hand hygiene monitors have been able to conduct 2,000-2,500 individual compliance observations a month across all participating facilities. The hand hygiene compliance data

show a marked and sustained improvement in all regions and in our system as a whole from 2006 to the present. The organization has been above 90% compliance since November, 2006. The MRSA HAI rate decreased from 0.52 to 0.16 MRSA HAIs per 1,000 patient days, representing a 69% reduc-tion associated with improved compliance from 2006 to July, 2009 [Figure 2]. At the patient level, this translated into 105 fewer MRSA HAIs for the entire system—from 234 patients in 2005 to 129 patients in 2008.

Such a simple process has such an important outcome. How can other healthcare organiza-tions achieve similar results? Recognition of the problem and a leadership focus on outcomes is paramount. The problem and solution lies with each individual in the organization. In order to drive high compliance, employees must under-stand the unintended consequences of their poor performance and receive real-time feedback on their individual non-compliance and the organi-zation’s performance as a whole. The unique role the internal communications department played in elevating staff knowledge and awareness helped with employee appreciation of poor hand hygiene compliance as a significant patient safety issue. Reporting actual patient outcomes and organizational MRSA HAI rates helps to impress

on staff the link between their behavior and what their patients experience. Through repeated cycles of observation, feedback and reporting and observation, the expectation is that the desired behavior will become more automatic and less dependant on observational pressure. The key challenge is to completely embed hand hygiene as an automatic and unconscious competency in the healthcare culture for all caregivers, much like the campaign to make the fastening of seatbelts an automatic response when driving or riding in a car. The same level of embedded behavior is needed, not only with hand sanitization, but also with all other infection prevention practices, such as isolation precaution barrier compliance.

References1. Klevens RM, Morrison MA, Nadle J et al. Active Bac-

terial Core Surveillance MRSA Investigators. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 2007;(15):1763-1771.

2. The first (slightly abridged) translation into English of Semmelweis’ treatise, was published in 1941 by F.P. Murphy in ‘Medical Classics’ 5 (1941), 339-478, 481-589, 591-715, 719-773.

3. Pittet, D, Allengranzi B, Sax H et al. Evidence-based model for hand transmission during patient care and the role of improved practices. http://infection.the-lancet.com. 2006; Vol 6: 641-652.

4. Boyce JM, Pittet D. Healthcare Infection Control Practices Advisory Committee; HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force: Guideline for Hand Hygiene in Health-Care Settings. Recommen-dations of the Healthcare Infection Control Prac-tices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Society for Healthcare Epidemiology of America/Association for Professionals in Infection Control/Infectious Diseases Society of America. MMWR Recomm Rep 51(RR-16):1-45, Oct. 25, 2002.

The authorJames W. Lederer, Jr., M.D., Medical Director, Clinical Improvement, Novant Health, Winston Salem, North Carolina, USAe-mail: [email protected]

Figure 1. The HAI methicillin-resistant Staphylococcus aureus (MRSA) infection rates for the two largest regions of the system in North Carolina, SPR = Southern Piedmont, TR = Triad and NH = Novant Health System.

Any new facilities or regions added were included in the data collection but aggregated into one of the two regions. The data show a decrease in MRSA HAI infections for the system from 0.52 to 0.16 infections per

1,000 patient days, representing a reduction of 69%.

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Novant Heath is a large, not-for-profit healthcare system in the southeastern United States. The service area for the system, which is composed of 10 integrated hospital facilities, encompasses North Carolina, South Carolina and Virginia. The facilities range in size from 22 beds to more than 950 beds, with a total of 2,850 beds within the 10 acute care hospital facilities. The system also

includes more than 1,400 employed physicians and physician extenders distributed across the service area in 246 practices, as well as 92 imaging centers spread predominately throughout the southeastern United States. The system cares for more than 100,000 inpatient discharges per year and entails more than 3.2 million outpatient visits to the physician practices.

30 sciEnTiFic LiTErATUrE rEviEW

Diabetes and cardiovascular disease prevention in older adults.Cigolle CT et al. Clin Geriatr Med 2009; 25(4): 607-41.Cardiovascular disease is the major cause of death as well as a leading cause of disability and impaired quality of life in older adults with diabe-tes. Therefore, preventing cardiovascular events in this population is an important goal of care. Avail-able evidence supports the use of lipid-lowering agents and treatment of hypertension as effective measures to reduce cardiovascular risk in older adults with diabetes. Glucose control, smoking cessation, weight control, regular physical activ-ity and a prudent diet are also recommended, although data supporting the efficacy of these interventions are limited. While reducing cardio-vascular morbidity and mortality remains a pri-mary objective of preventive cardiology in older adults with diabetes, the impact of these inter-ventions on functional well-being, cognition, and other geriatric syndromes requires further study.

Secondary prevention of stroke.MacDougall NJ et al. Expert Rev Cardiovasc Ther 2009;7(9):1103-15.Stroke and transient ischaemic attacks result from a range of mechanisms. Secondary preven-tion includes both conventional approaches to vascular risk-factor management (blood pres-sure lowering, cholesterol reduction with stat-ins, smoking cessation and antiplatelet therapy) and more specific interventions, such as carotid endarterectomy or anticoagulation for atrial fibrillation. The relative importance of even con-ventional risk factors in stroke differs from coro-nary artery disease. Large clinical trials produce information on most aspects of stroke preven-tion. Stroke and transient ischaemic attacks are now recognised as medical emergencies, with a high early risk of recurrence, and evidence is accumulating to support the importance of immediate institution of secondary preventative

treatments. This article reviews current literature on the secondary prevention of stroke.

A practical approach to the prevention of miscarriage: progesterone therapy.Check JH. Clin Exp Obstet Gynecol. 2009;36(4):203-8.Vaginal progesterone therapy was evaluated in women with a previous history of miscarriage or in women with infertility related to luteal phase defects. The results indicate that using progester-one to diminish the risk of miscarriage is benefi-cial. Other methods of stimulating progesterone production, e.g., human chorionic injections, are also effective. Progesterone therapy, espe-cially when given vaginally, has few side-effects and is safe. Thus the evidence suggests that one should err on the side of over-treatment rather than under-treatment in certain circumstances, e.g., advanced woman’s age, previous history of miscarriage, or the use of follicle maturing drugs.

The role of modifiable pre-pregnancy risk factors in preventing adverse fetal outcomes among women with type 1 and type 2 diabetes.Inkster ME et al. Acta Obstet Gynecol Scand. 2009; 88(10):1153-7.The authors of this paper investigated the foetal outcomes of pregnancy in women with pre-exist-ing diabetes in relation to pre-pregnancy risk fac-tors using a community-based cohort of women in Tayside, Scotland. There were 211 pregnancies in 132 women with insulin-requiring type 1 and 2 dia-betes between January 1993 and December 2005. Adverse fetal outcome was classified as spontane-ous miscarriage, termination for medical reasons, stillbirth, neonatal death or congenital malforma-tion, and occurred in 61 (29%) pregnancies. Moth-ers with poor glycaemic control pre-conceptually and at booking had almost a three-fold increase in adverse fetal outcome compared with mothers hav-ing fair control. Mothers who were still smoking at the booking visit had a two-fold increase in adverse foetal outcome. Further improvement in the man-agement of diabetes and pregnancy is needed through enhanced preconception services address-ing the full spectrum of modifiable risk factors.

Long-term cervical cancer prevention strategies across the globe.Cuzick J. Gynecol Oncol. 2010 Feb 1. Worldwide, there are several approaches for the prevention of cervical cancer, and in the near future it is likely that human papillomavirus (HPV) vaccination and HPV-based screening will be

complementary strategies. In the US, professional guidelines on HPV screening recommend a co-testing approach utilising HPV DNA testing and cytology in women aged >/=30 years. However, a growing body of evidence indicates that HPV test-ing is more sensitive than cytology, suggesting that HPV DNA testing may be more useful as the sole primary screening modality, especially for newly implemented programmes. HPV vaccination pro-grammes targeted at young girls have been widely implemented in several developed countries, and currently available data confirm the long-term effi-cacy of the VLP-based vaccines against HPV-related disease over periods of up to eight years. If these HPV vaccines continue to demonstrate sustained and durable efficacy, less frequent screening may become a reality, but screening will continue to play an important role in providing protection for dis-ease caused by types not included in these vaccines. However, a significant HPV vaccination-induced reduction in cervical cancer burden is not likely to be realised for at least 10 to 15 years.

Yoga lifestyle intervention reduces blood pressure in HIV-infected adults with cardiovascular disease risk factors.Cade WT et al. HIV Med. 2010 Jan 5.People living with HIV infection are at increased risk for developing cardiovascular disease (CVD). Safe and effective interventions for lowering CVD risk in HIV infection are high priorities. This pro-spective, randomised, controlled study evaluated whether a yoga lifestyle intervention improves CVD risk factors, virological or immunological status, or quality of life (QOL) in HIV-infected adults relative to standard of care treatment in a matched control group. Sixty HIV-infected adults with mild-moderate CVD risk were assigned to 20 weeks of supervised yoga practice or standard of care treatment. Baseline and week 20 measures were 2-h oral glucose tolerance test with insulin monitoring, body composition, fasting serum lipid/lipoprotein profile, resting blood pressures, CD4 T-cell count and plasma HIV RNA. Resting systolic and diastolic blood pressures improved more (P< 0.04) in the yoga group than in the standard of care group. However, there was no significant difference in body weight, fat mass, proatherogenic lipids, glucose tolerance or over-all QOL. Immune and virological status was not adversely affected. Yoga is a low-cost, simple to administer, nonpharmacological, popular behav-ioural intervention that can lower blood pressure in pre-hypertensive HIV-infected adults with mild-moderate CVD risk factors.

selection of peer-reviewed literature on preventive medicineThe number of peer-reviewed papers covering the vast field of preventive medicine is huge, to such an extent that it is frequently difficult for healthcare pro-fessionals to keep up with the literature. As a special service to our readers, iHE presents a few key literature abstracts from the clinical and scientific literature chosen by our editorial board as being particularly worthy of attention.


Wireless vital signs monitorA non-intrusive, body-worn wireless vital signs monitor that delivers real-time, high-quality data for healthcare applications has been introduced to the Euro-pean market. The Sen-sium Life Pebble from Toumaz Technologies

is an ultra small, ultra-low power body-worn device that continuously monitors common vital signs – including ECG, heart rate, skin tempera-ture and physical activity – and streams data over a short range wireless link to a Sensium USB Network Adapter. The acquired clinical quality data are ready for incorporation into an electronic health record. Simple to use and robust in operation, the Life Pebble provides a powerful and flexible solution for physiological monitoring, including continuous vital sign studies, rehabilitation and assisted living programmes, and in pro-fessional sports applications. The Life Pebble is based on new generation Sensium wireless technology that has been specifically designed for Body Area Networks (BANs) and non-intrusive physiological monitoring.

ToumAz TEChnologyAbingdon, oxon, uK www.ihe-online.com & search 45535

Patient monitoring platform integrated with hospital information systems

Unlike traditional patient monitors, the CARESCAPE Monitor B850 directly links hospital networks, electronic med-ical records (EMRs), diagnostic images, lab results and third-party devices with real-time patient monitoring data, to support efficient clinical decision-mak-ing. This enables the monitor to inte-grate its continuous clinical measure-ments with other elements of the patient record, delivering it at the point of care. The new monitor can be customized to

meet a variety of clinical needs. For example: • ECG — the B850 not only enables ‘cart-less’ diagnostic ECGs at the

bedside, but also exchanges data with the ECG repository, so facilitat-ing ECG analysis and comparisons to the patient’s prior ECG.

• Anesthetics — historically anesthetics have been administered without real-time, integrated anesthetic management tools because anesthesia delivery and patient monitoring systems are often ineffectively inte-grated. The enw system analyses drug therapy information to model and predict the effect of anesthesia-related drugs and drug interactions.

• Diagnostic images, lab information & more — the new monitor enables bed-side viewing of hospital EMRs, as well as X-rays, labs and other diagnostic reports, including the associated diagnoses from hospital experts.

gE hEAlThCAREhelsinki, Finland www.ihe-online.com & search 45536

Monitor with double A BHS ratingA detailed clinical study has proven that the NiBP technology used in the Compact 750 and 1000 series of patient monitors from Huntleigh Diagnostics qualifies for the double A rating according to the British

Hypertension Society (BHS) protocol. In order to achieve an A rating, at least 60% of the meas-urements must have a deviation of ≤ 5mmHg with regards to the ref-erence measurement. In fact the results of the study showed that 91%

of systolic measurements and 92.6% of diastolic measurements satis-fied this criterion. The smartsigns Compact 1000 series is a modular patient monitor which displays patient information on a high resolution 10.4” TFT display. The flexibility of the system means that clinicians can access a comprehensive set of invasive and non invasive measurements. The systems are ideal for emergency departments and specialist areas throughout the hospital.

hunTlEigh Cardiff, uK www.ihe-online.com & search 45537

ProdUcT HigHLigHT: moniTors 31 – Issue N°1 – Feb./Mar. 2010

To register, please call 800-767-9499. To learn more, pleasevisit ww.worldhealthcarecongress.com

The 7th Annual

April 12-14, 2010Gaylord National Resort and Convention Center

Washington, DC

Preliminary Agenda FeaturesEmerging Themes Including:

World HealthCare Congress

Employer Incentives and Preventionfor Improved Productivity

New Models for Health Plan,Hospital and Health SystemCollaboration

Implications of Health Reform on AllSectors in Health Care

Meaningful Use and the Deploymentof Health IT

Antimicrobial-treated castors Nosocomial infections are a serious cause of con-cern. In hospitals world-wide, recovery is often delayed because patients succumb to bacterial, viral and fungal infections. Strict hygienic direc-tives in hospitals and care homes are therefore necessary to avoid disease outbreaks. To comply with these directives, surfaces of hospital equip-ment are treated with antibacterial compounds to inhibit bacterial growth.However, antibacte-rial agents exclusively combat bacteria, whereas antimicrobials affect a variety of different

pathogens includ-ing bacteria, viruses, fungi and algae. TENTE-ROLLEN is now offering hos-pital bed castors treated with antimi-crobials. The cover caps of hospital bed castor series 2040 INTEGRAL and 2070 COVER DESIGN incorporate antimicro-bial compounds, detailed tests have confirmed that this successfully inhibits microbial growth.

TEnTE-RollEn gmbhWermelskirchen, germany www.ihe-online.com & search 45528

Mobile and flexible operating tableFull motorisation of surgical tables, standard in many high-end models, can considerably reduce the effort demanded of the surgical staff, but the cost can be prohibitive. TRUMPF offers an afford-able alternative to high-end operating tables. The Saturn Select mobile unit can be used in any sur-gical discipline and is easy to handle. Featuring

an electrically adjustable column and manually adjustable table top as the basis, the design has been further enhanced. Pneumatic springs allow the back and leg plates to be positioned without undue exertion. This also enhances safety when

positioning the patient. The patient may rest on either the Comfort Plus upholstery or the optional viscoelastic FoamLine pads that have excellent pressure-relieving properties. Thanks to the gen-erous leg room the traveling base offers, the medi-cal team can assume a comfortable and relaxed posture while working close to the patient. Large double-swivel castors allow the table to be moved easily, even on soft or uneven floors, carrying patients weighing up to 225 kilograms. A motor raises the column to the desired height, respond-ing to a remote control module or a keypad on the column itself. A low-height version of the table can be lowered to just 600 millimeters high.

TRumpF gRoupDitzingen, germany www.ihe-online.com & search 45530

High performance otoscopes and ophthalmoscopesDeveloped with input from medical doctors to ensure optical quality and an ergonomic design that is comfortable and user-friendly, the recently launched ri-scope L otoscopes and ophthalmo-scopes are high performance diagnostic instru-ments. All E.N.T. instruments of this series feature LED technology, which provides a whiter light, improving examinations due to enhanced image clarity and colour contrast. Lamps with LED tech-nology have a lifetime of at least 10,000 hours, compared to 20-30 hours with the alternative halogen and xenon lamps. Combining energy effi-cient LED technology with a long lasting lithium-ion battery, sustained high-power performance with significant cost savings is achieved. Light-weight lithium-ion batteries have a considerably higher charging capacity and longer lifetime than

regular batteries. In addition the company’s rheo-tronic technology for instrument handles allows all instrument heads in the series to be powered electronically by either LEDs or conventional bulbs from one handle. 100% light output is guaranteed immediately after a slight turn of the switch; it is possible to regulate light intensity very smoothly in both directions. An automatic turn-off function after 120s guarantees that LEDs, bulbs and the Li-Ion rechargeable batteries are conserved and can be used as long as possible.

RuDolF RiESTER gmbhJungingen, germany www.ihe-online.com & search 45532

ProdUcT nEWs32 – Issue N°1 – Feb./Mar. 2010

Cardiostim / Reed Expositions FranceTel.: +33 (0)1 47 56 24 56 - Fax: +33 (0)1 47 56 24 55 [email protected] Vista - 52-54, quai de Dion-Bouton - CS80001 92806 Puteaux Cedex - France

Early Fee Registration April 5, 2010

Scientifi c & Organizing Committee Philippe Ritter (Bordeaux, FRA)Pierre Bordachar, Stéphane Garrigue, Sylvain Reuter, Frédéric Sacher (Bordeaux, FRA), Mark O’Neill (London, GBR),Vincent Probst (Nantes, FRA), David Hayes (Rochester, USA), J.Claude Daubert (Rennes, FRA), Douglas Zipes (Indianapolis, USA),J.Jacques Blanc (Brest, FRA)

In collaboration with

RegisterNow !

17th World Congressin Cardiac Electrophysiology & Cardiac Techniques

June 16-19, 2010Nice Acropolis • French Riviera

www.cardiostim.fr

pubcom136x86.indd 1 3/02/10 16:18:58

FronT covEr ProdUcTRadiography Quality Assurance

A new X-ray meter is available for radiographic quality assurance applications. The Unfors ThinX RAD is optimised to meet the need for a basic multi-parameter instrument that simul-taneously measures dose, dose rate, kVp, HVL, exposure time and pulses. All parameters are conveniently displayed on the large LCD of the user-friendly instrument. A major advantage is that the meter provides a fully automatic user interface, without keys, including beam quality corrections. Only positioning and exposing is necessary to obtain rapid results.

unFoRSbilldal, Sweden www.ihe-online.com & search 45529

ProdUcT nEWs 33

Carestream present at two major upcoming exhibitions ECR 2010, 4 - 8 March, Vienna

At ECR 2010 Carestream will show upgrades to its latest PACS that include an embedded reporting module and a convenient graphic display for “at a glance” viewing of available patient records and data. The company will also show its new RIS that supports a secure Web portal enabling patients to reschedule an imag-ing appointment and centralised scheduling for multiple imaging sites. Time-saving new report-ing features include voice driven commands, structured reporting, standard answers and the ability to copy content from prior reports. The company’s innovative SuperPACS Architec-ture, which links multiple vendor RIS/PACS, will be showcased. It enables facilities to create workflow efficiencies through a global work-list across the enterprise, and its PowerViewer dramatically improves radiologist productivity for viewing 3D exams. The company will also launch an enhanced vendor-neutral archiving solution for images and data that is available in on-site or off-site configurations.

World of Health IT, 15 - 18 March, Barcelona, During the World of Health IT symposium, Carestream Health will participate in an Industrial Solution Session entitled “How a radiology cloud infrastructure supports a vari-ety of customer workflows; from emergency teleradiology to hospital cross reading and long term archiving”. In addition to this sym-posium, on the show floor Carestream Health will highlight an enhanced vendor neutral archiving solution that delivers consolidated data storage and management for any data type, regardless of vendor. It enables health-care providers to bring disparate PACS and a wide variety of DICOM and non-DICOM data sources from multiple sites into a shared, long-term data management solution that can streamline management tasks and reduce costs. Similar functionality is also offered as a service so that there is no equipment cost for the medical facility.

CARESTREAm hEAlTh Rochester, ny, uSA www.ihe-online.com & search 45531



FronT covEr ProdUcTFunctional imaging forinterventional neuroradiology

The syngo Neuro PBV IR software suite from Siemens Healthcare displays cerebral blood flow during interventional proce-dures and for the first time allows review of parenchymal blood flow during minimally invasive interventions in the brain. This feature assists the neuroradiologist in the treatment of stroke patients by displaying the condition of the cerebral tissue directly in the angio suite. According to the World Health Organization (WHO), approxi-mately 15 million people suffer from stroke every year. The earlier a stroke is treated, the larger the chance that as little brain tissue as possible is destroyed. The new software further shortens the time from diagnosis to treatment by directly display-ing the status of the cerebral tissue during minimally invasive procedures. Such tech-niques generally involve the use of a thin catheter within the arteries of the brain to either deliver a drug to dissolve the blood clot or a special catheter to mechanically remove it. Syngo Neuro PBV IR for the first time provides neuroradiologists with real-time information about the status of the brain tissue during minimally invasive procedures. This not only results in clini-cal advantages for stroke treatment, but is equally helpful for tumor biopsy and treat-ment, tissue embolization, and vasospasm therapy (spasms of blood vessels). Another benefit of the new software is that it is capa-ble of providing blood volume data for the whole brain, unlike traditional CT acquisi-tion, and allows the clinician to review the information from any orientation such as axial, coronal or sagittal.

SiEmEnSErlangen, germany www.ihe-online.com & search 45538

World of Health IT and eHealth week 2010For the first time ever, the EU’s high level eHealth Conference 2010 will be held together with the World of Health IT (WoHIT) conference and exhibition to form a eHealth Week 2010 at Barcelona, from 15th to 18th March. The chal-lenge for the many thought leaders who will be attending is to imagine a world where a patient doesn’t need to travel to see a doctor, but rather that the doctor would come electronically to the patient. Such a scenario is considered a fantasy by many, but the internet and in particular Social Media (also known as Web 2.0) are right now dramatically transforming traditional health-care practices. Unlike traditional websites, Web 2.0 applications allow people to interact, share experiences and knowledge. Could Twit-

ter and Facebook replace a physical doctor-patient consultation? There are of course many downsides

with Health 2.0 applications, such as data secu-rity, credibility of sources and privacy. eHealth Week 2010 offers an ideal forum for practition-ers, users, government leaders and decision makers to discuss these pressing topics.www.worldofhealthit.org

Replacement CT and conventional X-ray tubes Imaging departments face the never ending burden of reducing operating costs while prolonging equip-ment functionality. Designed to perform better, last longer and cost less than the original, the full line of replacement tubes from Dunlee includes over sev-enty CT replacements and over fifty conventional X-ray replacements, suitable for nearly every system from nearly every manufacturer. The tubes meet or

exceed original OEM specifica-tions with war-ranty conditions that are second to none. Dunlee products manu-

factures replacement tubes for more CT systems than any other company in the industry.

DunlEE mEDiCAl ComponEnTSbest, The netherlands www.ihe-online.com & search 45540

Patient height and weight measured wherever required

The new “3 in 1” ARNOLD system from CAE allows two patient parameters to be measured at any location in the healthcare facility using the same system. The param-eters are: a) the weight of the patient — which can be meas-ured equally well with the patient either in a standing

position or in a sitting position and b) the patient’s height, which is measured using a new telescopic electronic height rod. The system is robust, ergo-nomic and extremely mobile (even when fitted with its many optional accessories such as a printer) so that patients can be measured wherever desired. In the standing position, the patient can hold on to the back-rest or the retractable arm-rests without affecting the accuracy of the weighing. Easy to use and to maintain, the system has a capacity of 200 kg or 300 kg with an accuracy of 50g or 100g.

CAE Tenneville, belgium www.ihe-online.com & search 45539

ProdUcT nEWs34 – Issue N°1 – Feb./Mar. 2010

FronT covEr ProdUcTPowerful hand carried ultrasound system

At only 8.9Kg, the Sonoscape s8 is an extremely powerful hand carried port-able ultrasound system that offers all the features and functionality of large ‘cart-based’

high end systems in a portable ‘hand- car-ried’ package. The expansive digital beam-former lies at the heart of the imaging engine which provides exceptional image quality and the dual processor technology supported by the ultra-stable LINUX oper-ating software ensures high speed operation and reliability. The instrument is equipped with a large 15 inch high resolution colour LCD monitor and an intuitive operating pane. The system can be configured for all ultrasound imaging applications.

SonoSCApE Shenzhen, China www.ihe-online.com & search 45541

cALEndAr oF EvEnTsMarch 15-18, 2010World of Health IT Conference & ExhibitionBarcelona, SpainTel. +32 2 793 76 37Fax +32 2 793 76 31e-mail: [email protected] www.worldofhealthit.org

March 18-21, 2010KIMES 2010Seoul, KoreaTel. +82 (2) 551 0102Fax +82 (2) 551 0103e-mail: [email protected]

April 6-9, 2010Salon de la Santé 2010Casablanca, Moroccoe-mail: [email protected]

April 14-16, 2010Med-e-Tel 2010Luxembourg, LuxembourgTel. +32 2 269 84 56Fax +32 2 269 79 53e-mail: [email protected]

April 18-21, 201063rd CMEF Spring 2010Shenzhen, ChinaTel. +86 10 6202 8899 ext 3825Fax +86 20 6235 9314e-mail: [email protected]://en.cmef.com.cn

April 20-23, 2010Global Patient Safety SummitNice, FranceTel. +44 20 7383 6241 / 6281Fax +44 20 7554 6997http://internationalforum.bmj.com/2010-forum/global-patient-safety-summit

May 11-13, 2010Medical Fair Australia 2010Sydney, AustraliaTel. +1 312 781 5180Fax +1 312 781 5188e-mail: [email protected]/shows/ medfairaustralia.html

May 19-20, 2010World Health Care Congress - Europe 2010Brussels, BelgiumTel. +1 800 767 9499Fax +1 781 939 2692e-mail: [email protected] www.worldcongress.com/europe

May 25-28, 2010Hospitalar 2010São Paulo, Brazilwww.hospitalar.com/ingles/

June 7-9, 2010UKRC 2010 Birmingham, UKTel. +44 20 7307 1410

e-mail: [email protected]

June 12-15, 2010Euroanaesthesia 2010Helsinki, FinlandTel. +32-2-743 3290Fax +32-2-743 3298e-mail: [email protected] www.euroanaesthesia.com

June 16-19, 2010World Congress of Cardiology Scientific Sessions 2010Featuring the 3rd International Conference on Women, Heart Disease and StrokeBeijing, Chinae-mail: [email protected]

June 16-19, 2010CARDIOSTIM 201017th World Congress in Cardiac Electrophysiology & Cardiac TechniquesNice, Francewww.cardiostim.fr

Aug. 28 – Sept. 1, 2010ESC Congress 2010Stockholm, SwedenTel. +33 492 947 600Fax +33 492 947 601www.escardio.org/congresses/esc-2010

September 15-17, 2010Medical Fair Asia 2010Suntec SingaporeTel: + 65 6332 9620Fax: +65 6332 9655 / 6337 4633e-mail: [email protected]

October 9-13, 201023rd ESICM Annual CongressBarcelona, SpainTel. +32 2 559 03 55Fax +32 2 527 00 62e-mail: [email protected]

November 17-20, 2010MEDICADüsseldorf, Germanye-mail: [email protected]

Nov. 28 – Dec. 3, 2010RSNA 2010Chicago, IL, USATel. +1 630 571 2670www.rsna.org

dates and descriptions of future events have been obtained from usually reliable official

industrial sources. iHE cannot be held respon-sible for errors, changes or cancellations.

For more events see www.ihe-online.com/events/

www.worldcardiocongress.org

World Congress of CardiologyScientific Sessions 2010Featuring the 3rd International Conference on Women, Heart Disease and Stroke

16 –19 June 2010 | Beijing, China

世界心脏病学大会 2010暨第三届国际妇女心脏病和脑卒中学术会议, 中华医学会第十二次全国心血管病学术会议

2010年6月16日– 19日|中国北京

WCC_advert_210x276_EngChinese_mq3.indd 1 11.5.2009 11:23:41

Evolving care starts with evolving how you get your information.

GE Healthcare

CARESCAPE™ Monitor B850 now in ISICEM 2010.

See more at GE Healthcare booth 1.40, in Hall 1.

© 2010 General Electric Company - All rights reserved M1192645, 02/10, GE and GE monogram are trademarks of General Electric Company. GE Healthcare Finland Oy, doing business as GE Healthcare.

The new CARESCAPE™ Monitor B850 provides caregivers a unique level of integration

between patient monitoring data and hospital information systems. Unlike traditional patient

monitors, CARESCAPE Monitor B850 directly links hospital networks, electronic medical

records (EMRs), diagnostic images, lab results and third-party devices with real-time patient

monitoring data, to support efficient clinical decision-making at the point of care.

The CARESCAPE Monitor B850 from GE Healthcare brings together the strong clinical

heritage of Datex-Ohmeda’s anesthesia and Marquette Electronics’ cardiac expertise.

GE’s component innovation strategy provides for an unprecedented level of backwards

compatibility, allowing hospitals to leverage prior technology investments while updating

monitors in the areas of strongest clinical need.

www.gehealthcare.com


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