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Monday, February 6, 2023

Emergency medical services

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Emergency_medical_services
 
Ambulances lined up in Tallahassee, FL prior to deployment during Hurricane Irma.
 
An ambulance in Lausanne (Switzerland) marked with multiple Stars of Life (representing emergency medical services).
 
Ambulance vehicle with the emblem of the Red Cross in Nizhny Novgorod, Russia.
 
Emergency medical services prepare to airlift the victim of a car accident to hospital, in Ontario, Canada.

Emergency medical services (EMS), also known as ambulance services or paramedic services, are emergency services that provide urgent pre-hospital treatment and stabilisation for serious illness and injuries and transport to definitive care. They may also be known as a first aid squad, FAST squad, emergency squad, ambulance squad, ambulance corps, life squad or by other initialisms such as EMAS or EMARS.

In most places, the EMS can be summoned by members of the public (as well as medical facilities, other emergency services, businesses and authorities) via an emergency telephone number which puts them in contact with a control facility, which will then dispatch a suitable resource for the situation. Ambulances are the primary vehicles for delivering EMS, though some also use squad cars, motorcycles, aircraft, or boats. EMS agencies may also operate a non-emergency patient transport service, and some have rescue squads to provide technical rescue services.

As a first resort the EMS provide treatment on the scene to those in need of urgent medical care. If it is deemed necessary, they are tasked with transferring the patient to the next point of care. This is most likely an emergency department of a hospital. Historically, ambulances only transported patients to care, and this remains the case in parts of the developing world. The term "emergency medical service" was popularised when these services began to emphasise diagnosis and treatment at the scene. In some countries, a substantial portion of EMS calls do not result in a patient being taken to hospital.

Training and qualification levels for members and employees of emergency medical services vary widely throughout the world. In some systems, members may be present who are qualified only to drive ambulances, with no medical training. In contrast, most systems have personnel who retain at least basic first aid certifications, such as basic life support (BLS). In English-speaking countries, they are known as emergency medical technicians (EMTs) and paramedics, with the latter having additional training such as advanced life support (ALS) skills. Physicians and nurses also provide pre-hospital care to varying degrees in different countries.

History

Precursors

Emergency care in the field has been rendered in different forms since the beginning of recorded history. The New Testament contains the parable of the Good Samaritan, in which a man who has been beaten is cared for by a passing Samaritan. Luke 10:34 (NIV) – "He went to him and bandaged his wounds, pouring on oil and wine. Then he put the man on his own donkey, took him to an inn and took care of him." During the Middle Ages, the Knights Hospitaller were known for rendering assistance to wounded soldiers in the battlefield.

A drawing of one of Larrey's ambulances volantes.

The first use of the ambulance as a specialized vehicle, in battle came about with the ambulances volantes designed by Dominique Jean Larrey (1766–1842), Napoleon Bonaparte's chief surgeon. Larrey was present at the battle of Spires, between the French and Prussians, and was distressed by the fact that wounded soldiers were not picked up by the numerous ambulances (which Napoleon required to be stationed two and half miles back from the scene of battle) until after hostilities had ceased, and set about developing a new ambulance system. Having decided against using the Norman system of horse litters, he settled on two- or four-wheeled horse-drawn wagons, which were used to transport fallen soldiers from the (active) battlefield after they had received early treatment in the field. Larrey's projects for 'flying ambulances' were first approved by the Committee of Public Safety in 1794. Larrey subsequently entered Napoleon's service during the Italian campaigns in 1796, where his ambulances were used for the first time at Udine, Padua and Milan, and he adapted his ambulances to the conditions, even developing a litter which could be carried by a camel for a campaign in Egypt.

Early civilian ambulances

A major advance was made (which in future years would come to shape policy on hospitals and ambulances) with the introduction of a transport carriage for cholera patients in London during 1832. The statement on the carriage, as printed in The Times, said "The curative process commences the instant the patient is put in to the carriage; time is saved which can be given to the care of the patient; the patient may be driven to the hospital so speedily that the hospitals may be less numerous and located at greater distances from each other". This tenet of ambulances providing instant care, allowing hospitals to be spaced further apart, displays itself in modern emergency medical planning.

A horse-drawn Bellevue Hospital ambulance in New York City, 1895.

The first known hospital-based ambulance service operated out of Commercial Hospital, Cincinnati, Ohio (now the Cincinnati General) by 1865. This was soon followed by other services, notably the New York service provided out of Bellevue Hospital which started in 1869 with ambulances carrying medical equipment, such as splints, a stomach pump, morphine, and brandy, reflecting contemporary medicine.

Another early ambulance service was founded by Jaromir V. Mundy, Count J. N. Wilczek, and Eduard Lamezan-Salins in Vienna after the disastrous fire at the Vienna Ringtheater in 1881. Named the "Vienna Voluntary Rescue Society," it served as a model for similar societies worldwide.

In June 1887 the St John Ambulance Brigade was established to provide first aid and ambulance services at public events in London. It was modelled on a military-style command and discipline structure.

Motorization

A Royal Navy ambulance during World War I.

Also in the late 19th century, the automobile was being developed, and in addition to horse-drawn models, early 20th century ambulances were powered by steam, gasoline, and electricity, reflecting the competing automotive technologies then in existence. However, the first motorized ambulance was brought into service in the last year of the 19th century, with the Michael Reese Hospital, Chicago, taking delivery of the first automobile ambulance, donated by 500 prominent local businessmen, in February 1899. This was followed in 1900 by New York City, who extolled its virtues of greater speed, more safety for the patient, faster stopping and a smoother ride. These first two automobile ambulances were electrically powered with 2 hp motors on the rear axle.

During World War I, further advances were made in providing care before and during transport; traction splints were introduced during the war and were found to have a positive effect on the morbidity and mortality of patients with leg fractures. Two-way radios became available shortly after World War I, enabling for more efficient radio dispatch of ambulances in some areas. Prior to World War II, there were some areas where a modern ambulance carried advanced medical equipment, was staffed by a physician, and was dispatched by radio. In many locations, however, ambulances were hearses, the only available vehicle that could carry a recumbent patient, and were thus frequently run by funeral homes. These vehicles, which could serve either purpose, were known as combination cars.

Prior to World War II, hospitals provided ambulance service in many large cities. With the severe manpower shortages imposed by the war effort, it became difficult for many hospitals to maintain their ambulance operations. City governments in many cases turned ambulance services over to the police or fire department. No laws required minimal training for ambulance personnel and no training programs existed beyond basic first aid. In many fire departments, assignment to ambulance duty became an unofficial form of punishment.

Rise of modern EMS

A 1973 Cadillac Miller-Meteor ambulance. Note the raised roof, with more room for the attendants and patients

Advances in the 1960s, especially the development of CPR and defibrillation as the standard form of care for out-of-hospital cardiac arrest, along with new pharmaceuticals, led to changes in the tasks of the ambulances. In Belfast, Northern Ireland the first experimental mobile coronary care ambulance successfully resuscitated patients using these technologies. Freedom House Ambulance Service was the first civilian emergency medical service in the United States to be staffed by paramedics, most of which were black.

One well-known report in the US during that time was Accidental Death and Disability: The Neglected Disease of Modern Society, also known as The White Paper. The report concluded that ambulance services in the US varied widely in quality and were often unregulated and unsatisfactory.[25] These studies placed pressure on governments to improve emergency care in general, including the care provided by ambulance services. The government reports resulted in the creation of standards in ambulance construction concerning the internal height of the patient care area (to allow for an attendant to continue to care for the patient during transport), and the equipment (and thus weight) that an ambulance had to carry, and several other factors.

In 1971 a progress report was published at the annual meeting, by the then president of American Association of Trauma, Sawnie R. Gaston M.D. Dr. Gaston reported the study was a "superb white paper" that "jolted and wakened the entire structure of organized medicine." This report is created as a "prime mover" and made the "single greatest contribution of its kind to the improvement of emergency medical services". Since this time a concerted effort has been undertaken to improve emergency medical care in the pre-hospital setting. Such advancements included Dr. R Adams Cowley creating the country's first statewide EMS program, in Maryland.

The developments were paralleled in other countries. In the United Kingdom, a 1973 law merged the municipal ambulance services into larger agencies and set national standards. In France, the first official SAMU agencies were founded in the 1970s.

Organization

Depending on country, area within country, or clinical need, emergency medical services may be provided by one or more different types of organization. This variation may lead to large differences in levels of care and expected scope of practice. Some countries closely regulate the industry (and may require anyone working on an ambulance to be qualified to a set level), whereas others allow quite wide differences between types of operator.

Government ambulance service

A government-owned ambulance in Kyiv, Ukraine

Operating separately from (although alongside) the fire and police services of the area, these ambulances are funded by local, provincial or national governments. In some countries, these only tend to be found in big cities, whereas in countries such as the United Kingdom, almost all emergency ambulances are part of a national health system.

In the United States, ambulance services provided by a local government are often referred to as "third service" EMS (the fire department, police department, and separate EMS forming an emergency services trio) by the employees of said service, as well as other city officials and residents. The most notable examples of this model in the United States are Pittsburgh Bureau of Emergency Medical Services (PEMS), Boston EMS, New Orleans Emergency Medical Services, Austin-Travis County Emergency Medical Services, Cleveland EMS, Wake County Emergency Medical Services and Honolulu EMS Archived 3 April 2022 at the Wayback Machine. Government ambulance services also have to take civil service exams just like government fire departments and police. In the United States, certain federal government agencies employ emergency medical technicians at the basic and advanced life support levels, such as the National Park Service and the Federal Bureau of Prisons.

Fire- or police-linked service

In countries such as the United States, Japan, France, South Korea and parts of India, ambulances can be operated by the local fire or police services. Fire-based EMS is the most common model in the United States, where nearly all urban fire departments provide EMS and a majority of emergency transport ambulance services in large cities are part of fire departments. It is somewhat rare for a police department in the United States to provide EMS or ambulance services, although many police officers have basic medical training. One notable example is New Orleans Emergency Medical Services, which was formed as a hospital-based service, was operated by the New Orleans Police Department from 1947 to 1985, and is currently operated by the New Orleans Health Department and the New Orleans Office of Homeland Security and Emergency Preparedness, separate from the New Orleans Fire Department.

Charity ambulance service

A volunteer ambulance crew in Modena, Italy

Charities or non-profit companies operate some emergency medical services. They are primarily staffed by volunteers, though some have paid personnel. These may be linked to a volunteer fire service, and some volunteers may provide both services. Some ambulance charities specialize in providing cover at public gatherings and events (e.g. sporting events), while others provide care to the wider community.

The International Red Cross and Red Crescent Movement is the largest charity in the world that provides emergency medicine. (in some countries, it operates as a private ambulance service). Other organisations include St John Ambulance, the Order of Malta Ambulance Corps and Hatzalah, as well as small local volunteer agencies. In the United States, volunteer ambulances are rarer, but can still be seen in both metropolitan and rural areas (e.g. Hatzalah). Charities such as BASICS Scotland, specialise in facilitating training medical professionals to volunteer to assist the statutory ambulance services in the care of patients, through their attendance at those with serious illnesses or injuries.

A few charities provide ambulances for taking patients on trips or vacations away from hospitals, hospices or care homes where they are in long-term care. Examples include the UK's Jumbulance project.

Private ambulance service

Some ambulances are operated by commercial companies with paid employees, usually on a contract to the local or national government, Hospital Networks, Health Care Facilities and Insurance Companies.

In the USA private ambulance companies provide 911 emergency services in large cities as well as most rural areas by contracting with local governments. In areas that the local County or City provide their own 911 service, private companies provide discharges and transfers from hospitals and to/from other health related facilities and homes. In most areas private companies are part of the local government Emergency Disaster plan, and are relied upon heavily for the overall EMS response, treatment and recovery.

In some areas, private companies may provide only the patient transport elements of ambulance care (i.e. non-urgent), but in some places, they are contracted to provide emergency care, or to form a 'second tier' response, where they only respond to emergencies when all of the full-time emergency ambulance crews are busy. This may mean that a government or other service provide the 'emergency' cover, whilst a private firm may be charged with 'minor injuries' such as cuts, bruises or even helping the mobility-impaired if they have for example fallen and simply need help to get up again, but do not need treatment. This system has the benefit of keeping emergency crews available at all times for genuine emergencies. These organisations may also provide services known as 'Stand-by' cover at industrial sites or at special events. In Latin America, private ambulance companies are often the only readily-available EMS service

Combined emergency service

These are full service emergency service agencies, which may be found in places such as airports or large colleges and universities. Their key feature is that all personnel are trained not only in ambulance (EMT) care, but as a firefighter and a peace officer (police function). They may be found in smaller towns and cities, where demand or budget is too low to support separate services. This multi-functionality allows to make the most of limited resource or budget, but having a single team respond to any emergency.

Hospital-based service

Hospitals may provide their own ambulance service as a service to the community, or where ambulance care is unreliable or chargeable. Their use would be dependent on using the services of the providing hospital.

Internal ambulances

Many large factories and other industrial centres, such as chemical plants, oil refineries, breweries and distilleries have ambulance services provided by employers as a means of protecting their interests and the welfare of their staff. These are often used as first response vehicles in the event of a fire or explosion.

Purpose

Six points on the Star of Life

Emergency medical services exists to fulfill the basic principles of first aid, which are to Preserve Life, Prevent Further Injury, and Promote Recovery. This common theme in medicine is demonstrated by the "star of life". The Star of Life shown here, where each of the 'arms' to the star represent one of the six points, are used to represent the six stages of high quality pre-hospital care, which are:

  1. Early detection – members of the public, or another agency, find the incident and understand the problem
  2. Early reporting – the first persons on scene make a call to the emergency medical services (911) and provide details to enable a response to be mounted
  3. Early response – the first professional (EMS) rescuers are dispatched and arrive on scene as quickly as possible, enabling care to begin
  4. Good on-scene/field care – the emergency medical service provides appropriate and timely interventions to treat the patient at the scene of the incident without doing further harm.
  5. Care in transit -– the emergency medical service load the patient in to suitable transport and continue to provide appropriate medical care throughout the journey
  6. Transfer to definitive care – the patient is handed over to an appropriate care setting, such as the emergency department at a hospital, in to the care of physicians

Strategies for delivering care

Training for EMS in Estonia.

Although a variety of differing philosophical approaches are used in the provision of EMS care around the world, they can generally be placed into one of two categories; one physician-led and the other led by pre-hospital allied health staff such as emergency medical technicians or paramedics. These models are commonly referred to as the Franco-German model and Anglo-American model.

Studies have been inconclusive as to whether one model delivers better results than the other. A 2010 study in the Oman Medical Journal suggested that rapid transport was a better strategy for trauma cases, while stabilization at the scene was a better strategy for cardiac arrests.

Levels of care

Bags of medical supplies and defibrillators at the York Region EMS Logistics Headquarters in Ontario, Canada

Many systems have tiers of response for medical emergencies. For example, a common arrangement in the United States is that fire engines or volunteers are sent to provide a rapid initial response to a medical emergency, while an ambulance is sent to provide advanced treatment and transport the patient. In France, fire service and private company ambulances provide basic care, while hospital-based ambulances with physicians on board provide advanced care. In many countries, an air ambulance provides a higher level of care than a regular ambulance.

Examples of level of care include:

  • First aid consists of basic skills that are commonly taught to members of the public, such as cardiopulmonary resuscitation, bandaging wounds and saving someone from choking.
  • Basic Life Support (BLS) is often the lowest level of training that can be held by those who treat patients on an ambulance. Commonly, it includes administering oxygen therapy, some drugs and a few invasive treatments. BLS personnel may either operate a BLS ambulance on their own, or assist a higher qualified crewmate on an ALS ambulance. In English-speaking countries, BLS ambulance crew are known as emergency medical technicians or emergency care assistants.
  • Intermediate Life Support (ILS), also known as Limited Advanced Life Support (LALS), is positioned between BLS and ALS but is less common than both. It is commonly a BLS provider with a moderately expanded skill set, but where it is present it usually replaces BLS.
  • Advanced Life Support (ALS) has a considerably expanded range of skills such as intravenous therapy, cricothyrotomy and interpreting an electrocardiogram. The scope of this higher tier response varies considerably by country. Paramedics commonly provide ALS, but some countries require it to be a higher level of care and instead employ physicians in this role. Additionally Advanced Life Support includes administering therapeutic doses of electrical shock to those who are in cardiac arrest or using drugs to stimulate the heart, Airway therapy, and so on and so forth. Most ambulances are equipped with advanced Life Support equipment and have paramedics on board. While some fire departments have ambulances, first aid and squads utilize ambulances for emergency medical services.
  • Critical Care Transport (CCT), also known as medical retrieval or rendez vous MICU protocol in some countries (Australia, NZ, Great Britain, and Francophone Canada) refers to the critical care transport of patients between hospitals (as opposed to pre-hospital). Such services are a key element in regionalized systems of hospital care where intensive care services are centralized to a few specialist hospitals. An example of this is the Emergency Medical Retrieval Service in Scotland. This level of care is likely to involve traditional healthcare professionals (in addition to or instead of critical care-trained paramedics), meaning nurses and/or physicians working in the pre-hospital setting and even on ambulances.

Transport-only

The most basic emergency medical services are provided as a transport operation only, simply to take patients from their location to the nearest medical treatment. This was historically the case in all countries. It remains the case in much of the developing world, where operators as diverse as taxi drivers and undertakers may transport people to hospital.

Transport-centered EMS

Ambulances parked outside a local emergency room.

The Anglo-American model is also known as "load and go" or "scoop and run". In this model, ambulances are staffed by paramedics and/or emergency medical technicians. They have specialized medical training, but not to the same level as a physician. In this model it is rare to find a physician actually working routinely in ambulances, although they may be deployed to major or complex cases. The physicians who work in EMS provide oversight for the work of the ambulance crews. This may include off-line medical control, where they devise protocols or 'standing orders' (procedures for treatment). This may also include on-line medical control, in which the physician is contacted to provide advice and authorization for various medical interventions.

In some cases, such as in the UK, South Africa and Australia, a paramedic may be an autonomous health care professional, and does not require the permission of a physician to administer interventions or medications from an agreed list, and can perform roles such as suturing or prescribing medication to the patient. Recently "Telemedicine" has been making an appearance in ambulances. Similar to online medical control, this practice allows paramedics to remotely transmit data such as vital signs and 12 and 15 lead ECGs to the hospital from the field. This allows the emergency department to prepare to treat patients prior to their arrival. This is allowing lower level providers (Such as EMT-B) in the United States to utilize these advanced technologies and have the doctor interpret them, thus bringing rapid identification of rhythms to areas where paramedics are stretched thin. While most insurance companies only reimburse EMS providers for transporting patients to 911 receiving facilities (e.g. Emergency Departments),the Center to Medicare and Medicaid Services is in the process of evaluating a payment model to enable reimbursement for patients evaluated and treated on-scene.

Major trauma

The essential decision in prehospital care is whether the patient should be immediately taken to the hospital, or advanced care resources are taken to the patient where they lie. The "scoop and run" approach is exemplified by the MEDEVAC aeromedical evacuation helicopter, whereas the "stay and play" is exemplified by the French and Belgian SMUR emergency mobile resuscitation unit or the German "Notarzt"-System (preclinical emergency physician).

The strategy developed for prehospital trauma care in North America is based on the Golden Hour theory, i.e., that a trauma victim's best chance for survival is in an operating room, with the goal of having the patient in surgery within an hour of the traumatic event. This appears to be true in cases of internal bleeding, especially penetrating trauma such as gunshot or stab wounds. Thus, minimal time is spent providing prehospital care (spine immobilization; "ABCs", i.e. ensure airway, breathing and circulation; external bleeding control; endotracheal intubation) and the victim is transported as fast as possible to a trauma centre.

The aim in "Scoop and Run" treatment is generally to transport the patient within ten minutes of arrival, hence the birth of the phrase, "the platinum ten minutes" (in addition to the "golden hour"), now commonly used in EMT training programs. The "Scoop and Run" is a method developed to deal with trauma, rather than strictly medical situations (e.g. cardiac or respiratory emergencies), however, this may be changing. Increasingly, research into the management of S-T segment elevation myocardial infarctions (STEMI) occurring outside of the hospital, or even inside community hospitals without their own PCI labs, suggests that time to treatment is a clinically significant factor in heart attacks, and that trauma patients may not be the only patients for whom 'load and go' is clinically appropriate. In such conditions, the gold standard is the door to balloon time. The longer the time interval, the greater the damage to the myocardium, and the poorer the long-term prognosis for the patient. Current research in Canada has suggested that door to balloon times are significantly lower when appropriate patients are identified by paramedics in the field, instead of the emergency room, and then transported directly to a waiting PCI lab. The STEMI program has reduced STEMI deaths in the Ottawa region by 50 per cent. In a related program in Toronto, EMS has begun to use a procedure of 'rescuing' STEMI patients from the Emergency Rooms of hospitals without PCI labs, and transporting them, on an emergency basis, to waiting PCI labs in other hospitals.

Physician-led EMS

Ambulance in the Czech Republic

Physician-led EMS is also known as the Franco-German model, "stay and play", "stay and stabilize" or "delay and treat". In a physician-led system, doctors respond directly to all major emergencies requiring more than simple first aid. The physicians will attempt to treat casualties at the scene and will only transport them to hospital if it is deemed necessary. If patients are transported to hospital, they are more likely to go straight to a ward rather than to an emergency department. Countries that use this model include Austria, France, Belgium, Luxembourg, Italy, Spain, Brazil and Chile.

In some cases in this model, such as France, there is no direct equivalent to a paramedic. Physicians and (in some cases) nurses provide all medical interventions for the patient. Other ambulance personnel are not non-medically trained and only provide driving and heavy lifting. In other applications of this model, as in Germany, a paramedic equivalent does exist, but is an assistant to the physician with a restricted scope of practice. They are only permitted to perform Advanced Life Support (ALS) procedures if authorized by the physician, or in cases of immediate life-threatening conditions. Ambulances in this model tend to be better equipped with more advanced medical devices, in essence, bringing the emergency department to the patient. High-speed transport to hospitals is considered, in most cases, to be unnecessarily unsafe, and the preference is to remain and provide definitive care to the patient until they are medically stable, and then accomplish transport. In this model, the physician and nurse may actually staff an ambulance along with a driver, or may staff a rapid response vehicle instead of an ambulance, providing medical support to multiple ambulances.

Personnel

EMT staff at an emergency call in New York City
 
 
A patient arriving at hospital

Ambulance personnel are generally professionals and in some countries their use is controlled through training and registration. While these job titles are protected by legislation in some countries, this protection is by no means universal, and anyone might, for example, call themselves an 'EMT' or a 'paramedic', regardless of their training, or the lack of it. In some jurisdictions, both technicians and paramedics may be further defined by the environment in which they operate, including such designations as 'Wilderness', 'Tactical', and so on.

A unique aspect of EMS is that there are two hierarchies of authority, as the chain of command is separate to medical authority.

Basic life support (BLS)

First responder

Certified first responders may be sent to provide first aid, sometimes to an advanced level. Their duties include the provision of immediate life-saving care in the event of a medical emergency; commonly advanced first aid, oxygen administration, cardio-pulmonary resuscitation (CPR), and automated external defibrillator (AED) usage. The first responder training is considered a bare minimum for emergency service workers who may be sent out in response to an emergency call. First responders are commonly dispatched by the ambulance service to arrive quickly and stabilize the patient before the ambulance arrives, and to then assist the ambulance crew.

Some EMS agencies have set up volunteer schemes, who can be dispatched to a medical emergency before the ambulance arrives. Examples of this include Community First Responder schemes run by ambulance services the UK and similar volunteer schemes operated by the fire services in France. In some countries such as the US, there may be autonomous groups of volunteer responders such as rescue squads. Police officers and firefighters who are on duty for another emergency service may also be deployed in this role, though some firefighters are trained to a more advanced medical level.

Besides first responders who are deployed to an emergency, there are others who may be stationed at public events. The International Red Cross and Red Crescent Movement and St John Ambulance both provide first aiders in these roles.

Driver

Some agencies separate the 'driver' and 'attendant' functions, employing ambulance driving staff with no medical qualification (or just a first aid and CPR certificates), whose job is to drive ambulances. While this approach persists in some countries, such as India, it is generally becoming increasingly rare. Ambulance drivers may be trained in radio communications, ambulance operations and emergency response driving skills.

Non-emergency driver/attendant

Many countries employ ambulance staff who only carry out non-emergency patient transport duties (which can include stretcher or wheelchair cases). Dependent on the provider (and resources available), they may be trained in first aid or extended skills such as use of an AED, oxygen therapy, pain relief and other live-saving or palliative skills. In some services, they may also provide emergency cover when other units are not available, or when accompanied by a fully qualified technician or paramedic. The role is known as an Ambulance Care Assistant in the United Kingdom.

Emergency medical technician

EMTs loading a patient into an ambulance

Emergency medical technicians, also known as Ambulance Technicians in the UK and EMT in the United States. In the United States, EMT is usually made up of 3 levels. EMT-B, EMT-I (EMT-A in some states) and EMT-Paramedic. The National Registry of EMT New Educational Standards for EMS renamed the provider levels as follows: Emergency Medical Responder (EMR), Emergency Medical Technician (EMT), Advanced EMT (AEMT), and Paramedic. EMTs are usually able to perform a wide range of emergency care skills, such as automated defibrillation, care of spinal injuries and oxygen therapy. In few jurisdictions, some EMTs are able to perform duties as IV and IO cannulation, administration of a limited number of drugs (including but not limited to Epinephrine, Narcan, Oxygen, Aspirin, Nitroglycerin - dependent on country, state, and medical direction), more advanced airway procedures, CPAP, and limited cardiac monitoring. Most advanced procedures and skills are not within the national scope of practice for an EMT. As such most states require additional training and certifications to perform above the national curriculum standards. In the US, an EMT certification requires intense courses and training in field skills. A certification expires after two years and holds a requirement of taking 48 CEUs (continuing education credits). 24 of these credits must be in refresher courses while the other 24 can be taken in a variety ways such as emergency driving training, pediatric, geriatric, or bariatric care, specific traumas, etc.

Emergency medical dispatcher

An emergency medical dispatcher is also called an EMD. An increasingly common addition to the EMS system is the use of highly trained dispatch personnel who can provide "pre-arrival" instructions to callers reporting medical emergencies. They use carefully structured questioning techniques and provide scripted instructions to allow callers or bystanders to begin definitive care for such critical problems as airway obstructions, bleeding, childbirth, and cardiac arrest. Even with a fast response time by a first responder measured in minutes, some medical emergencies evolve in seconds. Such a system provides, in essence, a "zero response time," and can have an enormous impact on positive patient outcomes.

Advanced life support (ALS)

Paramedic

A girl treated by a paramedic

A paramedic has a high level of pre-hospital medical training and usually involves key skills not performed by technicians, often including cannulation (and with it the ability to use a range of drugs to relieve pain, correct cardiac problems, and perform endotracheal intubation), cardiac monitoring, ultrasound, intubation, pericardiocentesis, cardioversion, thoracostomy, and other skills such as performing a surgical cricothyrotomy. The most important function of the paramedic is to identify and treat any life-threatening conditions and then to assess the patient carefully for other complaints or findings that may require emergency treatment. In many countries, this is a protected title, and use of it without the relevant qualification may result in criminal prosecution. In the United States, paramedics represent the highest licensure level of prehospital emergency care. In addition, several certifications exist for Paramedics such as Wilderness ALS Care, Flight Paramedic Certification (FP-C), and Critical Care Emergency Medical Transport Program certification.

Critical care paramedic

A Toronto Critical Care ambulance

A critical care paramedic, also known as an advanced practice paramedic or specialist paramedic, is a paramedic with additional training to deal with critically ill patients. Critical care paramedics often work on air ambulances, which are more likely to be dispatched to emergencies requiring advanced care skills. They may also work on land ambulances. The training, permitted skills, and certification requirements vary from one jurisdiction to the next. It also varies to whether they are trained externally by a university or professional body or 'in house' by their EMS agency.

These providers have a vast array of and medications to handle complex medical and trauma patients. Examples of medication are dopamine, dobutamine, propofol, blood and blood products to name just a few. Some examples of skills include, but not limited to, life support systems normally restricted to the ICU or critical care hospital setting such as mechanical ventilators, Intra-aortic balloon pump (IABP) and external pacemaker monitoring. Depending on the service medical direction, these providers are trained on placement and use of UVCs (Umbilical Venous Catheter), UACs (Umbilical Arterial Catheter), surgical airways, central lines, arterial lines and chest tubes.

Paramedic practitioner / emergency care practitioner

In the United Kingdom and South Africa, some serving paramedics receive additional university education to become practitioners in their own right, which gives them absolute responsibility for their clinical judgement, including the ability to autonomously prescribe medications, including drugs usually reserved for doctors, such as courses of antibiotics. An emergency care practitioner is a position that is designed to bridge the link between ambulance care and the care of a general practitioner. ECPs are university graduates in Emergency Medical Care or qualified paramedics who have undergone further training, and are authorized to perform specialized techniques. Additionally some may prescribe medicines (from a limited list) for longer-term care, such as antibiotics. With respect to a Primary Health Care setting, they are also educated in a range of Diagnostic techniques.

Traditional healthcare professions

Registered nurses

The use of registered nurses (RNs) in the pre-hospital setting is common in many countries in absence of paramedics. In some regions of the world nurses are the primary healthcare worker that provides emergency medical services. In European countries such as France or Italy, also use nurses as a means of providing ALS services. These nurses may work under the direct supervision of a physician, or, in rarer cases, independently. In some places in Europe, notably Norway, paramedics do exist, but the role of the 'ambulance nurse' continues to be developed, as it is felt that nurses may bring unique skills to some situations encountered by ambulance crews.

In North America, and to a lesser extent elsewhere in the English-speaking world, some jurisdictions use specially trained nurses for medical transport work. These are mostly air-medical personnel or critical care transport providers, often working in conjunction with a technician, paramedic or physician on emergency interfacility transports. In the United States, the most common uses of ambulance-based registered nurses is in the Critical Care/Mobile Intensive Care transport, and in Aeromedical EMS. Such nurses are normally required by their employers (in the US) to seek additional certifications beyond the primary nursing licensure. Four individual states have an Intensive Care or Prehospital Nurse licensure. Many states allow registered nurses to also become registered paramedics according to their role in the emergency medical services team. In Estonia 60% of ambulance teams are led by nurse. Ambulance nurses can do almost all emergency procedures and administer medicines pre-hospital such as physicians in Estonia. In the Netherlands, all ambulances are staffed by a registered nurse with additional training in emergency nursing, anaesthesia or critical care, and a driver-EMT. In Sweden, since 2005, all emergency ambulances should be staffed by at least one registered nurse since only nurses are allowed to administer drugs. And all Advanced Life Support Ambulances are staffed at least by a registered nurse in Spain. In France, since 1986, fire department-based rescue ambulances have had the option of providing resuscitation service (reanimation) using specially trained nurses, operating on protocols, while SAMU-SMUR units are staffed by physicians and nurses

Physician

In countries with a physician-led EMS model, such as France, Italy, the German-speaking countries (Germany, Switzerland, Austria), and Spain, physicians respond to all cases that require more than basic first aid. In some versions of this model (such as France, Italy, and Spain), there is no direct equivalent to a paramedic, as ALS is performed by physicians. In the German-speaking countries, paramedics are assistants to ambulance physicians (called Notarzt). In these countries, if a physician is present, paramedics require permission from the physician to administer treatments such as defibrillation and drugs. If there is no physician on scene and a life-threatening condition is present, they may administer treatments that follow the physician's instructions.

In countries where EMS is led by paramedics, the ambulance service may still employ physicians. They may serve on specialist response vehicles, such as the air ambulances in the UK. They may also provide advice and devise protocols for treatment, with a medical director acting as the most senior medical adviser to the ambulance service. In the United States, EMS became an officially recognized subspecialty by the American Board of Emergency Medicine in 2010, and the first examinations were held in 2013. Many states now recommend EMS board certifiction for newly hired Medical Directors of EMS agencies.

Specialist EMS

Air ambulance

A Canadian STARS helicopter ambulance. Air ambulances often have staff who are specially trained for dealing with major trauma cases.
 

Air ambulances often complement a land ambulance service. In some remote areas, they may even form the primary ambulance service. Like many innovations in EMS, medical aircraft were first used in the military. One of the first recorded aircraft rescues of a casualty was in 1917 in Turkey, when a soldier in the Camel Corps who had been shot in the ankle was flown to hospital in a de Havilland DH9. In 1928, the first civilian air medical service was founded in Australia to provide healthcare to people living in remote parts of the Outback. This service became the Royal Flying Doctor Service. The use of helicopters was pioneered in the Korean War, when time to reach a medical facility was reduced from 8 hours to 3 hours in World War II, and again to 2 hours by the Vietnam War.

Aircraft can travel faster and operate in a wider coverage area than a land ambulance. They have a particular advantage for major trauma injuries. The well-established theory of the golden hour suggests that major trauma patients should be transported as quickly as possible to a specialist trauma center. Therefore, medical responders in a helicopter can provide both a higher level of care at the scene, faster transport to a specialist hospital and critical care during the journey. A disadvantage is that it can be dangerous and potentially not possible for them to fly at night or in bad weather.

Tactical (hazardous area)

Some EMS agencies have set up specialist teams to help those injured in a major incident or a dangerous situation. These include tactical police operations, active shooters, bombings, hazmat situations, building collapses, fires and natural disasters. In the US, these are often known as Tactical EMS teams and are often deployed alongside police SWAT teams. The equivalent in UK ambulance services is a Hazardous Area Response Team (HART).

Wilderness

Wilderness EMS-like systems (WEMS) have been developed to provide medical responses in remote areas, which may have significantly different needs to an urban area. Examples include the National Ski Patrol or the regional-responding Appalachian Search and Rescue Conference (USA based). Like traditional EMS providers, all wilderness emergency medical (WEM) providers must still operate under on-line or off-line medical oversight. To assist physicians in the skills necessary to provide this oversight, the Wilderness Medical Society and the National Association of EMS Physicians jointly supported the development in 2011 of a unique "Wilderness EMS Medical Director" certification course, which was cited by the Journal of EMS as one of the Top 10 EMS Innovations of 2011. Skills taught in WEMT courses exceeding the EMT-Basic scope of practice include catheterization, antibiotic administration, use of intermediate Blind Insertion Airway Devices (i.e. King Laryngeal Tube), Nasogastric Intubation, and simple suturing; however, the scope of practice for the WEMT still falls under BLS level care. A multitude of organizations provide WEM training, including private schools, non-profit organizations such as the Appalachian Center for Wilderness Medicine and the Wilderness EMS Institute, military branches, community colleges and universities, EMS-college-hospital collaborations, and others.

Venom

From Wikipedia, the free encyclopedia
Wasp sting with a droplet of venom

Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved venom apparatus, such as fangs or a stinger, in a process called envenomation. Venom is often distinguished from poison, which is a toxin that is passively delivered by being ingested, inhaled, or absorbed through the skin, and toxungen, which is actively transferred to the external surface of another animal via a physical delivery mechanism.

Venom has evolved in terrestrial and marine environments and in a wide variety of animals: both predators and prey, and both vertebrates and invertebrates. Venoms kill through the action of at least four major classes of toxin, namely necrotoxins and cytotoxins, which kill cells; neurotoxins, which affect nervous systems; myotoxins, which damage muscles; and haemotoxins, which disrupt blood clotting. Venomous animals cause tens of thousands of human deaths per year.

Venoms are often complex mixtures of toxins of differing types. Toxins from venom are used to treat a wide range of medical conditions including thrombosis, arthritis, and some cancers. Studies in venomics are investigating the potential use of venom toxins for many other conditions.

Evolution

The use of venom across a wide variety of taxa is an example of convergent evolution. It is difficult to conclude exactly how this trait came to be so intensely widespread and diversified. The multigene families that encode the toxins of venomous animals are actively selected, creating more diverse toxins with specific functions. Venoms adapt to their environment and victims and accordingly evolve to become maximally efficient on a predator's particular prey (particularly the precise ion channels within the prey). Consequently, venoms become specialized to an animal's standard diet.

Mechanisms

Phospholipase A2, an enzyme in bee venom, releases fatty acids, affecting calcium signalling.

Venoms cause their biological effects via the many toxins that they contain; some venoms are complex mixtures of toxins of differing types. Major classes of toxin in venoms include:

Taxonomic range

Venom is widely distributed taxonomically, being found in both invertebrates and vertebrates, in aquatic and terrestrial animals, and among both predators and prey. The major groups of venomous animals are described below.

Arthropods

Venomous arthropods include spiders, which use fangs on their chelicerae to inject venom; and centipedes, which use forcipules, modified legs, to deliver venom; while scorpions and stinging insects inject venom with a sting. In bees and wasps, the sting is a modified egg-laying device – the ovipositor. In Polistes fuscatus, the female continuously releases a venom that contains a sex pheromone that induces copulatory behavior in males. In wasps such as Polistes exclamans, venom is used as an alarm pheromone, coordinating a response with from the nest and attracting nearby wasps to attack the predator. In some species, such as Parischnogaster striatula, venom is applied all over the body as an antimicrobial protection.

Many caterpillars have defensive venom glands associated with specialized bristles on the body called urticating hairs. These are usually merely irritating, but those of the Lonomia moth can be fatal to humans.

Bees synthesize and employ an acidic venom (apitoxin) to defend their hives and food stores, whereas wasps use a chemically different venom to paralyse prey, so their prey remains alive to provision the food chambers of their young. The use of venom is much more widespread than just these examples; many other insects, such as true bugs and many ants, also produce venom. The ant species Polyrhachis dives uses venom topically for the sterilisation of pathogens.

Other invertebrates

The fingernail-sized box jellyfish Malo kingi has among the most dangerous venom of any animal, causing Irukandji syndrome – severe pain, vomiting, and rapid rise in blood pressure.

There are venomous invertebrates in several phyla, including jellyfish such as the dangerous box jellyfish, the Portuguese man-of-war (a siphonophore) and sea anemones among the Cnidaria, sea urchins among the Echinodermata, and cone snails and cephalopods, including octopuses, among the Molluscs.

Vertebrates

Fish

Venom is found in some 200 cartilaginous fishes, including stingrays, sharks, and chimaeras; the catfishes (about 1000 venomous species); and 11 clades of spiny-rayed fishes (Acanthomorpha), containing the scorpionfishes (over 300 species), stonefishes (over 80 species), gurnard perches, blennies, rabbitfishes, surgeonfishes, some velvetfishes, some toadfishes, coral crouchers, red velvetfishes, scats, rockfishes, deepwater scorpionfishes, waspfishes, weevers, and stargazers.

Amphibians

Some salamanders can extrude sharp venom-tipped ribs. Two frog species in Brazil have tiny spines around the crown of their skulls which, on impact, deliver venom into their targets.

Reptiles

The venom of the prairie rattlesnake, Crotalus viridis (left), includes metalloproteinases (example on the bottom) which help digest prey before eating.

Some 450 species of snake are venomous. Snake venom is produced by glands below the eye (the mandibular glands) and delivered to the target through tubular or channeled fangs. Snake venoms contain a variety of peptide toxins, including proteases, which hydrolyze protein peptide bonds; nucleases, which hydrolyze the phosphodiester bonds of DNA; and neurotoxins, which disrupt signalling in the nervous system. Snake venom causes symptoms including pain, swelling, tissue necrosis, low blood pressure, convulsions, haemorrhage (varying by species of snake), respiratory paralysis, kidney failure, coma, and death. Snake venom may have originated with duplication of genes that had been expressed in the salivary glands of ancestors.

Venom is found in a few other reptiles such as the Mexican beaded lizard, the gila monster, and some monitor lizards, including the Komodo dragon. Mass spectrometry showed that the mixture of proteins present in their venom is as complex as the mixture of proteins found in snake venom. Some lizards possess a venom gland; they form a hypothetical clade, Toxicofera, containing the suborders Serpentes and Iguania and the families Varanidae, Anguidae, and Helodermatidae.

Mammals

Euchambersia, an extinct genus of therocephalians, is hypothesized to have had venom glands attached to its canine teeth.

A few species of living mammals are venomous, including solenodons, shrews, vampire bats, male platypuses, and slow lorises. Shrews have venomous saliva and most likely evolved their trait similarly to snakes. The presence of tarsal spurs akin to those of the platypus in many non-therian Mammaliaformes groups suggests that venom was an ancestral characteristic among mammals.

Extensive research on platypuses shows that their toxin was initially formed from gene duplication, but data provides evidence that the further evolution of platypus venom does not rely as much on gene duplication as was once thought. Modified sweat glands are what evolved into platypus venom glands. Although it is proven that reptile and platypus venom have independently evolved, it is thought that there are certain protein structures that are favored to evolve into toxic molecules. This provides more evidence of why venom has become a homoplastic trait and why very different animals have convergently evolved.

Venom and humans

Envenomation resulted in 57,000 human deaths in 2013, down from 76,000 deaths in 1990. Venoms, found in over 173,000 species, have potential to treat a wide range of diseases, explored in over 5,000 scientific papers.

In medicine, snake venom proteins are used to treat conditions including thrombosis, arthritis, and some cancers. Gila monster venom contains exenatide, used to treat type 2 diabetes. Solenopsins extracted from fire ant venom has demonstrated biomedical applications, ranging from cancer treatment to psoriasis. A branch of science, venomics, has been established to study the proteins associated with venom and how individual components of venom can be used for pharmaceutical means.

Resistance

The California ground squirrel is resistant to the Northern Pacific rattlesnake's powerful venom.

Venom is used as a trophic weapon by many predator species. The coevolution between predators and prey is the driving force of venom resistance, which has evolved multiple times throughout the animal kingdom. The coevolution between venomous predators and venom-resistant prey has been described as a chemical arms race. Predator/prey pairs are expected to coevolve over long periods of time. As the predator capitalizes on susceptible individuals, the surviving individuals are limited to those able to evade predation. Resistance typically increases over time as the predator becomes increasingly unable to subdue resistant prey. The cost of developing venom resistance is high for both predator and prey. The payoff for the cost of physiological resistance is an increased chance of survival for prey, but it allows predators to expand into underutilised trophic niches.

The California ground squirrel has varying degrees of resistance to the venom of the Northern Pacific rattlesnake. The resistance involves toxin scavenging and depends on the population. Where rattlesnake populations are denser, squirrel resistance is higher. Rattlesnakes have responded locally by increasing the effectiveness of their venom.

The kingsnakes of the Americas are constrictors that prey on many venomous snakes. They have evolved resistance which does not vary with age or exposure. They are immune to the venom of snakes in their immediate environment, like copperheads, cottonmouths, and North American rattlesnakes, but not to the venom of, for example, king cobras or black mambas.

Ocellaris clownfish always live among venomous sea anemone tentacles and are resistant to the venom.

Among marine animals, eels are resistant to sea snake venoms, which contain complex mixtures of neurotoxins, myotoxins, and nephrotoxins, varying according to species. Eels are especially resistant to the venom of sea snakes that specialise in feeding on them, implying coevolution; non-prey fishes have little resistance to sea snake venom.

Clownfish always live among the tentacles of venomous sea anemones (an obligatory symbiosis for the fish), and are resistant to their venom. Only 10 known species of anemones are hosts to clownfish and only certain pairs of anemones and clownfish are compatible. All sea anemones produce venoms delivered through discharging nematocysts and mucous secretions. The toxins are composed of peptides and proteins. They are used to acquire prey and to deter predators by causing pain, loss of muscular coordination, and tissue damage. Clownfish have a protective mucus that acts as a chemical camouflage or macromolecular mimicry preventing "not self" recognition by the sea anemone and nematocyst discharge. Clownfish may acclimate their mucus to resemble that of a specific species of sea anemone.

Antivenom

From Wikipedia, the free encyclopedia

Antivenom
Snake Milking.jpg
Milking a snake for the production of antivenom
 
Clinical data
Other namesantivenin, antivenene
AHFS/Drugs.comMonograph
Routes of
administration
injection
ATC code
Identifiers
ChemSpider
  • none

Antivenom, also known as antivenin, venom antiserum, and antivenom immunoglobulin, is a specific treatment for envenomation. It is composed of antibodies and used to treat certain venomous bites and stings. Antivenoms are recommended only if there is significant toxicity or a high risk of toxicity. The specific antivenom needed depends on the species involved. It is given by injection.

Side effects may be severe. They include serum sickness, shortness of breath, and allergic reactions including anaphylaxis. Antivenom is traditionally made by collecting venom from the relevant animal and injecting small amounts of it into a domestic animal. The antibodies that form are then collected from the domestic animal's blood and purified.

Versions are available for spider bites, snake bites, fish stings, and scorpion stings. Due to the high cost of producing antibody-based antivenoms and their short shelf lives when not refrigerated, alternative methods of production of antivenoms are being actively explored. One such different method of production involves production from bacteria. Another approach is to develop targeted drugs (which, unlike antibodies, are usually synthetic and easier to manufacture at scale).

Antivenom was first developed in the late 19th century and came into common use in the 1950s. It is on the World Health Organization's List of Essential Medicines.

Medical uses

Antivenom is used to treat certain venomous bites and stings. They are recommended only if there is significant toxicity or a high risk of toxicity. The specific antivenom needed depends on the venomous species involved.

In the US, approved antivenom, including for pit viper (rattlesnake, copperhead and water moccasin) snakebite, is based on a purified product made in sheep known as CroFab. It was approved by the FDA in October, 2000. U.S. coral snake antivenom is no longer manufactured, and remaining stocks of in-date antivenom for coral snakebite expired in the Fall of 2009, leaving the U.S. without a coral snake antivenom. Efforts are being made to obtain approval for a coral snake antivenom produced in Mexico which would work against U.S. coral snakebite, but such approval remains speculative.

As an alternative when conventional antivenom is not available, hospitals sometimes use an intravenous version of the antiparalytic drug neostigmine to delay the effects of neurotoxic envenomation through snakebite. Some promising research results have also been reported for administering the drug nasally as a "universal antivenom" for neurotoxic snakebite treatment.

A monovalent antivenom is specific for one toxin or species, while a polyvalent one is effective against multiple toxins or species.

The majority of antivenoms (including all snake antivenoms) are administered intravenously; however, stonefish and redback spider antivenoms are given intramuscularly. The intramuscular route has been questioned in some situations as not uniformly effective.

Antivenoms bind to and neutralize the venom, halting further damage, but do not reverse damage already done. Thus, they should be given as soon as possible after the venom has been injected, but are of some benefit as long as venom is present in the body. Since the advent of antivenoms, some bites which were previously invariably fatal have become only rarely fatal provided that the antivenom is given soon enough.

Side effects

Antivenoms are purified from animal serum by several processes and may contain other serum proteins that can act as immunogens. Some individuals may react to the antivenom with an immediate hypersensitivity reaction (anaphylaxis) or a delayed hypersensitivity (serum sickness) reaction, and antivenom should, therefore, be used with caution. Although rare, severe hypersensitivity reactions including anaphylaxis to antivenom are possible. Despite this caution, antivenom is typically the sole effective treatment for a life-threatening condition, and once the precautions for managing these reactions are in place, an anaphylactoid reaction is not grounds to refuse to give antivenom if otherwise indicated. Although it is a popular myth that a person allergic to horses "cannot" be given antivenom, the side effects are manageable, and antivenom should be given rapidly as the side effects can be managed.

Method of preparation

Most antivenoms are prepared by freeze drying (synonym, cryodesiccation, lyophilization). The process involves freezing the antisera, followed by application of high vacuum. This causes frozen water to sublimate. Sera is reduced to powder with no water content. In such an environment, microorganisms and enzymes cannot degrade the antivenom, and it can be stored for up to 5 years [at normal temperatures]. Liquid antivenoms may also be stored for 5 years, but they must be stored at low temperatures [<8 degrees Celsius (or 46 degrees Fahrenheit)].

Mechanism

Antivenoms act by binding to and neutralizing venoms. The principle of antivenom is based on that of vaccines, developed by Edward Jenner; however, instead of inducing immunity in the person directly, it is induced in a host animal and the hyperimmunized serum is transfused into the person. The host animals may include horses, donkeys, goats, sheep, rabbits, chickens, llamas, and camels. In addition, opossums are being studied for antivenom production. Antivenoms for medical use are often preserved as freeze-dried ampoules, but some are available only in liquid form and must be kept refrigerated. They are not immediately inactivated by heat, however, so a minor gap in the cold chain is not disastrous.

History

Surgeon-Major Edward Nicholson wrote in the November 1870 Madras Medical Journal that he had witnessed a Burmese snake-catcher inoculating himself with cobra venom. However, the snake-catcher was unsure whether this was actually effective and therefore continued to treat his snakes with care. Nicholson, along with other Britons, began to consider that venom might provide its own cure. Although Scottish surgeon Patrick Russell had noted in the late 18th century that snakes were not affected by their own venom, it was not until the late 19th century that Joseph Frayer, Lawrence Waddell, and others began to consider venom-based remedies again. However, they and other naturalists working in India did not have the funding to fully develop their theories. Not until 1895 did Sir Thomas Fraser, Professor of Medicine at the University of Edinburgh, pick up Fayrer and Waddell's research to produce a serum to act against cobra venom. His 'Antivenin' was effective, but failed to make an impact as the public were focused on contemporary Pasteurian discoveries.

Another anti-ophidic serum was developed by Albert Calmette, a French scientist of the Pasteur Institute working at its Indochine branch in 1895, to treat the bites of the Indian Cobra (Naja naja).

In 1901, Vital Brazil, working at the Instituto Butantan in São Paulo, Brazil, developed the first monovalent and polyvalent antivenoms for Central and South American Crotalus and Bothrops genera, as well as for certain species of venomous spiders, scorpions, and frogs.

In Australia, the Commonwealth Serum Laboratories (CSL) began antivenom research in the 1920s. CSL has developed antivenoms for the redback spider, funnel-web spiders and all deadly Australian snakes.

Availability

There is an overall shortage of antivenom to treat snakebites. Because of this shortage, clinical researchers are considering whether lower doses may be as effective as higher doses in severe neurotoxic snake envenoming.

Snake antivenom is complicated and expensive for manufacturers to produce. When weighed against profitability (especially for sale in poorer regions), the result is that many snake antivenoms, world-wide, are very expensive. Availability, from region to region, also varies.

Internationally, antivenoms must conform to the standards of pharmacopoeia and the World Health Organization (WHO). Antivenoms have been developed for the venoms associated with the following animals:

Spiders

Antivenom Species Country
Funnel web spider antivenom Sydney funnel-web spider Australia
Soro antiaracnidico Brazilian wandering spider Brazil
Soro antiloxoscelico Recluse spider Brazil
Suero antiloxoscelico Chilean recluse Chile
Aracmyn All species of Loxosceles and Latrodectus Mexico
Redback spider antivenom Redback spider Australia
Black widow spider (Latrodectus Mactans) antivenin (equine origin) Southern black widow spider United States
SAIMR spider antivenom Button spider South Africa
Anti-Latrodectus antivenom Black widow spider Argentina

Acarids

Antivenom Species Country
Tick antivenom Paralysis tick Australia

Insects

Antivenom Species Country
soro antilonomico Lonomia obliqua caterpillar Brazil

Scorpions

Antivenom Species Country
Scorpion Venom Anti Serum (India) Purified lyophilized enzyme refined Equine Immunoglobulins Buthus tamulus India
ANTISCORP - Premium (Scorpion Venom Antiserum North Africa) Purified lyophilized enzyme refined Equine Immunoglobulins Androctonus amoerexi and Leiurus quinquestraiatus India
INOSCORPI MENA (Middle East and North Africa) Androctonus australis, Androctonus mauritanicus, Androctonus crassicauda, Buthus occitanus mardochei, Buthus occitanus occitanus, Leiurus quinquestriatus quinquestriatus, Leiurus quinquestriatus hebreus Spain
Alacramyn Centruroides limpidus, C. noxius, C. suffusus Mexico
Suero Antialacran Centruroides limpidus, C. noxius, C. suffusus Mexico
Tunisian polyvalent antivenom All Iranian scorpions Tunisia
Anti-Scorpion Venom Serum I.P. (AScVS) Indian red scorpion India
Anti-scorpionique Androctonus spp., Buthus spp. Algeria
Scorpion antivenom Black scorpion, Buthus occitanus Morocco
Soro antiscorpionico Tityus spp. Brazil
SAIMR scorpion antivenin Parabuthus spp. South Africa
Purified prevalent Anti-Scorpion Serum (equine source) Leiurus spp. and Androctonus scorpions Egypt

Marine animals

Antivenom Species Country
CSL box jellyfish antivenom Box jellyfish Australia
CSL stonefish antivenom Stonefish Australia

Snakes

Antivenom Species Country
PANAF PREMIUM (Sub-Sahara Africa) Purified lyophilized enzyme refined Equine Immunoglobulins  Echis ocellatus, Echis leucogaster, Echis carinatus, Bitis arietans, Bitis rhinoceros, Bitis nasicornis, Bitis gabonica, Dendroaspis polylepis, Dendroaspis viridis, Dendroaspis angusticeps, Dendroaspis jamesoni, Naja nigricollis, Naja melanoleuca and Naja haje India
Snake Venom Antiserum (India) Purified lyophilized enzyme refined Equine Immunoglobulins Naja naja, Vipera russelii and Echis carinatus India
INOSERP MENA (Middle East and North Africa) Bitis arietans, Cerastes cerastes, Cerastes gasperettii,Cerastes vipera, Daboia deserti, Daboia mauritanica, Daboia palaestinae, Echis carinatus sochureki, Echis coloratus, Echis khosatzkii, Echis leucogaster, Echis megalocephalus, Echis omanensis, Echis pyramidum, Macrovipera lebetina obtusa, Macrovipera lebetina transmediterranea, Macrovipera lebetina turanica, Montivipera bornmuelleri, Montivipera raddei kurdistanica, Pseuocerastes fieldi, Pseudocerastes persicus, Vipera latastei, Naja haje, Naja nubiae, Naja pallida and Walterinnesia aegyptia Spain
INOSERP PAN-AFRICA (Sub-Sahara Africa) Echis ocellatus, Bitis arietans, Dendroaspis polylepis and Naja nigricollis Spain
EchiTAbG (Sub-Sahara Africa)[33] Echis ocellatus, Echis pyramidum Wales, UK
Polyvalent snake antivenom ANAVIP South American rattlesnake Crotalus durissus and fer-de-lance Bothrops asper Mexico (Instituto Bioclon); South America
Polyvalent snake antivenom Saw-scaled viper Echis carinatus, Russell's viper Daboia russelli, spectacled cobra Naja naja, common krait Bungarus caeruleus India
Death adder antivenom Death adder Australia
Taipan antivenom Taipan Australia
Black snake antivenom Pseudechis spp. Australia
Tiger snake antivenom Australian copperheads, tiger snakes, Pseudechis spp., rough-scaled snake Australia
Brown snake antivenom Brown snakes Australia
Polyvalent snake antivenom Australian snakes as listed above Australia
Sea snake antivenom Sea snakes Australia
Vipera tab Vipera spp. UK
Polyvalent crotalid antivenin (CroFab—Crotalidae Polyvalent Immune Fab (Ovine)) North American pit vipers (all rattlesnakes, copperheads, and cottonmouths) North America
Soro antibotropicocrotalico Pit vipers and rattlesnakes Brazil
Antielapidico Coral snakes Brazil
SAIMR polyvalent antivenom Mambas, cobras, Rinkhalses, puff adders (Unsuitable small adders: B. worthingtoni, B. atropos, B. caudalis, B. cornuta, B. heraldica, B. inornata, B. peringueyi, B. schneideri, B. xeropaga) South Africa
SAIMR echis antivenom Saw-scaled vipers South Africa
SAIMR Boomslang antivenom Boomslang South Africa
Panamerican serum Coral snakes Costa Rica
Anticoral Coral snakes Costa Rica
Anti-mipartitus antivenom Coral snakes Costa Rica
Anticoral monovalent Coral snakes Costa Rica
Antimicrurus Coral snakes Argentina
Coralmyn Coral snakes Mexico
Anti-micruricoscorales Coral snakes Colombia
crotalidae immune F(ab')2 (equine)) (Anavip) North American species of Crotalinae US

Terminology

The name "antivenin" comes from the French word venin, meaning venom, which in turn was derived from Latin venenum, meaning poison.

Historically, the term antivenin was predominant around the world, its first published use being in 1895. In 1981, the World Health Organization decided that the preferred terminology in the English language would be venom and antivenom rather than venin and antivenin or venen and antivenene.

Recombinant antibodies

From Wikipedia, the free encyclopedia

Recombinant antibodies are antibody fragments produced by using recombinant antibody coding genes. They mostly consist of a heavy and light chain of the variable region of immunoglobulin. Recombinant antibodies have many advantages in both medical and research applications, which make them a popular subject of exploration and new production against specific targets. The most commonly used form is the single chain variable fragment (scFv), which has shown the most promising traits exploitable in human medicine and research. In contrast to monoclonal antibodies produced by hybridoma technology, which may lose the capacity to produce the desired antibody over time or the antibody may undergo unwanted changes, which affect its functionality, recombinant antibodies produced in phage display maintain high standard of specificity and low immunogenicity.

Structure and characterization

Formats

There are several known formats of recombinant antibodies which are commonly produced. These are the Fab recombinant antibodies, scFv and diabodies. Each of the formats has a slightly different potential in applications and may be used in various fields of research as well as human and animal medicine. Another researched possibility is the development of anti-idiotypic antibodies. Anti-idiotypic antibodies bind to a paratope of another specific antibody. Therefore, it can be used for measuring presence of antibodies and drug loads in patients' sera. Based on their binding specificity 3 types of anti-idiotypic antibodies can be distinguished, which partially overlap with the previously mentioned formats: the classical ones, a group including Fab fragment antibodies, antibodies binding to idiotope outside of the drug binding site and antibodies, which only bind to the already assembled complex of drug bound to the target. The most commonly used are the scFv, Fab fragments and bispecific antibodies.

Single chain variable fragment (scFv)

scFv is the smallest of the recombinant antibody formats, which is capable of antigen binding. They have a molecular weight of approximately 27kDa. They are formed by light and heavy chain of the variable region of an immunoglobulin. The two chains are linked by a flexible peptide linker. The flexible peptide linker usually consists of short sequence repetition. The sequence is made up of four glycines and a serine and it serves the purpose of stabilization of the fragment. The functionality may be enhanced by site-specific chemical modifications, adding a peptide-tag or by fusion with a gene to achieve production of bifunctional recombinant antibodies. It is important to establish the binding activity in order to ensure good functionality of the product. To determine the binding activity, ELISA assay is routinely performed.

Fab fragments

Structurally Fab fragments consist of two sets of variable and constant components, which create two polypetide chains. Together they form a stable structure. As a member of the anti-idiotypic antibodies, Fab fragment recombinant antibodies bind directly to the paratope of the target antibody. That means that they compete with the drug for binding site and have an inhibitory function. Fab fragment antibodies can be used for detection of not bound drugs or free drugs in the serum. Fab antibodies have also been used to avoid the adverse effects caused by unspecific binding of the Fc portion of the antibody, which is missing in the Fab fragment. In case the IgG immunoglobulin was more suitable for the treatment or some other particular application, experiments have also been conducted, in which the recombinant Fab fragments were converted into recombinant IgG form. This possibility further broadens the pool of potential target structures.

Bispecific recombinant antibodies

Along scFv and Fab fragments, diabodies or bispecific recombinant antibodies are the third major format. Bispecific antibodies combine two different antigen binding specificities within one molecule. The bispecific antibodies are used to crosslink the target molecules with two different cells and mediate direct cytotoxicity.

Production and development

Production of recombinant antibodies

The production of recombinant antibodies follows principally similar workflow. It consists of determining the sequence of the desired product followed by refinement of the codon, then gene synthesis and construct generation. Once the construct is delivered to the laboratory, expression constructs are produced, then they are transferred to a cell culture in the process called transfection and once the cell culture produces the desired recombinant antibody, it is regularly collected, purified and analyzed or used for further experimentation. For recombinant antibody production the stable cell lines such as CHO and HEK293 are used. Optimizations of mammalian cell cultures have led to increase the yield of antibodies from HEK293 or CHO cell lines to over 12g/liter. In the beginning phases of the recombinant antibody production it was important to achieve the assembly of a functional Fv fragment in Escherichia coli. The correct fold is essential for functionality of the antibody. Second essential prerequisite for the modern day production of scFv was the successful assembly of recombinant antibodies from heavy and light chain of immunoglobulin. These two experiments allowed for further development and refinement of the recombinant antibodies until modern day form. Today's in vitro production process eliminates the need for laboratory animals. Using a synthetic or human Ab library, as opposed to immunization of animals and the subsequent generation of stable hybridoma cell lines, requires fewer resources and produces less waste, making the entire process more sustainable. 

Hybridoma

Monoclonal antibodies are essential for many therapies applied today in human medicine. The first successful technology which was robust and led to a stable production of desired antibodies was hybridoma technology. The hybridoma cell lines, which produced large quantities of relatively pure and predictable antibodies was first introduced in 1975. Since then, it has been used for various purposes scaling from diagnostic and therapeutic to research applications. Despite its indisputable role in scientific discoveries and numerous treatment strategies, the hybridoma technology presents researchers with some obstacles such as ethical issues, potential to lose expression of the target protein or lengthy production and most importantly the development of HAMA in patients as mentioned previously. Therefore, different methods need to complement or even partially replace the hybridoma. Hybridomas are an essential part of the recombinant antibody generation even today as they are still used to produce the monoclonal antibodies, from which the Fab fragments, scFv or somatically fused antibodies create a bispecific antibody.

Phage display

The most commonly applied technology to produce recombinant antibodies in the laboratory settings today is the phage display. Phage display is a method, in which the target recombinant antibody is produced on the surface of a bacteriophage. This allows for a fast recombinant antibody production and easy manipulation in the laboratory conditions. Both scFv and Fab fragment recombinant antibodies are routinely produced using the antibody phage display. From all the possible phage display systems, the most common is the Escherichia coli, due to its rapid growth and division rate and cheap set up and maintenance.

Engineering and development

Two main strategies have been described to engineer the scFv fragments. The first one is the so-called non-colinear approach. It works on the principle of heterodimerization of two chains. Non-colinear approach leads to production of diabodies and recombinant antibodies, which combine two specificities. The second approach is called colinear and it described the process of fusion of two different scFv with a biologically active protein.

Medical and research applications

Recombinant antibodies fulfill a large spectrum of functions spanning from research to diagnosis and treatment therapies for various diseases. Their specificity and low immunogenicity make them a great alternative to traditional forms of treatment, increasing the accuracy of targeting specific molecules and avoiding adverse side effects.

Recombinant antibodies have been explored as a treatment for cancer, HIV, herpes simplex virus (HSV) and more. ScFv have been a part of the highly promising therapeutic approach of universal chimeric antigen receptors (uniCAR) technology, which shows promising results. The scFv are part of the technology in the form of target modules, which direct the immune response to specific cancer cells, expressing the target antigen. In case of research into HIV treatment, the recombinant antibodies are rather used for their neutralizing quality. The same goes for HSV infection. Specific recombinant antibodies are designed to bind with to surface heparin sulphate proteoglycan (HSP), which complicates or even disables the entry of the HSV into the host cell. This is a method which significantly decreases the severity of HSV infection.

As was mentioned in the beginning of this section, recombinant antibodies can also be used in diagnosis, an example of such diagnostic application is the detection of rabies virus. Since the current diagnostic antibodies are not as accurate as would be desired, the recombinant antibodies offer a promising alternative. In case of rabies infection, which is only treatable shortly after exposure, accurate and precise diagnosis is vital for survival of the patient. In comparison to commercially produced and commonly available antibodies, the recombinant antibodies are cheaper to produce and more accurate in determining the infection. Another advantage of the recombinant antibody is the potential application as a neutralizing antibody as part of the subsequent treatment.

The potential of recombinant antibodies in human and animal medicine is immense as shown even by the few selected examples. As mentioned previously the recombinant antibodies and especially those, which have been developed in phage display are highly specific, have great pharmacokinetics and could be used in wide range of treatments. However, it is important to realize that it is not expected or desired for the recombinant antibodies created in phage display to completely replace the hybridoma antibody production but rather to complement it.

Advantages of using recombinant antibodies

Recombinant antibodies bring many advantages with their application in human medicine and research. The first one is the complete elimination of ethical issues because there is no need for animal immunization. The cultivation of CHO cells for recombinant antibody expression is a popular strategy for antibody producers since the cell structure is similar to that of the human body. Thanks to their size, which is smaller than complete antibody and particularly than 2000 nm, yet not smaller than 8 nm they are cleared from the organism with ease and in a timely manner, through the renal pathway, which is the desirable clearance. Another great advantage is their monovalency, which means that they are highly specific and bind to a single antigen. Researchers have managed to produce antibodies carrying no other activity than the antigen binding. Since the recombinant antibodies are sequence defined they are more reliable as well as reproducible. In combination with their small size the great specificity can be exploited to deliver highly specific drug to a specific site precisely because the small size predisposes the recombinant antibodies to penetrate tissues more easily. It has been reported that the recombinant antibodies penetrate tumor tissue better than the full-length IgG immunoglobulins. The small size also adds to better biodistribution in the patient. In comparison to antibodies derived from hybridoma cell lines the recombinant antibodies do not cause immunogenicity, the infamous human anti-mouse antibody (HAMA). Further advantages show afucosylated recombinant antibodies which are used successfully in the fight against cancer.

These were the top advantages for use in patients. However, the use of recombinant antibodies is also advantageous compared to traditional monoclonal antibodies derived from hybridoma cell lines during their production as well. The production is much faster and we have better control over the process than in hybridoma technology. Moreover, the recombinant antibodies may be designed virtually against any antigen, of the proper size and shape, but they are not solely limited to the peptide nature of an antigen. The recombinant antibodies may also be used in fused form with drugs and/or toxins, which may be further exploited in the medical applications. Last but not least of their advantages during production is the possibility to optimize and genetically engineer the recombinant antibodies based on the current demand of the patient or researcher. An experienced technician is required to perform the phage display and third it is almost inevitable to include outsource companies in the process for the gene synthesis and construct generation. However, in a systematic comparison of animal derived antibodies verus phage display derived recombinant antibodies used for research and diagnostic applications, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) released a recommendation in favor of on non-animal derived antibodies in May 2020, mainly based on the fact that in contrast to animal derived antibodies, recombinant antibodies are always sequence defined protein reagents, allowing to eliminate some of the quality issues attributed to current research antibodies when made in animals.

Significant other

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