Contrast enhanced agents have been key to enhancing the diagnostic capability of computed tomography (CT), magnetic resonance imaging (MRI) and clinical radiography. Since the turn of the millennium, contrast enhancement for ultrasound (CEUS) has also emerged as an imaging tool. Along with developments in scanning hardware, new contrast agents have expanded the application envelope of ultrasound. During CEUS, tiny liquid suspensions of biodegradable gas-filled microspheres (also known as ‘microbubbles’) are injected as tracer for microscopic ultrasound imaging examinations. The microbubbles are metabolized and expelled from the body within minutes. Clinical applications for ultrasound contrast agents potentially extend to any organ or physiological system that is evaluated with conventional ultrasound, with the singular exception of the fetus. As of now, major applications are in cardiac and hepatic imaging. Other applications are being explored, including paediatric CEUS.
From imaging complement to alternative
There is growing evidence that CEUS is valuable, accurate and cost-effective. It often complements CT and MRI, and in several instances, has become an important alternative to either. This especially concerns patients with renal failure, those who wish to avoid the radiation risk of CT or cannot cope with being shut inside a scanner.
Interest in CEUS has grown sharply since 2016, after the Food and Drug Administration (FDA) approved a microbubble contrast agent for liver CEUS, paving the way for much faster growth in the US market.
The microvascular challenge
Clinically, one of the key drivers for CEUS has been limits to the performance of ultrasound imaging and Doppler techniques. While B-Mode provides anatomical information, Doppler allows for visualization of the larger vessels in the macrovascular system, based on the velocity of blood flow in the intravascular lumen. However, there are limits to both spatial resolution and Doppler sensitivity.
The utility of conventional ultrasound reduces rapidly when a clinician needs to visualise smaller vessels and capillaries, lying within deeper structures of the body’s microvascular system.
To achieve this, and more specifically, determine differences in arrival-, dwell- and wash-out time within specific regions of parenchymal tissue, there is a need for direct imaging via tracers. It is in this capacity that contrast agents play a useful role. They improve the sensitivity and specificity of ultrasound and greatly expand its scope for application.
The advantages of CEUS
CEUS has certain intrinsic advantages when compared to other imaging modalities.
It permits ultra-high temporal imaging of contrast enhancement profiles at between 20 and 50 images per second, for a duration of about 5-8 minutes. This makes it possible for continuous visualization of images in all phases – from the early arterial to the late phase – and seek to ensure no patterns are missed. CEUS also allows for both follow-up examinations at short intervals, and, given its lack of ionising radiation, for repeated examinations over a long period of time – a common requirement for chronic diseases. CEUS is also convenient. It can be used at multiple bedsite locations – from intensive care units (ICUs) and operating rooms to recovery rooms and ambulatory units.
Contrast agents for ultrasound have been found to be safe with no cardio-, hepato-, or nephro-toxic effects. Laboratory checks to assess liver, renal or thyroid function before administration are therefore not required.
Evaluating liver lesions
In the liver, CEUS has proven its utility when clinicians encounter focal lesions during cross-sectional imaging of an asymptomatic patient. Though most such collateral encounters are benign, it is necessary to pursue dedicated imaging characterization and diagnosis, in order to exclude malignancy. This is especially true when the lesions are large or otherwise atypical and when the patient is from a high-risk group.
Traditionally, the evaluation of lesions was undertaken with magnetic resonance imaging (MRI) or multiphase CT. However, the former was generally limited in availability, while multiphase CT invoked concerns about radiation. CEUS is seen to be safe, non-invasive and available.
When CEUS is used in the liver, microbubble delivery occurs via two routes, namely the hepatic artery and portal vein. Blood flow through the latter needs to first transit gastrointestinal circulation, and therefore arrives at a later time point. This permits differentiation between the two wash-in phases.
CEUS enhances the display of vascularity in liver lesions, and is both accurate and reproducible. The vascular supply for focal liver lesions is characteristic of a particular lesion type and different from normal liver tissue. While abnormal vascularity of hepatocellular carcinoma can be demonstrated early during the contrast inflow phase, metastases are characterised in the late phase. In addition, the timing and the intensity of washout can differentiate hepatocellular malignancies from non-hepatocellular ones. The former demonstrate delayed and weak washout. Non-hepatocellular tumours show strong, early washout.
The need for right dosing
Using the optimal dose is important. Too high a contrast agent dose results in artefacts, particularly in the early phases of enhancement. These include acoustic shadowing, over-enhancement of small structures and signal saturation, which is also detrimental for quantification.
On the other hand, a low dosage causes the concentration of microbubbles to be sub-diagnostic in the late phase, challenging the detection of wash out.
If the wash out is early, the dose was probably too low. Here, it can be important to evaluate the status of the liver as being healthy or diseased. In difficult cases, a second (higher) dose may be administered, with no or only limited scanning in the early phases to reduce bubble destruction. The exact dose depends on the contrast agent, ultrasound equipment (software version, transducer), type of examination, organ and target lesion, size and age of the patient.
Other challenges for CEUS in the liver
Apart from the challenge of dosing, there are other limitations too in the use of CEUS in the liver. Very small lesions may be overlooked. The smallest detectable lesions are considered to be 3-5 mm in diameter.
There are also some specific shortcomings, such as fat layers surrounding the falciform ligament. These can cause enhancement defects which might be confused with a lesion.
Given limits to penetration, deep-seated lesions may also not always be accessible. However, some clinicians suggest that bringing the liver closer to the transducer via use of left lateral decubitus positioning can overcome such a limitation.
CEUS and cardiology
CEUS has also shown remarkable utility in cardiology. After the tracer injection, micro-bubbles follow the flow and distribution of red blood cells. opacify the cardiac chambers and enhance delineation of the left ventricular border. The microbubbles are then ejected into the arterial circulatory system, allowing for visualization of blood flow into the parenchymal organs.
An assessment of cardiac function depends on proper delineation of the endocardial border and wall motion patterns. This is where conventional ultrasound faces serious limits. Intracardiac echo reflections couple to weak signals from structures in parallel to the echo beam. The ensuing delineation of the endocardial border can therefore be unclear, resulting in an inaccurate left ventricle assessment.
What contrast agents achieve here is to completely fill the ventricular cavity, and thereby delineate it in a similar fashion to cardiac MRI.
Proper assessment of cardiac function is especially important for stress echo tests in order to demonstrate inducible ischaemia. Here, the risk of a stress examination means that inadequate image quality is unacceptable. In addition, precise delineation of the cardiac chamber is required to make an assessment of heart insufficiency and decide on whether an automatic implantable cardioverter defibrillator (AICD) is indicated. Such precision is also required with cancer chemotherapy patients, in order to assess cardiotoxicity.
New contrast agents
First-generation ultrasound contrast agents were based on air, which was sufficiently soluble in blood for use with the equipment of the time. Second-generation agents contain an inert lipophilic gas with very low solubility, thus avoiding early leakage of the gas. This provides more stability to the microbubbles.
Modern contrast agents have a shell made out of a thin and flexible phospholipid membrane. One side, which faces the surrounding blood, has hydrophilic properties. On the other, lipophilic chains make contact with the encapsulated gas.
Over recent years, technology development has focused on ultrasound contrast agents which reduce microbubble size and increase persistence within the blood in the circulatory system, to 10 or more minutes. Researchers are also seeking to develop new materials and gases to control the encapsulating shell or surface of the microbubble, in order to inhibit dissolution and diffusion.
Constraints faced by microbubbles
In spite of the above developments, there are some constraints with microbubbles.
They do not last long in circulation, due to being taken up by immune system cells, the liver or spleen. They also have low adhesion efficiency, which means only a small fraction bind to an area of interest. Microbubbles can also burst at low ultrasound frequencies and at high mechanical indices, which, in turn, can lead to local microvasculature ruptures and haemolysis.
Guidelines on CEUS
The use of CEUS varies widely from one country to another, and even between different healthcare facilities in the same country.
Guidelines were first issued for the use of CEUS for liver applications in 2004. They were updated in 2008, reflecting growth in the availability of contrast agents. CEUS has also been recommended in guidelines for several non-liver applications, under the auspices of EFSUMB.
The latest guidelines date to 2012. They are published under the auspices of the World Federation for Ultrasound in Medicine and Biology (WFUMB) and the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). The aim is to create standard protocols for CEUS in liver applications across the world.
According to the guidelines, CEUS is indicated for liver lesion characterization in the following clinical situations:
• Incidental findings on routine ultrasound
• Lesion(s) or suspected lesion(s) detected with US in patients with a known history of a malignancy, as an alternative to CT or MRI
• Need for a contrast study when CT and MRI contrast are contraindicated
• Inconclusive MRI/CT
• Inconclusive cytology/histology results
Paediatric applications
One new frontier for CEUS applications consist of children.
Currently, sulphur hexafluoride gas microbubbles have been approved by the FDA in the US for characterising focal liver lesions in children and vesico-ureteral reflux. In Europe, CEUS in children is indicated for vesico-ureteral reflux, although there is
significant off-label use too.
Though global maternal mortality has declined by 1.3 percent a year since 1990, the rate continues to remain stubbornly high in certain regions. At present, fewer than one of 50 pregnant women require critical care. However, both maternal and fetal mortality can be high when it is required.
In industrialized countries, the rate of obstetric ICU admissions varies from 50 to over 400 per 100,000 deliveries with an overall case-fatality rate of 2%. In developing countries, fatality in obstetric ICU patients can be 3-5 times higher.
Obstetric disorders in the ICU
Obstetric ICU patients include those with obstetric disorders as well as pregnant patients with medical/surgical disorders. The bulk of patients are admitted to the ICU for obstetric disorders. In general, obstetricians are aware of all obstetric patients in hospital, whether they have a medical or obstetric problem.
There are several obstetric conditions which can require ICU admission. The most common are hemorrhage and hypertensive disorders, above all pre-eclampsia toxemia (PET) and eclampsia. In industrialiZed Western countries, these typically account for 30-35% and 20% of admissions to the ICU.
Hemorrhage leading cause of mortality, ICU admission
Obstetric hemorrhage is either antepartum or postpartum, and remains the leading cause of maternal mortality. Antepartum hemorrhage occurs in 5 percent of pregnant women, and in the bulk of cases carries no risk to the mother or fetus. Major causes involve the placenta and uterine rupture.
Postpartum hemorrhage (PPH) is the single most frequent indication for ICU admission, and involves major blood loss, regardless of the mode of birth. Though there is no universally accepted definition, it typically means more than a half litre of blood loss within 24 hours. In about two out of three cases, PPH is due to failure of uterine contraction after delivery, with most of the rest caused by placental retention. Genital trauma, due to laceration of the vagina or cervix because of instrument delivery, is also increasingly implicated in PPH.
Patient management of obstetric hemorrhage depends on identifying the cause and whether or not delivery has occurred. In PPH, management is aggressive, beginning with administration of oxytocin, emptying of the bladder and massage of the uterus. The care team also begins intravenous prostaglandin therapy, coupled with uterine tamponade via balloon compression or packing. If bleeding persists, surgical intervention is indicated: arterial ligation, suture, Cesarean hysterectomy or uterine artery embolization. Should bleeding continue, recombinant factor VIIa is administered and repeated, if there is no response.
Hypertensive disorders
Pre-eclampsia toxemia (PET) occurs in 2 to 3 percent of all pregnancies after 20 weeks of gestation, and is classified as mild, moderate or severe. Its pathogenesis results from abnormal placenta formation, and it is characterized by impaired organ perfusion due to impaired vasodilation and placental ischemia. As pregnancy progresses, the ischemia worsens. This makes the mother hypertensive, with a risk of renal dysfunction.
Severe PET is associated with significant morbidity and mortality, both for the mother and fetus. It requires one or more of the following indicators: hypertension (BP over 160 systolic or 110 diastolic), proteinuria higher than 5 grams per 24 hours or oliguria below 400 ml per 24 hours, along with cerebral irritability, epigastric pain, and pulmonary edema.
PET usually resolves following delivery of the fetus but may manifest postpartum. A variety of antihypertensive agents, including hydralazine, labetalol, sodium nitroprusside, alpha blockers, calcium channel blockers and methyl dopa, have been advocated in PET. Hydralazine and labetalol are the most widely used in the critical care setting. Magnesium is usually co-administered to provide vasodilatation and prevent seizures. Care should be taken with fluid resuscitation because of the risk of pulmonary edema.
Eclampsia is an extreme complication of PET, and is marked by the occurrence of convulsions and seizures, 40% of which occur following delivery. The seizures tend to be self-limiting, with a very rare incidence of status epilepticus. Though the mortality from eclampsia has been high in the past, death is now uncommon. Common causes of mortality are hepatic complications, including hepatic failure, hemorrhage, or infarction.
Other challenges of pregnancy
Peripartum cardiomyopathy is another challenging condition during pregnancy, albeit of unknown cause. It is one of the leading causes of maternal death, with mortality as high as 25-50%. It can occur from the final month of pregnancy up to 5 months after delivery.
Other conditions unique to pregnancy include HELPP syndrome (hemolysis, elevated liver enzymes and low platelets), placental disorders (abruption, previa or retention), amniotic fluid embolism and chorioamnionitis, and acute fatty liver.
Changing epidemiology
The epidemiology of obstetrics in the ICU has changed dramatically since the past decade. Obstetric conditions such as thrombocytopenic purpura of pregnancy, which were rare in the past, are now being diagnosed more frequently. Massive hemorrhage from adherent placenta is increasing due to the growing number of pregnant women bearing scars from previous cesarean sections (CS). Uterine rupture during labour is also sometimes associated with previous CS. Another condition is ovarian hyper-stimulation syndrome, which is not uncommon any more due to the sharp growth in the availability of assisted reproduction techniques.
There are now many older mothers with pre-existing disorders and chronic medical conditions, some of which can be in an advanced stage. Typical co-morbidities today including essential hypertension, Type 2 diabetes and coronary heart disease. Obesity is also a major concern, which poses numerous challenges for managing pregnant patients in the ICU.
Impact on multiple physiological systems
Pregnancy affects several physiological systems – among them, the cardiovascular, respiratory, renal, hematologic and endocrine. These tax a patient’s reserves and often compromise responses needed to combat a disease state during pregnancy and the peripartum period.
Pregnancy’s impact on physiological systems is twofold: first, by worsening pre-existing conditions, and second, by heightening susceptibility.
For example, cardiovascular conditions which can deteriorate significantly in pregnancy include aortal coarctation, primary pulmonary hypertension and valvular disease; congenital heart disease is another such condition. Cardiovascular issues are also important since that shortness of breath is a very common symptom in pregnancy. When this occurs, clinicians must distinguish the dyspnea resulting from underlying medical disorders versus that caused by normal physiologic changes in pregnancy. The latter include anemia, upward displacement of the diaphragm, and respiratory alkalosis.
One of the most confounding cardiovascular challenges is associated with PET. Aside from hypertension, patients also show increased systemic vascular resistance and reduced intravascular volume, which cause a reduction in cardiac output as disease severity progresses. In such cases, left ventricular function can deteriorate leading to a risk of pulmonary edema after fluid resuscitation.
On the other side, pregnant women also face an increase in risk for a gamut of infections ranging from varicella pneumonia and urinary tract infections to malaria and hepatitis.
In the respiratory system, the impact of pregnancy on cystic fibrosis is well known. However, pregnant women also face a concurrent increase in susceptibility to venous embolisms and pulmonary thromboembolism.
This kind of dual impact is also faced by the renal, endocrinal and neurological systems. Pregnancy worsens renal insufficiency and glomerulonephritis and enhances susceptibility to acute renal failure.
In the endocrinal system, it worsens diabetes and prolactinoma and increases susceptibility to gestational diabetes.
The list of neurological conditions which deteriorate during pregnancy is especially large, and includes epilepsy, myasthena gravis and multiple sclerosis, while an increase in susceptibility is seen with intracranial hemorrhage. Another complicating factor is that up to half of obstetric critical care patients have some form of neurological compromise. In most circumstances, this is the result of their admission diagnosis (that is, pre-eclampsia or obstetric hemorrhage), rather than as the precipitant of their ICU admission.
Two patients in one
As a result of the above factors, obstetric critical care represents a major challenge for medical professionals. Obstetricians need to master both maternal and fetal physiology, and avoid any potentially adverse effects on a fetus of diagnostic and therapeutic interventions given as part of care for the mother. Indeed, it is a common statement that obstetricians treat two patients, the mother and the fetus. They must also assess two separate risks – maternal and fetal – from continuing with a pregnancy and decide if termination of the pregnancy improves the outcome for the mother. This is a very charged challenge since a fetus is generally robust despite maternal illness, and it has been demonstrated that pregnancy-induced critical illnesses are resolved by delivery of the fetus.
Mastering general principles
Obstetric ICU practice consists of firstly mastering general principles such as drug safety, ventilation and management of patient airways, monitoring of the fetus, muscle relaxation and sedation, cardiovascular support, thromboprophylaxis, as well as radiology and ethical issues. This is followed by the acquisition of expertise in the management of obstetric and medical conditions.
Critical care interventions for an obstetric patient are similar to those for the non-pregnant patient. However, it is often necessary to adjust physiologic targets for metabolic, pulmonary, and hemodynamic control.
The need for teamwork
Given the complexity and time-sensitiveness of critical care medicine, teamwork skills are essential. Typically, the care team for an obstetric patient at an ICU is multidisciplinary, consisting of the intensivist, obstetrician, anesthesiologist, maternal-fetal medicine specialist, the neonatologist and the ICU nurses. This team needs to operate effectively alongside regular staff.
Although clinicians working in critical care environments are generally highly trained and competent, they have traditionally not learned how to work well as part of a team. Remedying this has become a priority on both sides of the Atlantic.
As part of a paper on standards of care, the European Board and College of Obstetrics and Gynaecology (EBCOG) explicitly recommends “multidisciplinary, high-quality teamwork” as being “essential” in obstetric medical care and urges healthcare providers to ensure that maternity services have adequate facilities, expertise, capacity and back-up for “timely transfer to intensive care.” EBCOG also seeks to give substance to such a mission. It urges a system of “clear referral paths” to enable pregnant women requiring additional care to be managed and treated by the appropriate specialist teams when problems are identified. One of its most interesting recommendations is for development and routine use of an obstetric ‘early warning chart’ to help in the timely recognition, treatment and referral of women developing a critical illness.
Teamwork is also seen as being a priority in the US, where the Joint Commission pointed to failures in teamwork and communication as among the leading causes of adverse obstetric events. Although obstetric clinicians seem aware of deficiencies in teamwork, their perceptions of teamwork differ based upon their role. In a survey by Johns Hopkins University of 44 hospitals across the US, the majority had fewer than half of respondents reporting ‘good teamwork’ in their labour and delivery units.
As the threat of a COVID-19 pandemic stares us in the face, it may be opportune to consider some scenarios ahead, especially in light of lessons from other, similar outbreaks in recent decades.
The first problem is sporadic bursts of public concern, alternating with periods of denial. Managing both requires measured doses of reliable information from authoritative sources. Such measurement is a delicate art at the best of times. During a crisis, media hype can mutate it easily into mass misinformation.
Similarly, the threat of terrorism has close parallels with each of the above aspects.
The ICU (intensive care unit) is easily one of a hospital’s highest value resources. A scarcity of intensive care beds means patients require prioritization when demand exceeds supply. As a result, there are frequent delays in admission to an ICU. Though it is accepted that such delays adversely impact patient outcomes, there has been little data on the relationship between bed availability in an ICU and processes of care for patients who develop sudden clinical deterioration – especially in the context of an emergency department (ED). Recently, studies seeking to address this gap have provided renewed momentum to such discussions. They have also dovetailed with other efforts, such as specialist training in critical care for emergency medicine students and residents. However, the area generating maximum interest is a dedicated ICU within an emergency department.
Balancing needs, finding beds
Critically ill patients are commonplace in emergency medicine. They require aggressive and timely care, but emergency medicine clinicians have to balance their needs with those of other patients in their facility. In addition, due to constraints in beds in the ICU, increasing numbers of critically ill patients require to be boarded for prolonged periods of time in the ED. Adding to this problem is a shortage of beds in EDs too.
One of the most vexed questions is whether ED physicians consider bed availability in an ICU as part of their triage decisions, thereby impacting, in a potentially profound manner, on patient outcomes and resource utilization in both the ED and ICU. In effect, does a high availability of ICU beds lead to a bias in admission of patients who are either too well or too ill to benefit ? On the other side, does a low availability then lead to denying admission to ED patients, who would otherwise have been accepted to the ICU?
ED-ICU interface demands attention
In 2013, a study by the George Washington University School of Public Health and Health Sciences in Washington, DC, found that the volume of ICU admissions from EDs in the US had increased sharply, by almost 50 percent, in the period 2001-2009.1 During this period, another study found that the number of ICU beds across the country had increased only 15%, from 67,579 to 77,809.2
In other words, it is clear that ICU admissions from EDs have been increasing at a faster rate than ED visits. The George Washington University study found that though lengths of mean ED and hospital stays had not changed significantly, the mean ICU admission spends over 5 hours in the ED prior to transfer to an ICU bed. As a result, its authors concluded, there was a need for more emphasis on the ED-ICU interface and for critical care delivered in the ED.
Training emergency physicians in the ICU
The roots of this complex combination of challenges go back several decades. One good example is a time-based study, published in 1993 in the peer-reviewed journal ‘Critical Care Medicine’.3 The authors, from Houston, Texas-based Methodist Hospital’s Department of Emergency Services, noted that not only did critically ill patients “constitute an important proportion of emergency department practice”, but also needed treatment in the ED “for significant periods of time.” One of the solutions they proposed was for emergency medicine practitioners to “receive training in the continuing management of critically ill patients.”
The above approach was also witnessed in Europe. In Belgium, for example, an official paper from 1995, titled ‘How to become an intensivist’, proposes that a candidate with an “agreement in Emergency medicine has to make another year of ICU formation.”4
Pathways remained unclear
In subsequent years, there was significant growth in emergency medicine residents pursuing critical care fellowship training, and a reconsideration of the role played by the ED in caring for the critically ill. Nevertheless, there still was a lack of clarity in ways to acquire advanced training in critical care for emergency medicine residents.
In December 2002, an article in ‘Current Opinion in Critical Care’ complained that although ED care for critically ill patients was shown to significantly impact mortality, “formal critical care training for emergency physicians” was still “limited.”5
Less than three years later, another peer-reviewed journal, ‘Annals of Emergency Medicine’, noted that in spite of growing demand for critical care services, most critical care medicine fellowships did not accept emergency medicine residents, “and those who do successfully complete a fellowship do not have access to a US certification examination in critical care medicine.”6 The authors proposed “expansion of the J-1 visa waiver program for foreign medical graduates,” but said the only sensible long-term approach was to strengthen the relationship between emergency medicine and critical care medicine.
Critical care medicine as emergency medicine sub-specialty
In the US, the Accreditation Council for Graduate Medical Education (ACGME) approved critical care medicine as a sub-specialty for emergency medicine physicians in 2011. The following year, the surgical critical care fellowship pathway was approved for emergency physicians interested in becoming board-eligible intensivists.
Currently, the most common training pathways are via combinations of critical care medicine with internal medicine and anaesthesiology, and alongside surgical critical care and neurocritical care. Career pathways for physicians trained in emergency and critical care medicine are also evolving, with options in both community and academic settings.
The role of professional societies
Leading professional societies in emergency medicine and critical care have set up focused sections on the interface between the two areas to stimulate interest as well as provide support to medical students and residents.
Examples from the US include the Emergency Medicine Residents’ Association (EMRA), whose Critical Care Division maintains a comprehensive database of training opportunities across the country,7 and regularly publishes alerts on key developments in critical care. Another interesting initiative is the Coalition for Critical Care Medicine in the Emergency Department (C3MED), which was set up in 2003 and hosts an active email discussion forum.8
Similar efforts have been undertaken by the American College of Emergency Physicians (ACEP),9 the Society of Critical Care Medicine (SCCM),10 the American Association of Emergency Medicine11 and the Society for Academic Emergency Medicine (SAEM).12
In Europe, one of the best-known initiatives to harmonize convergence of the ED and the ICU is ISICEM, the International Symposium on Intensive Care and Emergency Medicine. This non-profit organization, headquartered in Brussels, was set up in 1980. It currently runs a series of eight annual events, covering different aspects of intensive care and emergency medicine. Over the years, participation has grown from about 200 to over 6,000 from more than 100 countries.
Impact of ED on ICU: US and European studies
There have also been concerted efforts to assess the impact of emergency department volume and boarding times on ICU admission and patient outcomes. Two recent studies have catalysed considerable new attention in the topic.
The first is a retrospective cohort study on critically-ill ED patients for whom a consult for medical ICU admission had been requested over a 21-month period. It was published in ‘Critical Care Medicine’ last year by a US-based team from the Icahn School of Medicine at Mount Sinai, New York, and titled ‘Effect of Emergency Department and ICU Occupancy on Admission Decisions and Outcomes for Critically Ill Patients’.
The authors conclude that ICU admission decisions for critically ill ED patients were affected by ICU bed availability. However, higher ED volume and other ICU occupancy did not play a role. They also found that prolonged ED boarding times were associated with worse patient outcomes, suggesting a need for improved throughput and targeted care for patients awaiting ICU admission.
In August 2019, ‘Critical Care Medicine’ published findings online from another study on this topic, this one by a Dutch team from six University Medical Centres at Amsterdam, Groningen, Leiden, Nijmegen, Rotterdam and Utrecht, along with the country’s National Intensive Care Evaluation (NICE) foundation.13 The retrospective observational cohort study conducted a registry analysis of 14,788 patients from the six hospitals, and found an association between emergency department to ICU time greater than 2.4 hours and increased hospital mortality after ICU admission
Ad-hoc and hybrid models
At present, there are two approaches to the challenge of intensive care in the ED. The more common is to have an emergency physician intensivist working standard ED shifts, and lending expertise on an ad-hoc basis to critically ill patients. A recent development is a ‘hybrid’ model. This earmarks a dedicated area of the emergency department for ramping up care to critically ill patients, with a dedicated physician providing intensive care only to such patients, typically for periods longer than an hour.
Supporters of the hybrid model state that it is easier and less expensive to establish with extra costs involving only the dedicated ED-ICU physician.
The ED-ICU
One of the most watched developments in recent years in care for critically ill patients in an ED is the development of ED-ICUs (emergency department intensive care units).
Two such facilities in the US, Stony Brook Resuscitation and Acute Critical Care Unit (RACC) in New York and Emergency Critical Care Center (EC3) in Michigan are considered as being both ED-ICU pioneers and best-of-class references for the concept.
EC3 is considered to be among the world’s most advanced emergency critical care centres. It was opened in February 2015 and has five resuscitation trauma bays and nine patient rooms, located adjacent to the main adult emergency department.
Due to this reputation, the case for ED-ICUs was strengthened after a recent study by EC3 found convincing improvements in survival as well as reduced inpatient ICU admissions.14 In effect, an ED-ICU can improve care and survival rates for the entire emergency department population.15
The EC3 study covered 350,000 ED patient encounters, and found that implementation of an ED-based ICU was associated with significant reductions in risk-adjusted 30-day mortality among patients, from 2.13 to 1.83 percent. The median time to ICU-level care for critically ill patients decreased from 5.3 hours to 3.4 hours, while the hospital ICU admission rate from the ED dropped from 3.2 percent to 2.8 percent.
References
1.https://www.sciencedaily.com/releases/2013/05/130514212946.htm2.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351597/3.https://www.ncbi.nlm.nih.gov/pubmed/8319477/4.http://www.siz.be/education/training-in-critical-care/5.https://www.ncbi.nlm.nih.gov/pubmed/124545496.https://pdfs.semanticscholar.org/4f1b/5cea333174e599784e6a2d80c9b55b868b2e.pdf7.https://www.emra.org/fellowships/critical-care-fellowships/8.c3med@yahoogroups.com9.https://www.acep.org/criticalcaresection/10.http://www.sccm.org/Member-Center/Sections/Pages/Emergency-Medicine.aspx11.http://www.aaem.org/membership/critical-care-section12.https://community.saem.org/communities/community-home?CommunityKey=5dc206d8-d248-4f71-aecd-e0490cdc3ba913.https://insights.ovid.com/pubmed?pmid=3139332114.https://jamanetwork.com/journals/jamanetworkopen/fullarticle/273862515.https://medicalxpress.com/news/2019-07-department-based-intensive-patient-survival.html
Point-of-care testing (POCT) is typically described as a clinical test which is done at, or close to, the physical location of a patient. This could be at a patient’s home, in a pharmacy, a GP’s office or an in-hospital bed site. POCT typically consists of portable devices and instruments, which return results quickly. As a result, POCT permits immediate intervention or treatment.
POCT can also be defined usefully by specifying what it is not. In this case, a POCT is simply a test that is not analysed in a laboratory. POCT short circuits many steps involved in the latter. It eliminates the need to collect a specimen, transfer it to the lab, perform the test, and transmit results back to the provider.
POCT is increasingly used to diagnose and manage a range of diseases, from chronic conditions such as diabetes to acute coronary syndrome (ACS). Recent additions include genetic tests.
Driven by miniaturisation
The POCT era is considered to have begun in the 1970s, with a test to measure blood glucose levels during cardiovascular surgery. In 1977, a rapid pregnancy test called ‘epf’ became the first POCT for use wholly outside a hospital.
Since the late 1980s, one of the key drivers of POCT has been product miniaturization, with increasingly sophisticated and ever-smaller mechanical and electrical components integrated onto chips that can analyse biological objects at the microscale. The pace of miniaturization has accelerated at a breakneck speed in recent years, to mobile handheld and wearable POCT devices. These can be inte-
grated with other applications within a healthcare facility, or aid patients in monitoring and self-management of chronic conditions.
Wide product range, but handful of tests dominate
The most widely-used POCTs include “blood glucose testing, blood gas and electro-
lytes analysis, rapid coagulation testing, rapid cardiac markers diagnostics, drugs of abuse screening, urine strips testing, pregnancy testing, faecal occult blood analysis, food pathogens screening, haemoglobin diagnostics, infectious disease testing and cholesterol screening.” Nevertheless, just three tests – urinalysis by dipstick, blood glucose and urine pregnancy – are believed to account for the majority of POCT.
Comparisons with the lab
Beyond definition, the relationship of POCT to a laboratory is close for a very good reason. Most clinical cases for POCT use lab testing as a comparator. In other words, the first question that comes to many people when using POCT is whether its results match those of a laboratory. Although evidently quicker to obtain, is POCT as reliable? Another topic for comparison consists of the cost of POCT versus lab tests.
Costs: a vexed question
Even in the heady early days of POCT, there was awareness about potential cost downsides. One of the first efforts to address this question was a US study, published in 1994 in ‘Clinical Therapeutics’. [1] The study, by the Office of Health Policy and Clinical Outcomes at the Thomas Jefferson University Hospital in Philadelphia, sought to determine time and labour costs for POCT versus central laboratory testing on a cohort of 210 patients presenting to the emergency department.
The patients had blood drawn for a Chem-7 profile (sodium, potassium, chloride, carbon dioxide, blood urea nitrogen, glucose, and creatinine), or for cell blood count (CBC). Largely due to much quicker turnaround time (TAT), physicians reported that POCT would have resulted in earlier therapeutic action for 40 of 210, or 19 percent of patients. Costs for POCT were, however, over 50 percent higher, and also showed significant variability, depending on test volume. The authors speculated that increasing volumes of POCT would reduce costs “substantially.”
Volumes lower cost
The perception that POCT is much more expensive than a centralized laboratory persists. There are several reasons for this. Consumables generally cost more than tests done with automated laboratory instruments. On its part, POCT simply cannot achieve the scale economy associated with the latter. It also requires more staff downtime.
However, right from the early stages of POCT use, it seemed likely that unit costs could be reduced by increasing test volumes, as anticipated in the 1994 study by Jefferson University Hospital.
POCT was also to quickly demonstrate enhanced utility for certain kinds of tests. In 1997, a study at an Indiana hospital reported a near-halving in unit costs of panels, from USD 15.33 to USD 8.03, following POCT implementation for blood gases and electrolytes [2].
Levelling the field of play
One of the biggest hurdles in making cost comparisons of POCT with lab tests is the difficulty of levelling the playing field. It is also difficult to use such an exercise to draw generalised conclusions, since key conditions often vary significantly from one care facility to another. POCT is also complex to manage, and it is especially challenging to maintain regulatory compliance, especially in large institutions.
Though the cost of consumables is straightforward to determine, this is hardly so for labour.
Labour costs for a lab test are not limited to staff in the laboratory. They also include costs of staff in the pre-analysis phase, for phlebotomy, nursing and other services. Many of the latter entail administrative overheads. Typically, these would consist of formalities in the collection of phlebotomy supplies, the completion and submission of a test request, the labelling of tubes, specimen packaging and despatch.
In contrast, POCT eliminates most pre-analytic steps, along with associated staff costs and overheads. POCT can be undertaken by personnel who are not trained in clinical laboratory sciences.
Cost versus value
Although it seems to be common sense that POCT labour costs are significantly less than for a laboratory test, calculating this precisely requires a complex time-and-motion study which takes account of differences in wages and other costs for phlebotomists, nurses, administrative staff and medical technologists.
Unit product cost therefore reflects only a part of the overall equation, as far as justifying the case for a test is concerned. Indeed, many experts now urge for making assessments based on unit value rather than unit cost.
The role of TAT
With POCT, faster TAT promises better treatment, reduced patient stay, superior workflow and improved clinical outcomes. POCT is however less about reducing TAT than making results available in an optimal and clinically relevant time frame. This, in turn, is frequently dictated by conditions for which care is targeted as well as the setting in which it is delivered.
Delayed test results also impact upon cost in indirect ways. For instance, radiology departments use creatinine POCT before administering contrast agents, since patients with impaired renal function can develop contrast-induced kidney injury. This allows for quick decisions about patients and efficient use of costly CT scanners. If physicians had to wait for test results from a laboratory, the scanner would risk having to idle in a stand by status.
POCT can sometimes be only choice
Some tests have to be performed at point of care since there is no choice, in terms of time for transport to a lab.
One good example is an activated clotting-time test. This is used to monitor cardiac patients undergoing high-dose heparin therapy, whose blood immediately starts to clot after collection of a sample. Another is a POCT glucose test, where a quick result is crucial in determining insulin dosage for diabetic patients.
Elsewhere, whole blood cardiac-marker POCT tests in an A&E facility allow physicians to make rapid decisions on patients with acute coronary syndromes in terms of triage and disposition for observation, catheterization or transfer to a cardiac ICU.
Yet another example is a rapid flu test, used to identify patients who could benefit from antiviral therapy requiring administration as soon as possible after infection, in order to reduce symptomatic intervals. None of the above permit the wait times required for a lab test.
The grey zones
Still, there are grey zones where lab tests have advantages, which are non-negotiable under certain conditions.
One example is routine monitoring of international normalized ratios (INR) for patients on warfarin. The latter is used for prophylaxis against stroke and systemic embolism in patients with atrial fibrillation or mechanical heart valves. The goal of testing is to ensure that anticoagulant levels are appropriate. Over a certain threshold, there is a risk of bleeding, while below it, there is the danger of clotting.
While warfarin toxicity can result in life-threatening risk of bleeding, inappropriate warfarin dose reduction can lead to inadequate protection from a stroke or systemic embolism.
Lab-based testing entails the patient travelling to a GP, or having a caregiver come to take blood at the patient’s home, and doing this regularly. However, even a one-day TAT for the lab test can be a major problem in terms of warfarin dosage. The utility of POCT here seems clear. The GP can know the results and adjust the medication dosage immediately. In addition, POCTs can enable certain categories of patient to self-test and manage warfarin therapy.
Lab tests as gold standard
However, POCT tests can vary significantly from laboratory analysers. In the case of warfarin monitoring, this happens as INR values rise. Correction factors are also typically device- and institution-specific. They cannot be uniformly applied across institutions. Many clinicians therefore require POCT INRs which are greater than 5.0 to be confirmed with a venipuncture sample and a lab test.
Lab tests therefore remain a gold standard. Instrumentation in a laboratory provides robust analytics during a test, and includes a host of quality controls, from test strengths and timings to testing accuracy. These are incorporated into a laboratory information system (LIS) and stored in a patient case file. POCT simply cannot provide such a depth of information.
Gaps being closed
In brief, both POCT and laboratory testing have pluses and minuses. POCT provides definite advantages and reduce risk in some situations.
However, laboratory testing is more advanced, more closely follows scientific process and is fully integrated with the kinds of technical redundancies necessary to ensure greater accuracy and validation of records.
Nevertheless, gaps between the two are being closed, especially through software technology.
Some hospitals now have dedicated satellite labs in emergency rooms and outpatient facilities equipped with POCT.
[1] https://www.ncbi.nlm.nih.gov/pubmed/7859247
[2] Bailey TM, Topham TM, Wantz S, et al. Laboratory process improvement through point-of-care testing. Jt Comm J Qual Improv 1997;23(7):362–80
April 2024
Beukenlaan 137
5616 VD Eindhoven
The Netherlands
+31 85064 55 82
info@interhospi.com
PanGlobal Media IS not responsible for any error or omission that might occur in the electronic display of product or company data.