Archive for month: August, 2020

Over the past decade, resuscitation has become one of the fastest growing areas in emergency medical care. The drivers for growth include portable, remote monitoring equipment as well as real time video-consultation. The focus of attention is on cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC), and includes all responses to sudden life-threatening events impacting on the cardiovascular and respiratory system.

Local practices continue to drive growth of best practice in resuscitation. However, there is also substantial cooperation at the global level. The International Liaison Committee on Resuscitation (ILCOR) was founded in 1993 and currently includes representatives from the American Heart Association, the Heart and Stroke Foundation of Canada, the European Resuscitation Council, the Australian and New Zealand Committee on Resuscitation, the Resuscitation Council of Asia, the Resuscitation Council of Southern Africa and the InterAmerican Heart Foundation.
ILCOR members seek to both optimize and minimize international differences in resuscitation practices, but also leave space for geographic, economic, and other real-world differences in practice and the availability of medical devices and drugs.

In 1999, the American Heart Association (AHA) hosted the first ILCOR conference to evaluate best practices and chart resuscitation guidelines. The ILCOR recommendations, formally known as International Consensus on CPR and ECC Science With Treatment Recommendations (CoSTR), were published in 2000. Over the years, ILCOR task forces have evaluated and published CoSTR recommendations in 5-year cycles.
The most recent ILCOR Consensus Conference was held in Dallas in February 2015, and attended by over 230 participants from some 40 countries. Almost two-thirds of participants came from outside the US – giving weight to ILCOR’s position as a global group. The Conference focused, as before, on CPR and ECC, but also covered first aid topics.

One good recent example of the pace of evolution in resuscitation practices is ILCOR’s observation that five years (the task force recommendation cycle) was far too long a period to inform healthcare professionals of therapeutic advances in the field. As a result, it plans to systematically review new science and publish interim advisories on treatment guidelines. The aim is to give resuscitation practitioners access to providing state-of-the-art patient care.

ILCOR’s 2015 CoSTR consensus statements summarize the results of task forces in several areas:
BLS or basic life support (covers quality of CPR and the use of an automated external defibrillator), ALS or advanced life support (post-cardiac arrest care), ACS or acute coronary syndromes, along with education, implementation and teams (EIT), and, for the first time, first aid.
Although dedicated specific task forces cover pediatric BLS and ALS as well as neonatal resuscitation, this review of the 2015 ILCOR guidelines is restricted to adults.

ILCOR task forces perform detailed systematic reviews, evaluate evidence and make recommendations. Task forces identify and prioritize questions using the PICO (population, intervention, comparator, outcome) format, accompanied by a call for public comments. This is followed by a search (with detailed inclusion/exclusion and screening) of relevant articles in three major online databases (PubMed, Embase and the Cochrane Library).

The quality of evidence is tabulated as high, moderate, low, or very low, based on five core domains of risk of bias, inconsistency, indirectness, imprecision, and publication bias (and occasionally other considerations). Together, they follow the so-called GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology for drafting guidelines.
The final wording ranges from ‘we suggest…’ for weak recommendations to ‘we recommend…’ for the strong ones… .’

One of ILCOR’s major goals is continuously-updated and high-quality research into CPR and ECC. An online platform known as SEERS (Scientific Evaluation and Evidence Review System) guides task forces and their individual reviewers, as well as public comments and suggestions. (https://volunteer.heart.org/apps/pico/Pages/default.aspx).
On the other hand, ILCOR also avoids giving attention to areas where there is little development in technology or evidence on practices.

Developments in resuscitation (2010-2015)
The 2015 CoSTR notes that post-OHCA (out-of-hospital cardiac arrest) survival rates are rising, especially when the first monitored rhythm is shockable’ – that is, associated with ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT). However, survival rates from non-shockable rhythms are also improving. These developments directly correlate with an increased emphasis on improving basic life support (BLS) and advanced life support (ALS).
Given below is a summary of evidence-based recommendations by ILCOR task forces, covering developments since 2010.

Basic life support
EMS dispatchers play the critical role in identifying cardiac arrest, providing CPR instructions to the caller, and activating emergency response. In drowning, it appears that submersion time is a key prognostic factor for outcomes. However, fundamental metrics of high-quality CPR remain the same, with an emphasis on compressions of adequate rate and depth, allowing full chest recoil after each compression, minimizing pauses in compressions, and avoiding excessive ventilation. It is also noted that public access programmes which provide early defibrillation can save many more lives if the programmes are carefully planned and coordinated.

Advanced life support
Post-cardiac arrest care is probably the resuscitation segment undergoing the greatest evolution since 2010, with substantial potential to improve survival from cardiac arrest.
Key recent developments in ALS include results from three major trials on mechanical CPR devices, drug therapy, and insertion of advanced airway devices. In addition, the ALS task force evaluated several studies regarding post-cardiac arrest care and the use of targeted temperature management (TTM).

. Mechanical devices
The three mechanical compression device trials enrolled over 7,500 patients. However, it yielded outcomes similar to those from manual compressions. ILCOR concludes that mechanical CPR devices should not be seen as replacements, but may play a role in conditions where high-quality manual compressions are not feasible.

. Drug therapy
The 2010 CoSTR had pointed to insufficient evidence about drug administration improving survival from cardiac arrest. In 2015, a systematic review identified large observational studies that also challenged routine use of advanced airways and the use of epinephrine for ALS. Since observational studies are known to carry a risk of bias, the findings did not result in a recommendation to change practice. However, they do indicate a need for large randomized controlled trials to assess whether epinephrine and advanced airways are helpful during CPR.

. Targeted Temperature Management
Recent developments in ALS also include greater delineation of the timing and effects of TTM and the need to take account of controlling oxygenation/ventilation and optimizing cardiovascular function. Nevertheless, one high quality TTM trial could not demonstrate an advantage to a temperature goal of either 33C or 36C, while five other trials failed to identify benefits from pre-hospital hypothermia initiation via cold intravenous fluids. Though none of the trials dispelled with the view that post-cardiac arrest patients need a care plan taking account of TTM, there is still little consensus about optimal target temperature and its duration.

Acute coronary syndromes
There are several evidence-based recommendations for ACS since 2010.

. Catheterization, ADP and UFH, troponins
Firstly, pre-hospital ST-segment elevation myocardial infarction (STEMI) activation of a catheterization laboratory treatment delays and improves outcomes.
Secondly, adenosine diphosphate (ADP) receptor antagonists, along with unfractionated heparin (UFH) can be part of a planned percutaneous coronary intervention (PCI) approach and be administered either pre-hospital or in-hospital for suspected STEMI patients. In the pre-hospital setting, enoxaparin is an alternative to UFH. This is not the case with bivalirudin, for which there is insufficient evidence.
Thirdly, the 2015 CoSTR discourages the use of troponins at zero and 2 hours as a standalone measure to exclude ACS diagnosis. Instead, it suggests that negative high-sensitivity troponin I (hs-cTnI) at zero and 2 hours may be used together with low-risk stratification or negative cardiac troponin I (cTnI) or cardiac troponin T (cTnT) measured at zero and 3-6 hours to identify patients at low risk of a major adverse high-sensitivity cardiac troponin I (hs-cTnI) cardiac event (MACE).

. PCI and STEMI
ILCOR’s 2015 CoSTR also has several comments on PCI and STEMI. Its find primary PCI to be generally preferable to fibrinolysis for STEMI reperfusion. However, such decisions must be individualized’ based on time from symptom onset, anticipated delay to PCI, relative contraindications to fibrinolysis, and other patient factors.
Patients with STEMI in the emergency department (ED) of a non-PCI-capable hospital should either be transported rapidly for primary PCI (without fibrinolysis) or be administered fibrinolysis and transported for routine angiography in the first 3-6 hours.

Education, implementation, and teams
One of the most noteworthy areas of attention by ILCOR since 2010 concerns training and continuous quality improvement.

Training cycles
ILCOR states that, although more evidence is needed, it is ‘now recognized’ that training should be more frequent and less time consuming to prevent skill degradation. On the other hand, retraining cycles of 1-2 years are inadequate to maintain competence in resuscitation skills. Though ‘optimal retraining intervals’ remain to be defined, it is clear that more frequent training may help providers likely to encounter a cardiac arrest.

Hi-Fi manikins
ILCOR also suggests replacing standard manikins with high-fidelity manikins at training centres with the infrastructure and resources to maintain the programme.

Performance and quality metrics, social media
Another challenge is that though the role of performance measurement and feedback in cardiac arrest response systems (both in-hospital and out-of-hospital) is recognized, supporting data is of low quality. Closely coupled to improvements in the performance of resuscitation teams is the need for data-driven, performance-focused debriefing.
Finally, ILCOR also notes the rapidly-growing role of social media for notifying suspected OHCA to hospitals and for sourcing bystanders with CPR skills.

First aid
The First Aid Task Force considered stroke assessment, hypoglycemia treatment in diabetics, as well as treatment of open chest wounds and severe bleeding and the identification of concussion.

. Stroke assessment
Observers consider one of the most important recommendations from the First Aid task force is to use stroke assessment systems to improve early identification of possible stroke and enable subsequent referral for definitive treatment. Specific recommendations are made on the FAST (Face, Arm, Speech, Time) tool as well as the Cincinnati Prehospital Stroke Scale, alongside an important observation, that blood glucose measurement could improve the specificity of recognition.

. Hypoglycemia
ILCOR’s 2015 CoSTR observes that first aid providers often face symptoms of hypoglycemia, and a failure to identify and treat it can lead to loss of consciousness and seizures. It recommends administration of glucose tablets for conscious individuals who can swallow, or substitute forms of dietary sugars should glucose tablets not be immediately available.

. Open chest wounds, bleeding, concussion
The 2015 CoSTR recommends that occlusive dressings or devices, or those which might become occlusive, be avoided in the case of open chest wounds in order to avoid engendering a tension pneumothorax.
Recommendations for severe bleeding include using direct pressure, hemostatic dressings and tourniquets – after formal training to ensure effective application and use.
The 2015 First Aid Task Force also recommends developing a simple validated concussion scoring system to accurately identify and manage concussion (minor traumatic brain injury or TBI), which is a condition often encountered by prehospital first-aid providers.

Liver disease is a growing problem across the world. It includes a large range of disorders, such as fatty liver disease (both alcoholic and non-alcoholic), drug-induced liver damage, primary biliary cirrhosis and hepatitis (viral and autoimmune).

Biopsy is gold standard for liver disease
Fibrosis is a relatively common consequence of chronic liver diseases, and its staging, alongside exclusion or confirmation of early compensated cirrhosis, are considered to be vital for surveillance and treatment decisions.
The gold standard for the confirmation of hepatic fibrosis is biopsy. However, biopsy of the liver has several disadvantages. First of all, it is invasive. It is also associated with rare but serious complications. Finally, it can sample only a small portion of the parenchyma (functional rather than connective tissue). This makes it vulnerable to sampling errors.

Non-invasive tests becoming norm
To overcome such constraints, a variety of non-invasive imaging and serological methodologies have been researched and developed for assessing fibrosis. Aside from staging, an ever-growing corpus of data from non-invasive liver tests is also yielding considerable insights for prognostic patient care.
Liver biopsy is now largely restricted to patients showing unexplained discordances in non-invasive testing or those where hepatologists suspect additional etiologies of the disease.
Indeed, non-invasive tests are fast becoming the norm in much of the world, outside the US, although there are several exceptions. The reasons for the lower penetration of non-invasive tests in the US are discussed later.

Ultrasound at forefront
New non-invasive methods for assessing liver fibrosis consists of ultrasound elastography, a diagnostic methodology to evaluate stiffness of tissue, magnetic resonance elastography and serologic testing.
To some of its proponents, elastography is simply a form of the centuries-old systems of diagnosing and assessing diseases via palpation, now extending beyond the scope of physical touch.
While a biopsy is invasive and carries bleeding and infection risks, elastography is seen as a way to get the data needed by clinicians to diagnose and stage liver diseases without the associated complications.

Ultrasound-based elastography is not only used as an alternative to liver biopsy for measuring fibrosis, but also to predict complications in patients with cirrhosis. Another advantage is that elastography, like other non-invasive imaging modalities, can be repeated as often as required to monitor disease progression. Due to their risks, this is simply not feasible with biopsy.

Strain elastography and shear wave elastography
The best-known commercial ultrasound-based techniques for assessing fibrosis include strain elastography and shear wave elastography (SWE). SWE is a real-time two-dimensional elastography technique which enables making quantitative estimates of tissue stiffness in kilopascals (kPa) by virtue of the shear wave speed.
Technologically, even though strain elastography predates SWE, the latter is more easily reproducible than strain elastography, and has rapidly gained interest as the preferred technique. The two are quite different, and outside the hepatology area, seem to have significant complementarities.
Broadly speaking, strain imaging is a qualitative/semi-quantitative method influenced by histotype and lesion size. The use of semi-quantitative indices does not improve performance. Neither does it reduce interoperator variability.

SWE provides accuracy, comparability
Shear wave, on the other hand, is a quantitative method which provides a more accurate and easily comparable assessment of spatial distribution of tissue stiffness.
Most practitioners see SWE as quick and easy to perform, and easily repeated to monitor liver disease progression and measure the effect of a particular treatment. An ultrasound shear wave propagates like ripples of water, as it spreads across tissue. A coherent pattern indicates that a pulse has been applied properly and that there are no artifacts (e.g. from vessels) that would provide erroneous results.
SWE systems provide variable depth of measurement. A depth of 5-6 cms may make it difficult to scan the liver in a large or obese patient, but depths of up to 8 cms are available in certain SWE systems. However, results are not reproducible at such depths, across commercial SWE vendors.

Ease of use not universally accepted
Nevertheless, not everyone agrees that the procedure is easy, especially if SWE results need to be matched against reproducible serological tests. The Society of Radiologists in Ultrasound notes the considerable training required for precision. SWE begins with the positioning of a patient in a left posterior oblique position with the arm raised. Patients need to also breathe slowly, and when asked, suspend breathing, since movement of the liver can reduce accuracy in measurement.

Liver is principal application for SWE
So far, SWE has been used to evaluate and quantify liver fibrosis/cirrhosis of multiple etiologies or with complicating co-morbidities, including chronic hepatitis, liver cancer, steatohepatitis, and biliary atresia. The two-dimensional shear wave elastographic technique offers better performance for assessing liver fibrosis as compared to conventional transient elastography, according to a May 2016 study in the Chinese publication, World Journal of Gastroenterology’.

SWE and hepatitis C
SWE practitioners see it as a tool to assist in earlier detection of conditions such as hepatitis C, and both fatty liver and alcoholic liver disease. Alongside lab studies, SWE offers a means to closely monitor the impact of treatment and assess if the liver will normalize. For many hepatologists, fighting a liver condition before Stage 4 cirrhosis provides a good chance of reversibility.
SWE can also provide information on which hepatitis C patients might benefit from viral therapy. There are numerous reports of patients who would not have been suspected of severe fibrosis or cirrhosis, based on traditional ultrasound grey scaling. At best, the latter provides indicators such as anomalies in the liver contour. However, it does not show signs of cirrhosis such as surface nodularity which are immediately apparent in elastography.

Guiding biopsies
Some clinicians have sought to use SWE to guide liver biopsies and in certain cases, avoid or postpone biopsy. As part of this process, they have addressed one of the major limitations of biopsy, namely restrictions to choice of affected areas, erroneous samples, or inadequacy in sample size enough for interpretation. SWE allows multiple sampling across the liver and generating a mean value. This reduces what in the past would have been a large number of unnecessary biopsies, and minimizes the morbidity of liver biopsy.

SWE in children
SWE has shown specific advantages in pediatric patients. Cincinnati Children’s Hospital Medical Center is gathering data on normal’ stiffness values in children, and on rates of progression, given that published data is almost wholly based on adults.
The study groups cover children with liver transplants, metabolic disorders, cystic fibrosis and those on prolonged intravenous feeding (TPN). One specific area for attention is biliary atresia, a rare but life-threatening condition where the bile ducts in an infant’s liver lack normal openings. The bile builds up and causes damage to the liver.
The pediatric data collection for SWE on newborns with jaundice or cholestasis makes ten measurements. This adds just 5 minutes to a typical ultrasound exam.
Nevertheless, pediatric SWE also has its limitations. According to Dr. Sara O’Hara, who heads the Ultrasound Department at Cincinnati Children’s Hospital, SWE can give variable results in areas such as children with non alcoholic steatohepatitis (NASH) and fatty liver disease.

Breast applications benefit from SWE-plus-strain elastography
In adults, aside from the liver, SWE is seen as a useful technique for evaluation of breast lesions and prostate imaging. In both cases, the technique seems to provide best results in combination with another elastography mode.
For instance, a literature review published in the Journal of Ultrasound’ in 2012 reported that SWE and strain elastography complement each other and overcome mutual limitations in the evaluation of breast lesions.
Clearly, when both types of elastography provide similar results, there is a greater degree of confidence – especially in terms of a near-total elimination of false negatives, which sharply cuts the need for breast biopsies which later prove unnecessary.
There are however some limitations which have been reported in measuring shear wave velocity in the stiffest of breast lesions. Here, rather than propagating through the tumour, the shear wave tends to bounce back. Nevertheless, ongoing improvements in SWE, which have been further reducing examination time and enhancing field of view, means that at some point it could be a tool for breast cancer screening.

Prostate applications benefit from SWE-plus-MR elastography
The use of SWE in prostate cancer, too, shows similar potential for benefits as with breast screening. The first factor is a reduction in biopsies, which prove to have been unnecessary post facto. Studies are under way which seek to correlate stiffness with abnormalities (as well as aggressiveness of tumours) and to assist urologists determine when patients with low-grade prostate cancer must start treatment.
As with SWE and strain elastography in the breast, best results in terms of the prostate are obtained by complementing SWE with another imaging modality – magnetic resonance (MR) elastography. Some findings reveal SWE significantly superior in detecting prostate cancer in the peripheral zone – which is where most tumours occur. However, MR seems to show greater promise in the anterior gland and transitional zone.
Again, as with the breast, the fusion of two modalities permits multiple sampling and tackles a major limitation of prostate biopsy, namely inconvenience and risk, as well as limited choice of affected areas. A few experimental procedures have also targeted fusing MR and SWE images to help guide biopsies.

Using SWE in other organs
SWE has also demonstrated considerable (if still early-stage) promise for evaluating thyroid nodules, indeterminate lymph nodes and uterine fibroids. Another area for investigating SWE include kidney transplants, in order to to avoid excessive biopsies. However, limitations to shear wave captured depth remains a technology challenge for manufacturers to address.

US remains laggard in ultrasound elastography
While most of the world’s regions (Europe, Asia and Latin America) are seeing growth in the use of ultrasound elastography (both SWE and strain), in the US neither is eligible for reimbursement, even in the largest application area – the liver. This is unlike transient elastography, although critics allege it is a blind methodology which neither directly measure fibrosis and often over-estimates it.
Currently, studies in both the US and other parts of the world are seeking to establish the clinical and economic benefits of SWE and strain elastography, including unnecessary invasive biopsies with their associated costs and complications. Eventually, the results of ongoing trials are expected to produce the data which will make ultrasound elastography eligible for reimbursement.
The most self-evident advantage of ultrasound elastography is its non-invasive nature. Unlike a biopsy, it is clearly more feasible to use SWE to screen for patients at greatest risk of chronic liver disease and in need of referral or treatment.