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Monday, February 6, 2023

Phage display


From Wikipedia, the free encyclopedia
Phage display cycle. 1) fusion proteins for a viral coat protein + the gene to be evolved (typically an antibody fragment) are expressed in bacteriophage. 2) the library of phage are washed over an immobilised target. 3) the remaining high-affinity binders are used to infect bacteria. 4) the genes encoding the high-affinity binders are isolated. 5) those genes may have random mutations introduced and used to perform another round of evolution. The selection and amplification steps can be performed multiple times at greater stringency to isolate higher-affinity binders.

Phage display is a laboratory technique for the study of protein–protein, proteinpeptide, and protein–DNA interactions that uses bacteriophages (viruses that infect bacteria) to connect proteins with the genetic information that encodes them. In this technique, a gene encoding a protein of interest is inserted into a phage coat protein gene, causing the phage to "display" the protein on its outside while containing the gene for the protein on its inside, resulting in a connection between genotype and phenotype. These displaying phages can then be screened against other proteins, peptides or DNA sequences, in order to detect interaction between the displayed protein and those other molecules. In this way, large libraries of proteins can be screened and amplified in a process called in vitro selection, which is analogous to natural selection.

The most common bacteriophages used in phage display are M13 and fd filamentous phage, though T4, T7, and λ phage have also been used.

History

Phage display was first described by George P. Smith in 1985, when he demonstrated the display of peptides on filamentous phage (long, thin viruses that infect bacteria) by fusing the virus's capsid protein to one peptide out of a collection of peptide sequences. This displayed the different peptides on the outer surfaces of the collection of viral clones, where the screening step of the process isolated the peptides with the highest binding affinity. In 1988, Stephen Parmley and George Smith described biopanning for affinity selection and demonstrated that recursive rounds of selection could enrich for clones present at 1 in a billion or less. In 1990, Jamie Scott and George Smith described creation of large random peptide libraries displayed on filamentous phage. Phage display technology was further developed and improved by groups at the Laboratory of Molecular Biology with Greg Winter and John McCafferty, The Scripps Research Institute with Richard Lerner and Carlos Barbas and the German Cancer Research Center with Frank Breitling and Stefan Dübel for display of proteins such as antibodies for therapeutic protein engineering. Smith and Winter were awarded a half share of the 2018 Nobel Prize in chemistry for their contribution to developing phage display. A patent by George Pieczenik claiming priority from 1985 also describes the generation of peptide libraries.

Principle

Like the two-hybrid system, phage display is used for the high-throughput screening of protein interactions. In the case of M13 filamentous phage display, the DNA encoding the protein or peptide of interest is ligated into the pIII or pVIII gene, encoding either the minor or major coat protein, respectively. Multiple cloning sites are sometimes used to ensure that the fragments are inserted in all three possible reading frames so that the cDNA fragment is translated in the proper frame. The phage gene and insert DNA hybrid is then inserted (a process known as "transduction") into E. coli bacterial cells such as TG1, SS320, ER2738, or XL1-Blue E. coli. If a "phagemid" vector is used (a simplified display construct vector) phage particles will not be released from the E. coli cells until they are infected with helper phage, which enables packaging of the phage DNA and assembly of the mature virions with the relevant protein fragment as part of their outer coat on either the minor (pIII) or major (pVIII) coat protein. By immobilizing a relevant DNA or protein target(s) to the surface of a microtiter plate well, a phage that displays a protein that binds to one of those targets on its surface will remain while others are removed by washing. Those that remain can be eluted, used to produce more phage (by bacterial infection with helper phage) and to produce a phage mixture that is enriched with relevant (i.e. binding) phage. The repeated cycling of these steps is referred to as 'panning', in reference to the enrichment of a sample of gold by removing undesirable materials. Phage eluted in the final step can be used to infect a suitable bacterial host, from which the phagemids can be collected and the relevant DNA sequence excised and sequenced to identify the relevant, interacting proteins or protein fragments.

The use of a helper phage can be eliminated by using 'bacterial packaging cell line' technology.

Elution can be done combining low-pH elution buffer with sonification, which, in addition to loosening the peptide-target interaction, also serves to detach the target molecule from the immobilization surface. This ultrasound-based method enables single-step selection of a high-affinity peptide.

Applications

Applications of phage display technology include determination of interaction partners of a protein (which would be used as the immobilised phage "bait" with a DNA library consisting of all coding sequences of a cell, tissue or organism) so that the function or the mechanism of the function of that protein may be determined. Phage display is also a widely used method for in vitro protein evolution (also called protein engineering). As such, phage display is a useful tool in drug discovery. It is used for finding new ligands (enzyme inhibitors, receptor agonists and antagonists) to target proteins. The technique is also used to determine tumour antigens (for use in diagnosis and therapeutic targeting) and in searching for protein-DNA interactions using specially-constructed DNA libraries with randomised segments. Recently, phage display has also been used in the context of cancer treatments - such as the adoptive cell transfer approach. In these cases, phage display is used to create and select synthetic antibodies that target tumour surface proteins. These are made into synthetic receptors for T-Cells collected from the patient that are used to combat the disease.

Competing methods for in vitro protein evolution include yeast display, bacterial display, ribosome display, and mRNA display.

Antibody maturation in vitro

The invention of antibody phage display revolutionised antibody drug discovery. Initial work was done by laboratories at the MRC Laboratory of Molecular Biology (Greg Winter and John McCafferty), the Scripps Research Institute (Richard Lerner and Carlos F. Barbas) and the German Cancer Research Centre (Frank Breitling and Stefan Dübel). In 1991, The Scripps group reported the first display and selection of human antibodies on phage. This initial study described the rapid isolation of human antibody Fab that bound tetanus toxin and the method was then extended to rapidly clone human anti-HIV-1 antibodies for vaccine design and therapy.

Phage display of antibody libraries has become a powerful method for both studying the immune response as well as a method to rapidly select and evolve human antibodies for therapy. Antibody phage display was later used by Carlos F. Barbas at The Scripps Research Institute to create synthetic human antibody libraries, a principle first patented in 1990 by Breitling and coworkers (Patent CA 2035384), thereby allowing human antibodies to be created in vitro from synthetic diversity elements.

Antibody libraries displaying millions of different antibodies on phage are often used in the pharmaceutical industry to isolate highly specific therapeutic antibody leads, for development into antibody drugs primarily as anti-cancer or anti-inflammatory therapeutics. One of the most successful was adalimumab, discovered by Cambridge Antibody Technology as D2E7 and developed and marketed by Abbott Laboratories. Adalimumab, an antibody to TNF alpha, was the world's first fully human antibody to achieve annual sales exceeding $1bn.

General protocol

Below is the sequence of events that are followed in phage display screening to identify polypeptides that bind with high affinity to desired target protein or DNA sequence:

  1. Target proteins or DNA sequences are immobilized to the wells of a microtiter plate.
  2. Many genetic sequences are expressed in a bacteriophage library in the form of fusions with the bacteriophage coat protein, so that they are displayed on the surface of the viral particle. The protein displayed corresponds to the genetic sequence within the phage.
  3. This phage-display library is added to the dish and after allowing the phage time to bind, the dish is washed.
  4. Phage-displaying proteins that interact with the target molecules remain attached to the dish, while all others are washed away.
  5. Attached phage may be eluted and used to create more phage by infection of suitable bacterial hosts. The new phage constitutes an enriched mixture, containing considerably less irrelevant phage (i.e. non-binding) than were present in the initial mixture.
  6. Steps 3 to 5 are optionally repeated one or more times, further enriching the phage library in binding proteins.
  7. Following further bacterial-based amplification, the DNA within in the interacting phage is sequenced to identify the interacting proteins or protein fragments.

Selection of the coat protein

Filamentous phages

pIII

pIII is the protein that determines the infectivity of the virion. pIII is composed of three domains (N1, N2 and CT) connected by glycine-rich linkers. The N2 domain binds to the F pilus during virion infection freeing the N1 domain which then interacts with a TolA protein on the surface of the bacterium. Insertions within this protein are usually added in position 249 (within a linker region between CT and N2), position 198 (within the N2 domain) and at the N-terminus (inserted between the N-terminal secretion sequence and the N-terminus of pIII). However, when using the BamHI site located at position 198 one must be careful of the unpaired Cysteine residue (C201) that could cause problems during phage display if one is using a non-truncated version of pIII.

An advantage of using pIII rather than pVIII is that pIII allows for monovalent display when using a phagemid (plasmid derived from Ff phages) combined with a helper phage. Moreover, pIII allows for the insertion of larger protein sequences (>100 amino acids) and is more tolerant to it than pVIII. However, using pIII as the fusion partner can lead to a decrease in phage infectivity leading to problems such as selection bias caused by difference in phage growth rate or even worse, the phage's inability to infect its host. Loss of phage infectivity can be avoided by using a phagemid plasmid and a helper phage so that the resultant phage contains both wild type and fusion pIII.

cDNA has also been analyzed using pIII via a two complementary leucine zippers system, Direct Interaction Rescue or by adding an 8-10 amino acid linker between the cDNA and pIII at the C-terminus.

pVIII

pVIII is the main coat protein of Ff phages. Peptides are usually fused to the N-terminus of pVIII. Usually peptides that can be fused to pVIII are 6-8 amino acids long. The size restriction seems to have less to do with structural impediment caused by the added section and more to do with the size exclusion caused by pIV during coat protein export. Since there are around 2700 copies of the protein on a typical phages, it is more likely that the protein of interest will be expressed polyvalently even if a phagemid is used. This makes the use of this protein unfavorable for the discovery of high affinity binding partners.

To overcome the size problem of pVIII, artificial coat proteins have been designed. An example is Weiss and Sidhu's inverted artificial coat protein (ACP) which allows the display of large proteins at the C-terminus. The ACP's could display a protein of 20kDa, however, only at low levels (mostly only monovalently).

pVI

pVI has been widely used for the display of cDNA libraries. The display of cDNA libraries via phage display is an attractive alternative to the yeast-2-hybrid method for the discovery of interacting proteins and peptides due to its high throughput capability. pVI has been used preferentially to pVIII and pIII for the expression of cDNA libraries because one can add the protein of interest to the C-terminus of pVI without greatly affecting pVI's role in phage assembly. This means that the stop codon in the cDNA is no longer an issue. However, phage display of cDNA is always limited by the inability of most prokaryotes in producing post-translational modifications present in eukaryotic cells or by the misfolding of multi-domain proteins.

While pVI has been useful for the analysis of cDNA libraries, pIII and pVIII remain the most utilized coat proteins for phage display.

pVII and pIX

In an experiment in 1995, display of Glutathione S-transferase was attempted on both pVII and pIX and failed. However, phage display of this protein was completed successfully after the addition of a periplasmic signal sequence (pelB or ompA) on the N-terminus. In a recent study, it has been shown that AviTag, FLAG and His could be displayed on pVII without the need of a signal sequence. Then the expression of single chain Fv's (scFv), and single chain T cell receptors (scTCR) were expressed both with and without the signal sequence.

PelB (an amino acid signal sequence that targets the protein to the periplasm where a signal peptidase then cleaves off PelB) improved the phage display level when compared to pVII and pIX fusions without the signal sequence. However, this led to the incorporation of more helper phage genomes rather than phagemid genomes. In all cases, phage display levels were lower than using pIII fusion. However, lower display might be more favorable for the selection of binders due to lower display being closer to true monovalent display. In five out of six occasions, pVII and pIX fusions without pelB was more efficient than pIII fusions in affinity selection assays. The paper even goes on to state that pVII and pIX display platforms may outperform pIII in the long run.

The use of pVII and pIX instead of pIII might also be an advantage because virion rescue may be undertaken without breaking the virion-antigen bond if the pIII used is wild type. Instead, one could cleave in a section between the bead and the antigen to elute. Since the pIII is intact it does not matter whether the antigen remains bound to the phage.

T7 phages

The issue of using Ff phages for phage display is that they require the protein of interest to be translocated across the bacterial inner membrane before they are assembled into the phage. Some proteins cannot undergo this process and therefore cannot be displayed on the surface of Ff phages. In these cases, T7 phage display is used instead. In T7 phage display, the protein to be displayed is attached to the C-terminus of the gene 10 capsid protein of T7.

The disadvantage of using T7 is that the size of the protein that can be expressed on the surface is limited to shorter peptides because large changes to the T7 genome cannot be accommodated like it is in M13 where the phage just makes its coat longer to fit the larger genome within it. However, it can be useful for the production of a large protein library for scFV selection where the scFV is expressed on an M13 phage and the antigens are expressed on the surface of the T7 phage.

Bioinformatics resources and tools

Databases and computational tools for mimotopes have been an important part of phage display study. Databases, programs and web servers have been widely used to exclude target-unrelated peptides, characterize small molecules-protein interactions and map protein-protein interactions. Users can use three dimensional structure of a protein and the peptides selected from phage display experiment to map conformational epitopes. Some of the fast and efficient computational methods are available online.

Good Samaritan law

From Wikipedia, the free encyclopedia
Legend:
  Good Samaritan law
  Duty to rescue law
  No duty to rescue or Good Samaritan law
  No duty to rescue, no data about Good Samaritan laws

Good Samaritan laws offer legal protection to people who give reasonable assistance to those who are, or whom they believe to be injured, ill, in peril, or otherwise incapacitated. The protection is intended to reduce bystanders' hesitation to assist, for fear of being sued or prosecuted for unintentional injury or wrongful death. An example of such a law in common-law areas of Canada: a Good Samaritan doctrine is a legal principle that prevents a rescuer who has voluntarily helped a victim in distress from being successfully sued for wrongdoing. Its purpose is to keep people from being reluctant to help a stranger in need for fear of legal repercussions should they make some mistake in treatment. By contrast, a duty to rescue law requires people to offer assistance and holds those who fail to do so liable.

Good Samaritan laws may vary from jurisdiction to jurisdiction, as do their interactions with various other legal principles, such as consent, parental rights and the right to refuse treatment. Most such laws do not apply to medical professionals' or career emergency responders' on-the-job conduct, but some extend protection to professional rescuers when they are acting in a volunteer capacity.

The principles contained in Good Samaritan laws more typically operate in countries in which the foundation of the legal system is English common law, such as Australia. In many countries that use civil law as the foundation for their legal systems, the same legal effect is more typically achieved using a principle of duty to rescue.

Good Samaritan laws take their name from a parable found in the Bible, attributed to Jesus, commonly referred to as the Parable of the Good Samaritan which is contained in Luke 10:29–37. It recounts the aid given by a traveller from the area known as Samaria to another traveller of a conflicting religious and ethnic background who had been beaten and robbed by bandits.

Regions

Good Samaritan laws tend to differ by region, as each is crafted based on local interpretations of the providers protected, as well as the scope of care covered.

Australia

Most Australian states and territories have some form of Good Samaritan protection. In general, these offer protection if care is made in good faith, and the "Good Samaritan" is not impaired by drugs or alcohol. Variations exist between states, from not applying if the "Good Samaritan" is the cause of the problem (New South Wales), to applying under all circumstances if the attempt is made in good faith (Victoria).

Belgium

The Belgian Good Samaritan Law imposes on anyone who is capable to aid a legal duty to help a person, who is in great danger, without putting himself or others in serious danger (article 422bis Criminal Code).

Canada

In Canada, good Samaritan acts fall under provincial jurisdiction. Each province has its own act, such as Ontario's and British Columbia's respective Good Samaritan Acts, Alberta's Emergency Medical Aid Act, and Nova Scotia's Volunteer Services Act. Only in Quebec, a civil law jurisdiction, does a person have a general duty to respond, as detailed in the Quebec Charter of Human Rights and Freedoms. a typical Canadian law is provided here, from Ontario's Good Samaritan Act, 2001, section 2:

Protection from liability

2. (1) Despite the rules of common law, a person described in subsection (2) who voluntarily and without reasonable expectation of compensation or reward provides the services described in that subsection is not liable for damages that result from the person's negligence in acting or failing to act while providing the services, unless it is established that the damages were caused by the gross negligence of the person. 2001, c. 2, s. 2 (1).

Yukon and Nunavut do not have good Samaritan laws.

China

There have been incidents in China, such as the Peng Yu incident in 2006, where good Samaritans who helped people injured in accidents were accused of having injured the victim themselves.

In 2011, a toddler called Wang Yue was killed when she was run over by two vehicles. The entire incident was caught on a video, which shows eighteen people seeing the child but refusing to help. In a November 2011 survey, a majority, 71%, thought that the people who passed the child without helping were afraid of getting into trouble themselves. Following the event, China Daily reported that "at least 10 Party and government departments and organizations in Guangdong, including the province's commission on politics and law, the women's federation, the Academy of Social Sciences, and the Communist Youth League, have started discussions on punishing those who refuse to help people who clearly need it." Officials of Guangdong province, along with many lawyers and social workers, also held three days of meetings in the provincial capital of Guangzhou to discuss the case. It was reported that various lawmakers of the province were drafting a good Samaritan law, which would "penalize people who fail to help in a situation of this type and indemnify them from lawsuits if their efforts are in vain". Legal experts and the public debated the idea in preparation for discussions and a legislative push. On 1 August 2013, the nation's first good Samaritan law went into effect in Shenzhen. On 1 October 2017, China's national Good Samaritan law came into force, Clause 184 in Civil Law General Principles.

Finland

The Finnish Rescue Act explicitly stipulates a duty to rescue as a "general duty to act" and "engage in rescue activities according to [one's] abilities". The Finnish Rescue Act thus includes a principle of proportionality which requires professionals to extend immediate aid further than laypersons.

The Finnish Criminal Code stipulates:

Section 15 – Neglect of rescue (578/1995)

A person who knows that another is in mortal danger or serious danger to his or her health, and does not give or procure such assistance that in view of his or her options and the nature of the situation can reasonably be expected, shall be sentenced for neglect of rescue to a fine or to imprisonment for at most six months.

France

In France, the law requires anyone to assist a person in danger or at the very least call for help. People who help are not liable for damages except if the damages are intentional or caused by a "strong" mistake. 

Germany

In Germany, failure to provide first aid to a person in need is punishable under § 323c of its criminal penal code. However, any help one provides cannot and will not be prosecuted even if it made the situation worse or did not fulfill specific first aid criteria. People are thus encouraged to help in any way possible, even if the attempt is not successful. Moreover, people providing first aid are covered by the German Statutory Accident Insurance in case they suffer injury, losses, or damages.

India

There were around 480,000 road accidents in India in 2016, out of which 150,000 were killed. The Good Samaritan law gives legal protection to the good samaritans who help accidents victims with emergency medical care within the 'Golden Hour'. People are thus encouraged to help in any way possible, even if the attempt is not successful.

Ireland

The Civil Law (Miscellaneous Provisions) Act of 2011 introduced legislation specifically addressing the liability of citizen good Samaritans or volunteers in the Republic of Ireland, without introducing a duty to intervene. This act provides for exemption from liability for a person, or voluntary organization, for anything done while providing "assistance, advice or care" to a person who is injured, in serious risk or danger of becoming injured or developing an illness (or apparently so). There are exclusions for cases of "bad faith" or "gross negligence" on behalf of the carer, and incidents relating to the negligent use of motor vehicles. This Act only addresses situations where there is no duty of care owed by the good Samaritan or the volunteer.

The pre-hospital emergency care council (PHECC) specifically addresses the good Samaritan section of the Civil Law Act of 2011 and states that "The use of skills and medications restricted to Registered Practitioners would be covered under the 'Good Samaritan' Act. This Act assumes that you had no intention to practice during this time and that you acted as a Good Samaritan, assisting until the Emergency Services arrive on scene and you can hand over."

Israel

In Israel, the law requires anyone to assist a person in danger or at the very least call for help. People who help in good faith are not liable for damages. Helpers are eligible for compensation for damages caused to them during their assistance.

Romania

In Romania, the health reform passed in 2006 states that persons without medical training offering basic first aid voluntarily at the indications of a medical dispatch office or from own knowledge of first aid maneuvers, acting in good will to preserve the life or health of another person cannot be held responsible under penal or civil law.

United Arab Emirates

In November 2020, the United Arab Emirates was the first Arab country to pass a Good Samaritan law.

United Kingdom

In the common law of England and Wales there is no criminal liability for failing to act in the event of another person being in danger; however, there are exceptions to this rule. In instances where there has been an assumption of responsibility by the bystander, a dangerous situation was created by them, or there is a contractual or statutory duty to act, criminal liability would be imposed on the bystander for their failure to take action.

The courts are reluctant to penalize people attempting rescue. The Social Action, Responsibility and Heroism Act 2015 helps protect 'good Samaritans' when considering a claim of negligence or a breach of duty.

United States

All fifty states and the District of Columbia have some type of Good Samaritan law. The details of good Samaritan laws/acts vary by jurisdiction, including who is protected from liability and under what circumstances.

The 1998 Aviation Medical Assistance Act also provided coverage for "Good Samaritans" while in flight (Section 5b).

Countries without a Good Samaritan law

The following countries have no Good Samaritan law:

Common features

Good Samaritan laws often sharing different combinations or interpretations of the similar features, which vary by region.

Duty to assist

In some jurisdictions, unless a caretaker relationship (such as a parent-child or doctor-patient relationship) exists prior to the illness or injury, or the "Good Samaritan" is responsible for the existence of the illness or injury, no person is required to give aid of any sort to a victim. Good Samaritan statutes in the states of Minnesota, Vermont and Rhode Island do require a person at the scene of an emergency to provide reasonable assistance to a person in need. This assistance may be to call 9-1-1. Violation of the duty-to-assist subdivision is a petty misdemeanour in Minnesota and may warrant a fine of up to $100 in Vermont. At least five other states, including California and Nevada, have seriously considered adding duty-to-assist subdivisions to their Good Samaritan statutes. New York's law provides immunity for those who assist in an emergency. The public policy behind the law is:

The furnishing of medical assistance in an emergency is a matter of vital concern affecting the public health, safety and welfare. Prehospital emergency medical care, the provision of prompt and effective communication among ambulances and hospitals[,] and safe and effective care and transportation of the sick and injured are essential public health services.

— N.Y. Public Health L. § 3000.

Imminent peril

Good Samaritan provisions are not universal in application. The legal principle of imminent peril may also apply. In the absence of imminent peril, the actions of a rescuer may be perceived by the courts to be reckless and not worthy of protection. To illustrate, a motor vehicle collision occurs, but there is no fire, no immediate life threat from injuries, and no danger of a second collision. If someone, with good intentions, causes injury by pulling the victim from the wreckage, a court may rule that Good Samaritan laws do not apply because the victim was not in imminent peril and hold the actions of the rescuer to be unnecessary and reckless.

Reward or compensation

Only first aid provided without the intention of reward or financial compensation is covered. Medical professionals are typically not protected by Good Samaritan laws when performing first aid in connection with their employment. Some states make specific provisions for trained medical professionals acting as volunteers and for members of volunteer rescue squads acting without expectation of remuneration. In Texas, a physician who voluntarily assisted in the delivery of an infant, and who proved that he had "no expectation of remuneration", had no liability for the infant's injuries due to allegedly ordinary negligence; there was "uncontroverted testimony that neither he nor any doctor in Travis County would have charged a fee to [the mother] or any other person under the circumstances of this case". It was significant that the doctor was not an employee of the attending physician, but was only visiting the hospital and had responded to a "Dr. Stork" page, and had not asked or expected to be paid.

Obligation to remain

If a responder begins rendering aid, he must not leave the scene until it is necessary to call for needed medical assistance, a rescuer of equal or higher ability takes over, or continuing to give aid is unsafe. This can be as simple as a lack of adequate protection against potential diseases, such as vinyl, latex, or nitrile gloves to protect against blood-borne pathogens. A responder is never legally compelled to take risks to aid another person. The responder is not legally liable for any harm to the person assisted, as long as the responder acted rationally, in good faith, and in accordance with their level of training.

Consent

The responder must obtain the consent of the patient, or of the legal guardian of a patient who is a minor, unless this is not possible; failing to do so may attract a charge of assault or battery.

Implied consent

Consent may be implied if an unattended patient is unconscious, delusional, intoxicated, or deemed mentally unfit to make decisions regarding his or her safety, or if the responder has a reasonable belief that this was so; courts tend to be very forgiving in adjudicating this, under the legal fiction that "peril invites rescue" (as in the rescue doctrine). The test in most jurisdictions is that of the "average, reasonable person". To illustrate, would the average, reasonable person in any of the states described above consent to receiving assistance in these circumstances is able to make a decision?

Consent may also be implied if the legal parent or guardian is not immediately reachable and the patient is not considered an adult.

Parental consent

If the victim is a minor, consent must come from a parent or guardian. However, if the legal parent or guardian is absent, unconscious, delusional, or intoxicated, consent is implied. A responder is not required to withhold life-saving treatment (e.g., CPR or the Heimlich maneuver) from a minor if the parent or guardian will not consent. The parent or guardian is then considered neglecting the minor, and consent for treatment is implied by default because neglect has been committed. Special circumstances may exist if child abuse is suspected (the courts will usually give immunity to those first responders who report what they reasonably consider to be evidence of child abuse or neglect, similar to that given to those who have an actual duty to report such abuse, such as teachers or counsellors).

Laws for first responders only

In some jurisdictions, Good Samaritan laws only protect those who have completed basic first aid training and are certified by health organizations, such as the American Heart Association, or American Red Cross, provided that they have acted within the scope of their training. In these jurisdictions, a person who is neither trained in first aid nor certified, and who performs first aid incorrectly, can be held legally liable for errors made. In other jurisdictions any rescuer is protected from liability so long as the responder acted rationally. In Florida, paramedics, EMTs, and emergency medical responders (first responders) are required by law to act under the Duty to Act law, which requires them to stop and give aid that falls within their practice.

Comparison with duty to rescue

Good Samaritan laws may be confused with the duty to rescue, as described above. U.S. and Canadian approaches to this issue differ. Under the common law, Good Samaritan laws provide a defense against torts arising from the attempted rescue. Such laws do not constitute a duty to rescue, such as exists in some civil law countries, and in the common law under certain circumstances. However, the duty to rescue where it exists may itself imply a shield from liability; for example, under the German law of Unterlassene Hilfeleistung (an offense not to provide first aid when necessary), a citizen is obliged to provide first aid when necessary and is immune from prosecution if assistance given in good faith turns out to be harmful. In Canada, all provinces with the exception of Quebec operate on the basis of English Common Law. Quebec operates a civil law system, based in part on the Napoleonic Code, and the principle of duty to rescue does apply. Similarly, in France anyone who fails to render assistance to a person in danger will be found liable before French courts (civil and criminal liability). The penalty for this offence in criminal courts is imprisonment and a fine (under article 223–6 of the Criminal Code) while in civil courts judges will order payment of pecuniary compensation to the victims.

To illustrate a variation in the concept of duty to rescue, in the Canadian province of Ontario, the Occupational Health and Safety Act provides all workers with the right to refuse to perform unsafe work. There are, however, specific exceptions to this right. When the "life, health or safety of another person is at risk", then specific groups, including "police officers, firefighters, or employees of a hospital, clinic or other type of medical worker (including EMS)" are specifically excluded from the right to refuse unsafe work.

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.

Neuropharmacology

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