**Breaking News** Is Ketamine Safe For EMS?


I recently came across a post on social media where a provider was asking about the use of ketamine when elevated ICP is suspected. The individual was virtually thrown around like a rag doll for asking a question that has been discussed on FaceBook a million times.

While I understand the frustration of peers, I also feel the frustration of the OP. I do not believe that the OP believes that ketamine should be banished, but more than likely he is in a system that has trepidation in the use of something out of the norm. While this is no dig on whatever service that may be, in reality, it is not that uncommon. The wheel of progress turns very slow in EMS.

With that being said, I had a young woman by the name of Courtney Graham reach out to me a month ago in regard to publishing a paper she wrote on the safety profile of ketamine. I initially felt that it was (as depicted above) "beating a dead horse," and filed it in the "possibly" file. After I came across this FaceBook thread I realized that a resource with ketamines safety profile would probably be a smart idea. If you already believe that ketamine isn't the devil, you probably can stop reading here. If you need to prove to yourself or system that it is a valuable tool in the toolbox, proceed.

Efficacy and Safety of Ketamine in Emergency Medicine

Traditional pain management and sedation in the prehospital setting has routinely been performed with opioids (such as Fentanyl or Morphine), and Benzodiazepines (like Versed, Ativan or Diazepam). These traditional means have been deemed effective and safe for use in the prehospital field, although like every medication that health care providers such as paramedics, can administer in the prehospital environment, these classes of medications come with potentially severe side effects if not handled or administered appropriately. With changes to the scope and availability of medications, Ketamine has gained traction once again in the Paramedic scope of practice as a useful medication for many traditional and non-traditional uses.

Ketamine, chemically known as, 2-(2-Chlorophenyl)-2-methylaminocyclohexanone hydrochloride, is a dissociative anesthetic, selective in the limbic system, antagonizing the N-methyl D-aspartate (NMDA) receptors throughout the body (Wood 2003). As it is currently understood, this drug  causes a dissociation from perceived pain and stimuli in the body from  being received I n the cerebral cortex. When administered in its correct dosages, normal brain stem and cerebral cortex functions remain normal,  however , the patient will not be able to feel or potentially remember the pain that they are currently enduring.  Unlike Ketamine, traditional means of analgesia, e.g. Morphine and Fentanyl, depress the cerebral cortex and brain stem leading to decreases in consciousness and respiratory drive.  

Isn't Ketamine a horse tranquilizer?

Ketamine has  had  many dogmas regarding its use, safety, and efficacy in emergency medicine. Ketamine’s potential for emergence reaction, safety profile,  and the adequate dosing for its ranges in analgesia (0.1-0.3mg/kg) and anesthesia (3-5mg/kg) are some of many factors of these reservations made by providers.  Many of these dogmas  formed  because of the multiple unknowns  regarding Ketamine’s total effects in the body. Its mechanism of action is  poorly understood  regarding how exactly Ketamine works in the bod y with a variety of theories accepted for use (Wood 2003, Buckland et al. 2017, Scaggs et al. 2016). Although Ketamine show s side effects  of bronchodilation,  it  is proven to be helpful in medical patients who are suffering from severe asthmatic episodes when routine medications and treatments to combat severe asthmatic episodes are ineffective.  

For the purpose of this article,  evaluation of these issues will  aid in providing a conclusion as to whether Ketamine should be considered safe and effective for its current use as well as determining if there is potential for benefit in a broader use.

Wide Therapeutic Window

Ketamine is known for its pain management and anesthetic properties. However, with new research and trials, Ketamine is proving to have a wide therapeutic window for treating patients. This therapeutic window is defined as the dose ranges that it can be administered in, as well as the reasons and benefits of administrations. The study performed by Wood (2003) looked at Ketamine’s pharmacological profile and mechanism in the body system with regards to its side effects, safety in use, and accidental overdoses. This study was observing the doses of 2mg/kg with maintenance of 10-45mcg/kg and 10mg/kg intramuscular route, with a half-life of 180 minutes (Wood, 2003). Wood further talks about a case of an accidental overdose where a patient was administered 10 times the intended dose for Ketamine with no adverse side effects or life-threatening outcomes to the patient. This case of accidental overdose, should be interpreted as an extreme, however, it highlights Ketamine’s unique safety profile, and accepted mechanism in disassociating the receiving patient without a high risk of negatively affecting and depressing the central nervous system. If this accidental overdose occurred using a traditional medication (Fentanyl, Morphine, Versed, Ativan, Diazepam), there would be serious and life-threatening consequences in airway management, hemodynamics and central nervous system depression.

In an unpublished, Retrospective Analysis of a Non-Randomized, Non-Controlled, Administration of Prehospital Ketamine in a Local Urban Level 1 Trauma Center Based Ambulance, 19  Paramedic s have utilized Ketamine in their practice  since 8 March 2017. The paramedic protocol dictates that Ketamine is to be administered at an analgesic dose of 0.15mg/kg to 0.3mg/kg, with  an administration route of intravenous  (IV), intramuscular (IM), or intraosseous (IO) (Kamin et al. 2018). As well as 4mg/kg IM, or 1-2mg/kg IV in the incidence of chemical restraint or sedation (Kamin et al. 2018). Based on the data, the most frequent reason for administration of Ketamine  was in the situation of chemical restraint, with  32 administrations . Pain management having 12 administrations, and other administrations for respiratory and cardiac emergencies totaled to three. Of the 49 included administrations, all were deemed effective in reaching a pain scale (0-10) drop from the patient’s reported baseline to under 4, or successfully sedated without serious respiratory compromise requiring Advanced Life Support airway management during the care rendered in the prehospital environment. With the administrations preformed no severe and or life-threatening side effects were noted during the prehospital care rendered. In this study, there were no severe or life-threatening side effects such as apnea, hypoxia or laryngospasm.

In the Buckland (2017) study, the use of sedation via Ketamine was studied. Of those Paramedics who had used Ketamine in the field, only 20% had used the medication more than once (Buckland et al. 2017). Furthermore, of those who used Ketamine, 96% of the administrations were successful in achieving the desired outcome, and only 14% of those had adverse reactions. Of the 14% the most severe of reactions occurred in 1%, (22 patients) of laryngospasm. This study shows and proves that even at the high-end doses of Ketamine there was a high success rate in achieving their intended outcome without harming the patient, in incidents where if no action was taken both the patient and providers could have ended up in harm's way.

Side Effects and Safety Concerns

Ketamine as compared to traditional medications has few side effects, and even fewer severe side effects that could negatively affect the patient. One of the side effects that has been deterring providers from utilizing Ketamine is the emergence reaction. The study by Wood (2003), reports on the negative side effect in the occurrence of emergence reactions that come from patients who are metabolizing high doses of Ketamine. Emergence reactions occur when patients who are partially dissociated from reality, and can now perceive reality, however, are still in an “out of body” like state  (Wood 2003). When this occurs in a loud and busy environment, such as an Emergency Department, can be extremely frightening to the patient  (Wood 2003). The solution to emergence reactions is to administer a benzodiazepine (Versed, Ativan, Diazepam) in low dose for the anxiety of partial dissociation. The  benzodiazepine  during the partial dissociation will lead the patient to remain in a calmer and safer state. 

The other severe potential side effect of Ketamine is laryngospasm. Laryngospasm is the most severe of the side effects because of how it will inhibit the patient's ability to breathe on their own, when the patient’s vocal cords spasm shut. This side effect is very rare, and hard to predict when it will happen or to what patient. In the Buckland et al. (2017) study, of those providers who used Ketamine, 96% of the administrations were successful in achieving the desired outcome, and only 14% of those had adverse reactions. Of the 14% the most severe of reactions occurred in 1%, (22 patients) of laryngospasm; however, no further information was provided as to why laryngospasm occurred, i.e. pushing the medication to fast via IV bolus, or underlying medical history (Buckland et al. 2017). However, there are steps that the providers can take in order to prevent or to be prepared for this, if it was to occur in the prehospital setting. Many times, in the prehospital setting it is considered routine patient care, and standard of practice for any patient being administered narcotics to have their respiratory drive monitor via End Tidal CO2 (ETCO2) readings.

ETCO2 will give a reading of the CO2 being exhaled by the patient as well as a box wave form noted in healthy patients on the cardiac monitor. With this the provider will also be able to see how fast or slow the patient is breathing with a corresponding heart rate and rhythm, SpO2 and blood pressures. ETCO2 will be able to give the provider administering Ketamine a heads up if the patient suddenly stops breathing during administration. Providers are also trained to administer IV doses Ketamine slowly, because it is thought that a rapid infusion has the potential of both laryngospasm and emergence reactions. In the rare case where laryngospasm does occur, providers are to use a Bag-Valve-Mask (BVM), to administer positive pressure Oxygen to the patient in order to attempt to reopen the vocal cords. It is also thought that the presence of pure oxygen in the airway will relax the vocal cords allowing them to reopen, and the patient to continue breathing on their own. If these methods fail, small doses of Versed to relax the patient are also indicated, however this is considered a secondary method due to the occurrence of apnea after administration of Versed with Ketamine.

Less severe side effects, also known as adverse reactions of Ketamine are observed more frequently, usually in younger populations receiving Ketamine and those sedated with high dose Ketamine. These adverse reactions include hyper-salivation (increased oral secretions), requiring minimal oxygen to support SpO2 of >94%, and a full disassociation of a full conscious patient. These are all deemed less severe because they pose little to no harm to the patient condition or safety, and are also easily controlled by the paramedic during transport. In the case of hyper-salivation, the provider is able to suction the secretions out of the airway, and if the salivation is in copious amounts the provider is also able to administer Atropine which will stop the secretions. Further, in the cases where SpO2 drops under 94% on room air, it is considered routine patient care to administer oxygen and titrate to an appropriate level and corresponding SpO2.

The study completed by Scaggs et al. (2016) high dose Ketamine was a focus and what was thought to be routine care with this dose in administering Versed in conjunction. This proved to be a problem, when a high rate of these patients were experiencing depressed respiratory drive or apnea. As a result, for this study the conclusion of Versed increasing the likelihood of potentially severe reactions, Versed was withheld from further administrations unless needed specifically to calm an emergence reaction.

@FOAMfrat did a review on ketamine dosing with Peter Antevy linked here.

Off-label Use and Broadened Use of Ketamine

With the new research about Ketamine’s current usage, new methods of treatment are starting to be discovered. Ketamine has a known off-label use and effect of bronchodilation, however in certain cases, such as severe asthma this could be a beneficial side effect, when traditional and routine treatments are not working to help the patient. Further with severe asthmatics, in extreme cases, the patients will undergo RSI. When providers utilize Ketamine as an induction agent in RSI, the patient will likely experience bronchodilation as well as maintaining their ability to breathe on their own. RSI, is a last stitch effort in attempting to safe and control the airway of severe asthmatics. In traditional RSI induction agents, the patient will likely experience apnea, or the loss of spontaneous respiration, leading to hypoxia and the risk of anoxic brain injury. When Ketamine is used instead this will be beneficial to the patient in the long run.

Ketamine also has a side effect of increasing blood pressure and increasing heart rate. When Ketamine is given in the setting of major trauma, what is considered to be an “adverse side effect” of increasing blood pressure and heart rate could prove to be potentially lifesaving. When a patient undergoes major trauma or blood loss, a decrease in blood pressure and heart rate will drop to a life threatening level where vital organs would not be receiving adequate blood and oxygen supply. Although Ketamine in this case is not a first line medication, using it early on in trauma along with traditional means of resuscitation in these patients could be beneficial in the long-term outcome of the patient depending on the severity of the trauma endured.

Is Ketamine Safe For Head Bleeds?

Yes! In the setting  of traumatic brain injury (TBI), Ketamine administration to 156 patients did not endure an increase in ICP (Zeiler et al. 2014). Zeiler et al.  (2014) also proved Ketamine to be beneficial in multiple patients, including the incident of a patient no longer needing vasopressors to maintain hemodynamic stability. Ketamine in these patients could prove to be beneficial for the same reasons in RSI and asthmatics, where hypoxia would worsen the patient’s outcome in the long term.

Education on Use of Ketamine

Limited education and the unavoidable human error have also played a role in Ketamine’s limited use in the prehospital environment. In a study surveying currently licensed Paramedics in the United States on their education and use of Ketamine, only 53% of NR-P’s where given formal education on ketamine in their initial schooling (Buckland et al. 2017). However, 23% of NR-P’s received training through their sponsored hospital or employing company, and 33% received training on the medication as part of their department training (Buckland et al. 2017). With the lack of training regarding this medication, 44% of NR-P’s who responded to this study had researched the medication and usage on their own when education was not provided (Buckland et al. 2017).  Of the total paramedics (10,737) polled in this study, 94% reported that they feel comfortable administering Ketamine (Buckland et al. 2017). Where 96% of the paramedics reported that they were comfortable and would utilize the medication in a similar situation if presented again (Buckland et al. 2017).  

Despite the limited education provided initially and throughout many paramedic’s careers, the success rate with those who do utilize Ketamine in their practice still remains very high. This speaks to Ketamine’s large safety profile, that even when it is administered in an unpredictable environment, with the added element of human error there is a very rare occurrence of severe side effects that could pose harm to those being administered Ketamine.

Limitations

All of the research considered have strengths and limitations that have to be taken into account while forming a final conclusion about Ketamine usage. One limitation of the Wood (2003) study is the unspecified number of cases this study looked at. However, given all the cases they did review, they still were able to come to the conclusion that although there are no perfect anesthetic or analgesic agents, Ketamine comes the closest to perfect compared to the traditional anesthetic agents (Wood 2003).

Although Ketamine is an effective drug, the  Buckland et al. (2017) study, shows that the lack of education and possibly the human error can pose as a problem in the administration of prehospital Ketamine. However, many paramedics have sought information and education themselves about Ketamine prior to being able to use it in the field.  Despite the minimal education standards on Ketamine , of the paramedics polled 96% of them that used Ketamine in their practice where comfortable in its use and administration. With those who did administer Ketamine also had a 94% success rate in achieving the intended outcome with only 6% of patients who had adverse side effects or required secondary medication. Similarly of the 51% of paramedics in the Level 1 Trauma Center whose narcotics administrations were pulled for data had utilized Ketamine in their practice as well. All of these administrations had also achieved the intended outcome without severe adverse side effects. Furthermore, in the Wood (2003) study shows the human error in the accidental overdose that had occurred within the hospital. This error, is practically unavoidable in the healthcare field regardless of where providers are practicing.

Another limitation found in the Buckland et al. (2017) study was having to take in to account the biases of the Paramedics who had responded. Further, the responses had come from varying subsets of emergency medicine, rural, urban, aeromedical, fire department based as well as non-transport agencies. All of the different types of agencies, will have different amounts of emergencies they are subjected to. For example, urban agencies will come in contact with more incidents requiring chemical restraint in certain areas of the country. Where aeromedical agencies, who have larger scopes of practice than ground paramedics. They will also have more baseline training, many of the patient contacts that occur are hospital to hospital where ketamine is used more frequently and with above average education on the medication. And although this study did not specifically comment on the efficacy, it does state that per the paramedics polled, they reported Ketamine being safe and effective when needed and used, supporting the hypothesis (Buckland et al. 2017).

Further, limitations of the Level 1 Trauma Center Data Collection and Analysis (2018), the data included is a relatively small amount of data and only covers 1 year.  Additionally, during this time frame, the reporting scheme was altered in the last three months. This update modified the category of “other”, where Ketamine had to be typed in as the drug being used, to become a drop down choice. Thus,  Patient Care Report programing search only recently including Ketamine as  “dropdown choice” for  an intervention of care , may have led  to lost data. 

In both the Level 1 Trauma Center data collected and the  Scaggs  et al. (2016) study, chemical restraint was a main focus. Chemical restraint was administered as Ketamine in a high dose to sedate those patients who were deemed a threat to self and crew members. In these incidences, not administering a chemical restraint would pose more of a risk to both the patient and crews, than not administering any medication. Where if traditional chemical restraint, the patient would likely achieve the same level of sedation, however the patient would have airway and respiratory compromise as well as hemodynamic instability needed to be corrected by the paramedic rendering care in the prehospital environment. Further, there would be a longer delay in scene and crew safety due to the onset of traditional sedation medications (Versed and Ativan). When these patients were chemically restrained and sedated with Ketamine, very few had adverse or unsuccessful sedations. 

Conclusion

Following the identification of limitations and supports in Ketamine’s research in the prehospital setting, an overall consensus has been formed. Ketamine is safe, and effective when administered in its current guidelines for Paramedics. Further there is also the potential for Ketamine to be beneficial in a broader use outside the scope of practice of a Paramedic. A full consensus cannot be formed at this time about the broadened use in the prehospital setting due to a lack of available research on this part of the topic. Although there is research that proves that Ketamine is beneficial in its off-label uses, there is no current studies of its off-label use in the prehospital setting and only for care rendered in-hospital.

Further research and studies should be performed to determine a more exact range for Ketamine dose in administrations in the prehospital setting in hopes to further decrease the occurrence of laryngospasm. There should also be a baseline standard of education for all Paramedics who have completed their schooling as well as a higher standard held for those who currently utilize Ketamine in their practices. Education can be provided in the forms of in-service classes and training, and asynchronous learn on the Paramedics own time in forms of Podcasts, online classes and dedicated Continuing Medical Education (CME) for specific high-risk medications including Ketamine that paramedics are able to utilize in their practices.

Courtney Graham A.A.S, NRP, FP-C

References

Buckland DM, Crowe RP, Cash RE, Gondek S, Maluso P, Sirajuddin S, Smith ER, Dangerfield P, Shapiro G, Wanka C, et al. Ketamine in the Prehospital Environment: A National Survey of Paramedics in the United States. Prehospital and Disaster Medicine. 2017;33(01):23–28. 

Scaggs TR, Glass DM, Hutchcraft MG, Weir WB. Prehospital Ketamine is a Safe and Effective Treatment for Excited Delirium in a Community Hospital Based EMS System. Prehospital and Disaster Medicine. 2016;31(05):563–569. 

Wood P. Ketamine: prehospital and in-hospital use. Trauma. 2003;5(2):137–140. 

Zeiler FA, Teitelbaum J, West M, Gillman LM. The Ketamine Effect on ICP in Traumatic Brain Injury. Neurocritical Care. 2014;21(1):163–173. 

Kamin ,R., McClaine K, Coler R. Connecticut Statewide Emergency Medical Services Protocols. 2nd ed. 2018. 

Graham C. Unpublished data, Retrospective Analysis of a Non-Randomized, Non-Controlled, Administration of Prehospital Ketamine in a Local Urban Level 1 Trauma Center Based Ambulance. 2018.