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KETAMINE battlefield analgesic

KETAMINE  battlefield analgesic

Battle Tested: Ketamine Proves its Worth on the Front Lines

by Steven Schauer, DO, RDMS, FAAEM, Andrew D. Fisher APA-C, & LTC Robert Mabry MD onApril 29, 2015

For more about Ketamine: Read Ketamine’s Troubled Past, Promising Future

http://www.epmonthly.com/features/current-features/battle-tested-ketamine-proves-its-worth-on-the-front-lines/ 

A 36-year-old soldier was injured when he stepped on a Victim Operated Improvised Explosive Device (VOIED). His injures included a right lower extremity amputation above the knee, complete degloving of the left posterior leg from the calcaneus to the ischium, shrapnel to the scrotum, and shrapnel to the left forearm. Two tourniquets per leg were required to effectively control hemorrhage. He was awake and relatively calm, with a heart rate of 130, respiratory rate 44, and palpable radial pulse. He did not complain of significant pain until the tourniquets were applied. After addressing all life-threats, an IV was initiated. To control the pain the patient was given 75 mg ketamine and 1 mg midazolam IV. He was immediately sedated and pain free. Upon arrival at the HLZ (hot landing zone – a landing zone in hostile fire), there was a delay in the arrival of the MEDEVAC. About 25 minutes after the initial dose, the patient become more aroused and complained of pain. The ketamine and midazolam were repeated with the same effects. He was handed off to the MEDEVAC team conscious, but sedated and pain free.
Ketamine’s use in the ED as a sedating agent is well established. However, ketamine use as an analgesic agent, rather than anesthetic agent, dates back to the early 1970s, when ketamine was first introduced [15]. Over the past decade, ketamine has been used as an analgesic by US Special Forces and coalition forces in the combined Iraq and Afghanistan campaigns. The need for an effective, safe, easily administered, battlefield analgesic has made ketamine a preferred agent in the combat and austere environment. Ketamine analgesia has been pushed even further forward into the hands of combat medics in the austere environment. Within just a few years, the proven safety and efficacy of ketamine has resulted in its use military-wide.
Current TCCC guidelines recommend a starting dose of 50mg IM/IN or 20mg IV/IO slow push. Most of the previous literature on its use an analgesic agent have ranged from 0.25-0.5mg/kg of ideal body weight slow push. Anecdotally, most of the untoward events (euphoria, hallucinations, etc.) appear to be infusion rate-dependent. An easy way to avoid some of the rate-dependent side-effects is to put the desired dose of ketamine into a small bag of saline and bolus it over several minutes.
The ideal analgesic agent provides adequate pain relief with a safe therapeutic margin in a wide-variety of patients. Ketamine has been safely used in all ages- from the young pediatric population to the critically-ill elderly patient [1,2]. Inadvertent overdoses of up to 100-fold the intended dose have been documented without sequelae [3].
Ketamine as an analgesic agent has proven its worth when used in combination with other drugs or when used as a solo agent. In combination with opioid medications, the addition of ketamine has an opioid-sparing effect, making it a useful agent in the hospital and prehospital settings [4-8]. A recent randomized controlled trial demonstrated a more rapid onset of analgesic effects from ketamine compared to morphine [9]. Ketamine has become a recommended analgesic agent in the combat environment in Afghanistan due to its safety profile, favorable hemodynamic characteristics in severely injured combat casualties, rapid onset and ease of use. Current Tactical Combat Casualty Care guidelines allow for its use even in the setting of eye trauma and head injuries in which the person is conscious enough to demonstrate the need for analgesia. A recent study evaluating the use of analgesic agents at the point-of-injury found no adverse events from the use of ketamine – even under the harshest conditions with minimal to no monitoring [10]. It is a recommended agent by the Wilderness Medical Society for use in remote environments [11]. Even in the hands of non-physician practitioners it appears safe [12]. Risks associated with ketamine use in the setting of head or eye trauma appear to be supported by nothing more than medical folklore [13,14]. The Regional Emergency Medical Services Council of New York City has recently begun to adopt more wide-spread use of this agent. Based on the military’s experience, ketamine’s use as an analgesic agent in the civilian environment warrants further consideration.
A key challenge with using ketamine for pain is its classification by the FDA as an anesthetic agent. Using sub-dissociative doses of ketamine for analgesia constitutes an “off-label” use of the drug. Yet drugs we use every day – such as ondansetron – are used off-label in the ED. Certainly if ED providers can safely use opioid analgesic agents, an agent with a much safer track record should be in our arsenal. For ketamine to be accepted as a potential alternative to opioid analgesics in either the civilian EMS or emergency department setting, education of physician, nursing and administrative staff may be required. Gaining a better understating of ketamine and its potential advantages as an analgesic may improve patient care and patient safety.

Steven G Schauer, DO, RDMS, FAAEM is the Medical Director at Bayne-Jones Army Community Hospital.
LTC Robert Mabry, MD is the Director of the Military Emergency Medical Services Fellowship and the Director of Trauma Care Delivery at the Department of Defense Trauma Center of Excellence at Fort Sam Houston, TX.

Photo by The U.S. Army

REFERENCES
1. Green SM, Rothrock SG, Lynch EL, et al. Intramuscular ketamine for pediatric sedation in the emergency department: safety profile in 1,022 cases. Annals of Emergency Medicine. 1998;31(6):688-697.
2. Jabre P, Combes X, Lapostolle F, et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009;374(9686):293-300.
3. Green SM, Clark R, Hostetler MA, Cohen M, Carlson D, Rothrock SG. Inadvertent ketamine overdose in children: clinical manifestations and outcome. Annals of Emergency Medicine. 1999;34(4 Pt 1):492-497.
4. Beaudoin FL, Lin C, Guan W, Merchant RC. Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial. Academic Emergency Medicine: official journal of the Society for Academic Emergency Medicine. 2014;21(11):1193-1202.
5. Ahern TL, Herring AA, Stone MB, Frazee BW. Effective analgesia with low-dose ketamine and reduced dose hydromorphone in ED patients with severe pain. The American Journal of Emergency Medicine. 2013;31(5):847-851.
6. Galinski M, Dolveck F, Combes X, et al. Management of severe acute pain in emergency settings: ketamine reduces morphine consumption. The American Journal of Emergency Medicine. 2007;25(4):385-390.
7. Sveticic G, Farzanegan F, Zmoos P, Zmoos S, Eichenberger U, Curatolo M. Is the combination of morphine with ketamine better than morphine alone for postoperative intravenous patient-controlled analgesia? Anesthesia and analgesia. 2008;106(1):287-293, table of contents.
8. Jennings PA, Cameron P, Bernard S, et al. Morphine and ketamine is superior to morphine alone for out-of-hospital trauma analgesia: a randomized controlled trial. Annals of Emergency Medicine. 2012;59(6):497-503.
9. Miller JP, Schauer SG, Ganem VJ, Bebarta VS. Low-dose ketamine vs morphine for acute pain in the ED: a randomized controlled trial. The American Journal of Emergency Medicine. 2015.
10. Schauer SG, Robinson JB, Mabry RL, Howard JT. Battlefield Analgesia: TCCC Guidelines Are Not Being Followed. Journal of Special Operations Medicine: a peer reviewed journal for SOF medical professionals. 2015;15(1):85-89.
11. Russell KW, Scaife CL, Weber DC, et al. Wilderness Medical Society practice guidelines for the treatment of acute pain in remote environments: 2014 update. Wilderness & Environmental Medicine. 2014;25(4 Suppl):S96-104.
12. Bisanzo M, Nichols K, Hammerstedt H, et al. Nurse-administered ketamine sedation in an emergency department in rural Uganda. Annals of Emergency Medicine. 2012;59(4):268-275.
13. Cohen L, Athaide V, Wickham ME, Doyle-Waters MM, Rose NG, Hohl CM. The effect of ketamine on intracranial and cerebral perfusion pressure and health outcomes: a systematic review. Annals of Emergency Medicine. 2015;65(1):43-51 e42.
14. Wadia S, Bhola R, Lorenz D, Padmanabhan P, Gross J, Stevenson M. Ketamine and intraocular pressure in children. Annals of Emergency Medicine. 2014;64(4):385-388 e381.
15. Sadove MS, Shulman M, Hatano S, Fevold N. Analgesic effects of ketamine administered in subdissociative doses. Anesthesia and analgesia. 1971;50(3):452-457.

With the increased use of ketamine by the military medics and emergency departments is it time for more wide spread use of ketamine by civilian EMS?

May 11, 2015
By Major Andrew D. Fisher, MPAS, APA, PA-C
75th Ranger Regiment, Fort Benning
Recently, ketamine has made resurgence in the areas of emergency and pre-hospital medicine, and for good reasons.

Ketamine was first developed in 1962 and is on the WHO Model List of Essential Medications.[1,2] It is commonly used for pediatric sedation in emergency or operating room settings prior to painful procedures.[3]
The safety profile and effectiveness of ketamine make it an ideal medication in the pre-hospital setting. The use of ketamine in EMS has been somewhat limited to sedation for psychosis, other behavioral health issues, and intubation.[4-7]
In 2011, the Committee on Tactical Combat Casualty Care (CoTCCC) added it to the Tactical Combat Casualty Care (TCCC) guidelines and soon after the Defense Health Board authorized it for battlefield/pre-hospital analgesia.[8,9]
Ketamine acts as an N-methyl-D-aspartate (NMDA) receptor antagonist, but also binds to the mu and kappa opioid receptors.[10]
It can be given intravenously (IV), intramuscular (IM), intranasally (IN) and by mouth (PO). Ketamine is a dissociative anesthetic with a recommended dose of 1.0-2.0 mg/kg IV. Onset is typically within 1 minute, with effective dissociation in 5-10 minutes.[3] When given IM, dose range from 3-4 mg/kg with onset between 5-20 minutes.[2,3] Above 1.5 mg/kg IV dose, there does not appear to be any deeper sedation, only longer duration.3 Ketamine also offers analgesia in sub-anesthetic doses, depending on the literature; doses may range from 0.2 mg/kg-1.0 mg/kg IV.[2,3,10,11]
The U.S. Military has successfully been using ketamine on the battlefields of Irag and Afghanistan for the past several years.
The CoTCCC recommends 20 mg IV or 50 mg IM/IN for the initial dose with multiple anecdotal reports discussing great effects.[8,12] The 75th Ranger Regiment has used ketamine since 2009 and has noted good effects and safety in a small case series with larger doses; their current protocol uses ketamine at 75 mg IV and 250-500 mg IM.[13]
With the increased use of ketamine by the military and emergency departments, is it time for more wide spread use of ketamine by civilian EMS systems? If so, should it be used instead of opioids for analgesia in the pre-hospital setting?
1. It is safe for patients in shock
Opioids often cause undesired effects in patients, especially those who are in shock.[8]
Commonly used narcotics: morphine, fentanyl, and dilaudid, can cause hypotension, bradycardia, and respiratory depression.
When in shock there is decreased blood flow to the musculoskeletal system which can negatively effect the bioavailability of medications delivered intramuscularly.[14] 
Ketamine offers instead multiple positive effects, one of which is the release of catecholamines.[10] This allows the EMS provider to treat pain without the worry of hypotension or worsening shock due to medication administration.
In addition, ketamine increases heart rate, stroke volume, and is a bronchodilator.[10] A recent study by Shackelford and colleagues, compared blood pressures in patients who received opioids versus ketamine. Initially, the morphine group had higher blood pressures but after medication administration, the ketamine group showed an increase in blood pressure, compared to morphine, which caused a drop.[15]
Ketamine’s positive effects on the cardiovascular system make it superior to opioids in the acutely injured patient.
2. Ketamine, chronic pain, and post traumatic stress disorder (PTSD)
Pain is often seen as a symptom of injury, but maybe we should view it as a disease state of the central nervous system.[16] Clifford et al. noted that neurons are not the only cells responsible for pain; glial cells can release pro-inflammatory cytokines, nitric oxide, prostaglandins, and excitatory amino acids, which can decrease the efficacy of morphine.[17]
EMT-Ps should move past thinking of pain as just a symptom of trauma and injury, and should start to consider the long-term outcomes of the patients. What are the long-term outcomes of poorly treated pain? Untreated pain can manifest itself as chronic pain, anxiety, anger, sensitivity to external stimuli, and withdrawal from interpersonal contact.[16] By treating pain early, EMT-Ps can help decrease the morbidity associated with poorly treated pain.
There is ample data that supports early pain management in an effort to reduce the incidence of PTSD symptoms.[16-21] The properties of ketamine are thought to play a role in the reduction of PTSD by blocking glutamate via NMDA receptor blockade.[16-22] As discussed above, acutely injured patients often present in shock making opioids possibly not the best medication choice. The early administration of ketamine can control pain and possibly help decrease the incidence of PTSD.
3. Ketamine’s safety profile
Unlike opioids, ketamine has a wider safety profile. Even with accidental overdoses of ketamine in pediatric patients, there were no adverse outcomes in this population.[23] There were many concerns about ketamine’s effect on intraocular pressure (IOP) and intracranial pressure (ICP). However, these were most likely overestimated, in fact, one study demonstrated a 30 percent decrease in ICP in children undergoing procedures.[3,24,25]
Conclusion: ketamine is a safe and effective analgesia
Opioids for pain management have dominated medical practice since the Civil War. Opioids are effective in many situations, but at the same time they may not be the best choice in the pre-hospital/EMS environment. As an alternative, ketamine is a safe and effective form of analgesia at doses that range from 0.2-1.0 mg/kg.
EMS protocols give a tremendous amount of responsibility to the EMT-P, as they provide critical care to severely injured patients. Ketamine is an option and maybe a better option for pain management for EMT-Ps in the pre-hospital environment.
About the author
MAJ Fisher is the  current Regimental Physician Assistant for the 75th Ranger Regiment, Fort Benning, Georgia. He has deployed seven times in support of Operation Enduring Freedom and Operation Iraqi Freedom. He is the recipient of the Purple Heart and four Bronze Star Medals, one with Valor Device. Prior to becoming a physician assistant, he worked as a paramedic for a hospital based 911 service in Indianapolis. 
I would like to thank COL Shawn Kane, MD for his valuable comments and review of the manuscript.
References
1. Schauer S, Fisher AD, Mabry RL. Battle Tested: Ketamine Proves its Worth on the Front Lines. Emergency Physicians Monthly. 2015. http://www.epmonthly.com/www.epmonthly.com/features/current-features/battle-tested-ketamine-proves-its-worth-on-the-front-lines/. Accessed May 5, 2015.
2. Best W, Bodenschatz C, Beran D. Ketamine. World Health Organization: Expert Committee on Drug Dependance; 2014; Geneva, Switzerland.
3. Green SM, Roback MG, Kennedy RM, Baruch K. Clinical Practice Guideline for Emergency Department Ketamine Dissociative Sedation: 2011 Update. Annals of Emergency Medicine. 2011;57(5):449-461.
4. Burnett AM SJ, Griffith KR, Kroeger B, Frascone RJ. The Emergency Department Experience with Prehospital Ketamine: A Case Series of 13 Patients. Prehospital Emergency Care. 2012;16(4):553-559.
5. Le Cong M, Gynther B, Hunter E, Schuller P. Ketamine sedation for patients with acute agitation and psychiatric illness requiring aeromedical retrieval. Emerg Med J. 2012;29(4):335-337.
6. Ho JD, Smith SW, Nystrom PC, et al. Successful management of excited delirium syndrome with prehospital ketamine: two case examples. Prehosp Emerg Care. 2013;17(2):274-279.
7. Sibley A, Mackenzie M, Bawden J, Anstett D, Villa-Roel C, Rowe BH. A prospective review of the use of ketamine to facilitate endotracheal intubation in the helicopter emergency medical services (HEMS) setting. Emerg Med J. 2011;28(6):521-526.
8. Butler FK, Kotwal RS, Buckenmaier III CC, et al. A Triple-Option Analgesia Plan for Tactical Combat Casualty Care: TCCC Guidelines Change 13-04. Journal of Special Operations Medicine. 2014;14(1).
9. Defense Health Board. Prehospital Use of Ketamine in Battlefield Analgesia 2012-03. In: Department of Defense; 2012.
10. Craven R. Ketamine. Anaesthesia. 2007;62:S48-S53.
11. Svenson JE, Abernathy MK. Ketamine for prehospital use: new look at an old drug. Am J Emerg Med. 2007;25(8):977-980.
12. Schauer S, Robinson JB, Mabry RL, Howard JT. Battlefield analgesia: TCCC Guidelines Are Not Being Followed. J Spec Oper Med. 2015;15(1):63-67.
13. Fisher AD, Rippee B, Shehan JH, Conklin CC, Mabry RL. Prehospital Analgesia With Ketamine for Combat Wounds: A Case Series. J Spec Oper Med. 2014;14(4):11-17.
14. Eastridge BJ, Salinas J, Wade CE, Blackbourne LH. Hypotension is 100 mm Hg on the battlefield. Am J Surg. 2011;202(4):404-408.
15. Shackelford SA, Fowler M, Schultz K, et al. Prehospital pain medication use by U.S. Forces in Afghanistan. Mil Med. 2015;180(3):304-309.
16. Buckenmaier III CC, Griffith S. Military Pain Management in 21st Century War. Military Medicine. 2010;175(7):7-12.
17. Clifford JL, Fowler M, Hansen JJ, et al. State of the science review: Advances in pain management in wounded service members over a decade at war. J Trauma Acute Care Surg. 2014;77(3 Suppl 2):S228-236.
18. Feder A, Parides MK, Murrough JW, et al. Efficacy of Intravenous Ketamine for Treatment of Chronic Post-traumatic Stress Disorder. JAMA Psychiatry. 2014:E1-E8.
19. Grieger TA, Cozza SJ, Ursano RJ, et al. Posttraumatic Stress Disorder and Depression in Battle-Injured Soldiers. American Journal of Psychiatry. 2006;163:1777-1783.
20. Holbrook TL, Galarneau MR, Dye JL, Quinn K, Dougherty AL. Morphine Use after Combat Injury in Iraq and Post-Traumatic Stress Disorder. The new england journal of medicine. 2010;362(2):110-117.
21. McGhee LL, Maani CV, Garza TH, Gaylord KM, Black IH. The correlation between ketamine and posttraumatic stress disorder in burned service members. The Journal of TRAUMA Injury, Infection, and Critical Care. 2008;64:S195-S198.
22. Rothbaum BO, Kearns MC, Price M, et al. Early intervention may prevent the development of posttraumatic stress disorder: a randomized pilot civilian study with modified prolonged exposure. Biol Psychiatry. 2012;72(11):957-963.
23. Green SM, Clark R, Hostetler MA, Cohen M, Carlson D, Rothrock SG. Inadvertent Ketamine Overdose in Children: Clinical Manifestations and Outcomes. Annals of Emergency Medicine. 1999;34(4):492-497.
24. Bar-Joseph G, Guilburd Y, Tamir A, Guilburd JN. Effectiveness of ketamine in decreasing intracranial pressure in children with intracranial hypertension. The Journal of Neurosurgery: Pediatrics. 2009;4:40-46.
25. Drayna P, Estrada CW, Saville BR, Arnold D. Ketamine is not associated with elevation of intraocular pressure during procedural sedation. American Journal of Emergency Medicine. 2012;30(7).

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  5. Pharmacology

Ketamine Considerations for Prehospital Use


At 3 a.m. you're toned out to a single vehicle accident with one passenger who slid off the road and wrapped his car around a light pole. A 44-year-old male is alert, rates his pain a 13 on a 1–10 scale, and reports he has asthma. Vital signs include a heart rate of 70, blood pressure of 90/60, and a respiration rate of 25. Extrication will be at least 30 minutes and the patient has multiple fractures. What drug will you consider that can manage this patient's pain, improve his cardiovascular state, and sedate him for extrication? Have you considered ketamine?

History

For 63 years ketamine has been administered across a spectrum of medical practices; from veterinary and human operating theaters to battlefield hospitals, EDs and now EMS. Its short-term usages that are of interest to EMS range from mild pain control and chemical restraint to complete sedation. From a prehospital standpoint, ketamine is easy to dose and administer, relatively safe, and has an onset time appropriate to field use. Because of the many mechanisms of action and broad range of uses, ketamine may be an excellent adjunct in the field.
Synthesized in 1962, ketamine is an American pharmaceutical created by scientist Calvin Stevens, PhD, to be an anesthetic for operating room use. Its primary mechanism of action is N-methyl-D-aspartate (NMDA) receptor blockade (antagonism) for anesthesia. However, ketamine dissociates (i.e., the drug molecule breaks apart and attaches to various receptors) and affects many different receptors such as opioid channels, L-type calcium channels, nicotinic acetyl-choline ion channels, and hyperpolarisation-activated cyclic nucleotide channels (HCN1).1–3

Pharmacology, Administration & Dosage

The primary mechanism of action that is of interest to EMS is the dissociative anesthesia, which consists of three parts: analgesia, amnesia and hypnosis.2 Ketamine may be used in both pediatrics and adults for pain control, psychiatric emergencies, and complete sedation with or without intubation. Because ketamine both enhances the sensitivity of opioid receptors through NMDA antagonism and binds to kappa and mu opioid receptors, it's an effective adjunct for pain. It may be used alone or in combination with an opioid.2–4
Ketamine can be administered via IV, intramuscularly (IM), intraosseously (IO), orally, rectally or via intranasal spray.3 Dosage is weight-based and can be adjusted based on desired effect of the drug.3–6 (See Table 1, below.) The elimination half-life is approximately 180 minutes; however, sedation anesthesia begins to wear off in 10–15 minutes2,5,6 so it may have to be continuously infused via a drip or bolus as needed. Fast injection of ketamine can result in transient apnea, so the drug must be administered slowly over a minute. Ketamine and benzodiazepines must not be mixed in the same bag or syringe for a continuous infusion as precipitates can form.5,6

Airway, Sedation & Intubation

Ketamine doesn't cause respiratory depression and may decrease bronchospasm.7,8 This property makes it possible to consider deep sedation without intubation, provided the airway is stable. Consider the patient involved in a trauma or mass casualty situation with multiple fractures who requires a prolonged extrication. Ketamine administration would allow for pain control, making extrication easier on both patient and provider, while preventing or delaying an intubation. Although the airway always requires monitoring, intubation isn't necessarily required if the airway is stable—even under sedation. In an event where rapid sequence intubation or deep sedation is required, ketamine can be used as a single agent or in conjunction with a benzodiazepine when laryngeal reflex is still present.7,8

It should be noted that ketamine isn't a paralytic. An asthmatic patient who's refractory to standard treatments and who will require intubation may be more successfully intubated with ketamine because it's not a paralytic agent and does have catecholamine-stimulating properties.7 Ketamine does have the potential to induce hypersalivation, which can be managed with suction or low-dose atropine.8,9

Pain

With increasing concerns over opioid addiction, ketamine is an alternative for pain management. It can be used alone or in conjunction with a smaller dose of opioid for more effective pain control.8,10
There are some injuries where pain is so severe opioids are ineffective or would have to be given in high enough doses to cause respiratory suppression. Burns, multiple fractures, abscess drainage, and mentally challenged patients of any age with overwrought responses to pain are considered excellent candidates for ketamine.8 It's appropriate to attempt opioids first and then add ketamine for synergistic therapy or, depending on mechanism of pain, go directly to ketamine. Ketamine directly affects pain by its action on the mu and kappa receptors without causing respiratory depression.2,4 Narcan (naloxone) isn't effective on ketamine.3,11–13

Cardiology, Neurology & Physiology

Catecholamines are stimulated and released by ketamine and elevate heart rate, blood pressure, and mean arterial pressure (MAP). This makes ketamine an appropriate consideration for patients in shock or experiencing profound hypotension. Further, the increased release of catecholamines may improve myocardial contractility.
In the past, one of the concerns about administration of ketamine was that it caused elevated intracranial pressure.7,8 Current research shows that in a head injury situation, maintaining cerebral blood flow and MAP is paramount in sustaining brain function, so the current recommendation suggests ketamine may be helpful and not harmful.2,7,8

Secondary Effects, Considerations & Contraindications

One of the effects of ketamine is hallucinations, and those occur within a certain dosage range. Surgical sedation dosage is 20 times higher than the dosage required to cause hallucinations, so as the drug is eliminated, patients may go through the hallucinogenic range.2 The dosage for pain control and hallucinations are very close together. This wearing off of ketamine is called an emergence reaction and may entail a variety of mood alteration, a floating sensation, hallucination, vivid dreams, and can be pleasant or unpleasant.
Not everyone experiences the emergence reaction, but it's more common in patients over 16, women, people who dream, those who receive large doses or rapid administration.3,7 This isn't usually an issue in the field, as the ketamine won't have worn off, and hallucinations can be managed in the ED. However, if management is required, administration of a benzodiazepine, such as midazolam, is appropriate.
Ketamine may also cause increased intraocular pressure, so use with caution in patients with glaucoma or acute globe injury. Administration of ketamine can cause nystagmus or double vision. Once patients have been sedated, they may have an eyes wide open, glazed expression.
Due to the catecholamine-induced sympathetic activity, ketamine can increase myocardial oxygen demand. Continuous monitoring of the cardiac system is required. Elevations of blood pressure, heart rate, or cardiac output that become symptomatic can be treated supportively. Ethanol also inhibits NMDA function, so use with caution in an intoxicated patient.5,6,8,12
Ketamine doesn't have a reversal agent.3,13 However, the effects that are most commonly seen in ketamine use can be managed supportively or end when the drug is eliminated from the system.2
There are no absolute contraindications to ketamine administration.5 It should be used with caution or only at the advice of medical control in severely hypertensive patients, schizophrenic patients or patients experiencing hallucinations or delusions, intoxicated patients, chronic alcoholics, or pregnant patients.6Ketamine is pregnancy category C.5
Bedside counseling is very important when administering ketamine. Because of ketamine's profound induction of a hypnotic and amnestic state, patients who were awake and talking suddenly because unresponsive and dazed, and this can be extremely scary, especially for parents who are with their children.
Always be sure to explain to patients, parents and children that ketamine may cause them to not respond and look and feel funny, but that they won't feel pain or remember it.

Illicit Use

Because it's structurally similar to phencyclidine (PCP) and causes hallucinations, ketamine is a popular street drug referred to a "Special K," "K," "Kit Kat" or "Cat Valium," among others. Users experience "K-holes" or "K-land" (i.e., subjective state of dissociation from the body commonly), or "baby food" (i.e., blissful, infantile inertia). It's classified as a Schedule III controlled substance.14
If a patient has overdosed on ketamine, the signs and symptoms of OD may be sedation, hallucination, salivation, and increased heart rate, blood pressure, and decreased respirations. Treat supportively.

Wrapping it Up

Ketamine can be used in a variety of situations, possibly eliminating the need to carry multiple drugs where one would suffice. It can be used in conjunction with opioids or alone for pain control, as a single anesthetic with or without the need for intubation, and as a powerful chemical restraint in psychiatric emergencies.
Ketamine's secondary benefits include support in shock situations, increasing cardiac contractility, and cerebral perfusion.
Research is currently underway studying the uses of ketamine for long-term management of severe refractory depression and chronic pain. Early evidence suggests positive outcomes.
It's worth considering that patients who receive prehospital ketamine for sedation or pain control may experience long-term benefits that help manage pain during a prolonged healing process or depression that may accompany chronic pain.2–4,8

References

1. Domino EF. Taming the ketamine tiger. 1965. Anesthesiology. 2010;113(3):678–684.
2. Sleigh J, Harvey M, Voss L, et al. Ketamine—more mechanisms of action than just NMDA blockade. Trends in Anesthesia and Critical Care. 2014;4(2–3):76–81.
3. Annirudda P, Heining M. Ketamine. Contin Educ Anaesth Crit Care Pain. 2007;7(2): 59–63.
4. Craven R, Alkhafaji R. (June 10, 2006.) Ketamine in Anesthetic Practice. AnesthesiaUK. Retrieved Aug. 2, 2016, from www.frca.co.uk/article.aspx?articleid=100644.
5. Ketamine (RX). (n.d.) Medscape. Retrieved July 28, 2016, from http://reference.medscape.com/drug/formulary/ketalar-ketamine-343099#10.
6. Ketalar 10mg/ml Injection. (Aug. 17, 2016.) Electronic Medicine Compendium. Retrieved July 27, 2016, from www.medicines.org.uk/emc/medicine/12939/SPC.
7. Caro D. (May 11, 2016.) Induction agents for rapid sequence intubation in adults. UpToDate. Retrieved July 25, 2016, from www.uptodate.com/contents/induction-agents-for-rapid-sequence-intubation-in-adults.
8. Kurdi M, Theerth K, Deva R. Ketamine: Current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014;8(3):283–290.
9. Heinz P, Geelhoed G, Wee C, et al. Is atropine needed with ketamine sedation? A prospective, randomised, double blinded study. Emerg Med J. 2006;23(3):206–209.
10. Donnelly R. Physical compatibility and of ketamine-morphine in polypropylene syringes. Can J Hosp Pharm. 2009;62(1):28–33.
11. Mikkelsen S, Ilkjaer S, Brennum J, et al. The effect of naloxone on ketamine-induced effects on hyperalgesia and ketamine-induced side effects in humans. Anesthesiology. 1999:90(6):1539–1545.
12. Ron D, Wang J. Biology of the NMDA receptor. CRC Publishing: Boca Raton, pp. 59–70, 2009.
13. Crotty S. (2004.) Safe pediatric sedation. Ann & Robert Lurie Children's Hospital. Retrieved Aug. 8, 2016, from www2.luriechildrens.org/ce/online/article.aspx?articleID=74.
14. Drug Enforcement Agency. (August 2013.) Ketamine (street names: special k, "k", kit kat, cat valium). Drug Enforcement Agency Office of Diversion. Retrieved Aug. 8, 2016, from www.deadiversion.usdoj.gov/drug_chem_info/ketamine.pdf</

Quiz: Should you administer Ketamine?

At 0300 hrs you are toned out to a single vehicle accident with one passenger who slid off the road and wrapped his car around a light pole. The 44-year-old male is alert, rates his pain a 13 on a 1–10 scale, and reports that he has asthma. Vital signs are: heart rate 70, blood pressure 90/60 and respirations of 25. Extrication will be at least 30 minutes and the patient has multiple fractures. What drug will you consider that can manage this patient’s pain, improve his cardiovascular state and sedate him for extrication? Have you considered ketamine?
1) What makes this patient a candidate for Ketamine?
    A) Multiple fractures
    B) Prolonged extrication
    C) Shock
    D) History of asthma
    E) All of the above
2) What is Ketamine's mechanism of action?
    A) NMDA antagonism
    B) Sedation, hypnosis, analgesia
    C) Opioid potentiation
    D) Bronchodilation
    E) All of the above
3) True or False: Ketamine may help prevent bronchospasm.
4) Which is NOT an appropriate way to administer Ketamine?
    A) IM
    B) Intranasal
    C) IV
    D) Endotrachael
    E) Rectal
5) True or False: There is an antidote or reversal agent for Ketamine.
6) Ketamine increases which of the following:
    A) Respirations
    B) Heart rate
    C) Mean arterial pressure
    D) All of the above
    E) B & C
7) Which of the following is a caution to using ketamine?
    A) Schizophrenia
    B) Shock
    C) Head injury
    D) Asthma
    E) Pain
8) You decide the patient in the scenario is a candidate for sedation with ketamine. He tells you he weighs 160 lbs (~73kg). You cannot establish an IV while the patient is trapped in the vehicle, so you elect to give him IM ketamine. What dosage do you use?
    A) 2mg/kg
    B) 10 mg/kg
    C) 10 mg bolus
9) While you are waiting for the onset of the ketamine you, want explain to your patient that he may experience which of the following:
    A) Amnesia
    B) A floating sensation
    C) Vivid dreams
    D) None of the above
    E) All of the above
10) Upon sedation you note copious secretions from the patient's oropharynx. How can you manage the secretions?
    A) Emergent intubation
    B) Low dose atropine
    C) Suction
    D) B & C only
    E) All of the above 

Answers:

  1. E
  2. E
  3. True
  4. D
  5. False
  6. D
  7. A
  8. B
  9. E
  10. D

By
Ketamina en bajas dosis Para Dolor Agudo en Emergencias: Bolo IV vs Infusión Lenta
Ketamina en bajas dosis Para Dolor Agudo en Emergencias: Bolo IV vs Infusión Lenta

Dr. Ramon Reyes, MD


Bajas Dosis de Ketamina Para Dolor Agudo en Emergencias: Bolo IV vs Infusión Lenta


June 6, 2017
Introducción:

El rol de la Ketamina en el servicio de emergencia se ha expandido en los últimos años. Los usos clínicos hacen fácil entender la razón, entre éstos la analgesia, amnesia y anestesia. Sorprendentemente, la Ketamina no solo reduce el dolor agudo, sino que también disminuye el dolor crónico y neuropático. Aún más importante, ha demostrado que el uso de dosis bajas de Ketamina (0.1-0.3 mg/kg IV) puede reducir el uso de opioides. Una de las mayores dificultades que se presentan con el bolo IV a bajas dosis de Ketamina son los efectos adversos, tales como sensación de irrealidad, nauseas/vómitos y mareo. Muchos proveedores médicos de emergencias han observado una disminución de los efectos adversos cuando se administró lentamente la Ketamina. En el artículo que se revisa hoy, los autores trataron de observar si aumentando la duración del bolo IV (3-5min) de Ketamina a infusión lenta (10-15min), se podía atenuar algunos de los efectos, manteniendo la eficacia analgésica.
Lo que hicieron:
A pacientes aleatorizados presentados en el servicio de emergencias con dolor abdominal, en flanco o musculesquelético con puntuación de ≥5 al ingreso, se les dio: Ketamina 0.3mg/kg en bolo IV (aproximadamente en 5 minutos) o infusión lenta (0.3mg/kg mezclado en 100mL solución salina por 15 minutos) usando un diseño doble ciego, tipo doble simulación (Ambos grupos tuvieron bolo IV e infusión).
Metodología:
Resultado principal: Eficiencia de segura a  los 5, 15, 30, 60, 90 y 120 minutos después de la administración.
  • Escala de clasificación de efectos secundarios de anestésicos disociativos (SERSDA): Mide la severidad de nueve efectos secundarios en una escala de 0-4 para cada efecto adverso. 0 = Ausente y 4 = efecto adverso presente e irritante.
  • La escala de Sedación-Agitación de Richmond (RASS): es una escala de -4.0 – 4.0. Siendo -4= profundamente sedado, 0 = alerta y calmado, y 4 = combativo.
Resultados secundarios:
  • Eficacia Analgésica a través de la Escala Numérica de Puntuación del Dolor (NRS): una escala de 0 – 10
  • Cambios en signos vitales
  • Necesidad de analgesia de rescate
Muestra:
  • Adultos de 18-65 años que se presentaron al servicio de emergencias.
  • Principal queja siendo dolor abdominal agudo, en flanco, espalda, consecuente a un trauma en tórax o de tipo musculoesquelético.
  • Intensidad ≥5 en la escala de clasificación numérica del dolor
  • Habilidad de proveer consentimiento a tratamiento
Exclusión de Muestra:
  • Embarazo
  • Lactancia
  • Alteración del estado de consciencia
  • Alergia a Ketamina
  • Peso <46kg o="">115kg
  • Signos vitales inestables (PAS<90 o="">180mmHg, Frecuencia cardíaca <50 o="">550lpm y frecuencia respiratoria <10 o="">30rpm)
  • Antecedente de lesión en cabeza u ojo reciente
  • Convulsión
  • Hipertensión intracraneana
  • Insuficiencia renal o hepática
  • Abuso de alcohol o drogas
  • Enfermedad psiquiátrica
  • Uso de analgésicos reciente (4hrs antes)
Resultados:
  • 48 pacientes incluidos en el estudio
ResultadoBolo IV (5 min)Infusión lenta (15min)
Tasa global de sensación de irrealidad en la escala SERSDA92%54%
Pacientes con efectos adversos molestos46%17%
Pacientes sin efectos adversos molestos8%54%
  • Media de Severidad del Sentimiento de la Irrealidad con SERDSA en 5 minutos
    • IVP: 3.0
    • SI: 0.0
    • P= 0.001
  • Media escala RASS a los 5 minutos
    • IVP: -2.0
    • SI: 0.0
    • P= 0.01
  • Disminución en puntuaciones medias de dolor desde línea base a 15 minutos
    • IVP: 5.2 +/- 3.53
    • SI: 5.75 +/- 3.48
(IVP: bolo IV, SI: infusión lenta)
  • No hubo una diferencia estadística respecto a los cambios en signos vitales o en la necesidad de medicación de rescate.
  • No hubo una diferencia estadística en la escala SERSDA para 8 de las variables medidas: cefalea, fatiga, mareo, audición, visión, cambio de humor, inquietud, alucinaciones
Tasas de efectos adversos de escala SERDSA:
Efecto adversoBolo IV (5min)Infusión lenta (15min)P
Fatiga1 (4.2%)2 (8.3%)0.55
Mareo16 (66.7%)18 (75%)0.75
Cefalea4 (16.7%)4 (16.7%)1.00
Irrealidad22 (91.7%)13 (54.2%)0.008
Audición00NA
Visión6 (25%)9 (37.5%)0.53
Cambio de humor3 (12.5)2 (8.3%)0.64
Inquietud6 (25%)4 (16.7%)0.72
Alucinación2 (8.3%)3 (12.5%)0.64
Fortalezas:
  • Diseño doble ciego, tipo doble simulación: todos los participantes recibieron el placebo correspondiente con el fin de mantener a los pacientes y proveedores a ciegas.
  • Bolo IV de simulación o la infusión lenta fueron dados simultáneamente para mantener integridad del estudio.
  • Proveedores, pacientes y el equipo de investigación a cargo de la recolección de la información se mantuvieron desinformados respecto a la vía de medicación recibida
  • Sin diferencia en el dolor basal
Limitaciones:
  • Muestras a conveniencia: los pacientes no se inscribieron consecutivamente (solo de lunes a viernes 8 am – 8 pm)
  • Un solo centro de estudio
  • El pequeño tamaño de la muestra no permite la evaluación de la variación en los perfiles de seguridad de las dos vías de administración (significancia estadística) o para posibles diferencias en otra evaluación SERSDA de efectos adversos.
Discusión:
  • Si los pacientes necesitaban medicación extra para el dolor 30min después de la administración del fármaco en estudio, entonces 0.1mg/kg IV de morfina era ofrecido como analgésico de rescate.
  • Varios estudios han demostrado una correlación entre los efectos secundarios de dosis pequeñas de Ketamina con dosis rápidas de infusión. La razón farmacológica es que la lipofilia de la Ketamina le permite una rápida penetración de la barrera hematoencefálica y una rápida saturación de los receptores NMDA/glutamato.-       Exclusión de pacientes con lesión a nivel de cabeza/oído a pesar de la amplia evidencia que respalda que la Ketamina es segura en esta población
  • Los autores notaron que en su institución, 15 minutos de infusión y un bolo IV es facturado igual.
  • Una dificultad con la infusión lenta es la disponibilidad de una bomba de infusión, sin embargo los autores analizaron el colgar la infusión y mantenerla aproximadamente 15min, sin usar la bomba de infusión. Esto ahorra tanto el tiempo en ajustes de la bomba, como el problema que se vayan a acabar las bombas. Le enviamos un correo al autor principal Sergey Motov sobre esto y su respuesta fue la siguiente:
“En mi servicio de emergencias, no se usa bomba de infusión IV de manera rutinaria para infusiones corta de bajas dosis de Ketamina. Después de 6 años de hacerlo así, no ha habido mayor efecto secundario. Nuestros enfermeros y farmacéuticos están a gusto con el abordaje sin bomba al haber ajustar el flujo a un margen de tiempo de 15min. Además, limitamos la dosis máxima a 30 mg incluso si el peso de los pacientes superaba los 100kg, lo que brinda mayor seguridad/comodidad al personal. Esto solo se aplica a la infusión rápida. Para goteo continuo usamos bombas de infusión IV.
Conclusión del autor: “Bajas dosis de Ketamina dadas en infusión lenta se asocia a tasas significativamente más bajas de sensación de irrealidad y sedación, sin alguna diferencia en la eficiencia analgésica en comparación con el bolo IV.”
Relevancia clínica: Bajas dosis de Ketamina de 0.3mg/kg, mezclado en 100mL de solución salina dada en infusión lenta (15 minutos) ha disminuido el efecto adverso (alucinaciones o mareo) e igualado el perfil analgésico comparado con el bolo IV (5 minutos) de Ketamina a bajas dosis.
¿Cuál es la mejor manera de administrar bajas dosis IV de Ketamina para el dolor y minimizar efectos adversos? Respuesta:  0.3mg/kg IV de Ketamina en 100mL durante 15min (Motov S et al. AJEM 2017)
Link Original: R.E.B.E.L. EM
Autor: Salim Rezaie y Rob Bryant 
Traducción: Valeria Ordónez
Edición: Henrique Puls, MD
Bibliografía:
  1. Motov S et al. A Prospective Randomized, Double-Dummy Trial Comparing Intravenous Push Dose of Low Dose Ketamine to Short Infusion of Low Dose Ketamine for Treatment of Moderate to Severe Pain in the Emergency Department. AJEM 2017; S0735 – 6757(17): 30171 – 7.  PMID: 28283340
Para más información de este tema, visita esta revisión de Bryan Hayes en el PharmERToxGuy:
Cómo administrar baja dosis de Ketamina IV para el dolor en el Departamento de Emergencia.
Publicado por: Rob Bryant (Twitter: RobJBryant13)
https://pharmertoxguy.com/2017/03/06/how-to-administer-low-dose-iv-ketamine-for-pain-in-the-ed/



Ketamine a safer option for agitated patients and providers
Takeaways and lessons for EMS providers in the wake of one agency’s ketamine administration PR nightmare
The recent media report about the use of ketamine in restrained patients contains a few poorly drawn implications and a couple of lessons for line personnel, resulting in a public relations nightmare for the EMS agency involved.
Ketamine is a selective NMDA receptor antagonist. It induces a trance-like mental state quickly. Ketamine has also been shown to help relieve pain and maintain sedation. Unlike many narcotics, ketamine has few clinical side effects, with some patients reporting disturbing sensations when reawakening. Because of its safety profile, ketamine has been effectively used to manage violent patients who pose a risk of physical harm to themselves or to the clinicians who are trying to help them.
Top Takeaways on managing patient, provider risk
Managing violent patients is a challenge under any circumstances. Many EMS system protocols prohibit transporting patients in hand cuffs or other forms of hard restraints, and providers must resort to soft restraints to help keep a violent patient safe. Without sedation, these patients can harm to themselves, up to and including cardiac arrest in significant excited delirium. As a practitioner, I have seen patients who have broken soft restraints, dislocated shoulders and experienced serious derangements of blood pressure and heart rate.
The report provides an alternative view of these situations that, at first read, appears to paint a less flattering view of ketamine use by EMS personnel. Here are my top three takeaways from the report:
1. EMS does not blindly follow LE orders
First, it’s unlikely that EMS professionals blindly follow orders by law enforcement officers regarding a medical procedure. Clinical guidelines provide the framework for the administration of any medication in the out of hospital setting.
2. Ketamine administration is based on clinical, not criminal presentation
Second, ketamine is not administered to individuals because they are suspected of committing a crime. However, if there are stimulants or hallucinogens in the suspect’s blood stream that are causing a highly agitated state during which a crime is committed, the use of ketamine is a safe alternative to more significant, and potentially more harmful methods of control.
3. Restraints may be necessary to administer ketamine
Next, there is an implication that giving a patient ketamine after they have been restrained is somehow unwarranted. In the absence of some type of blow dart mechanism of injection, I’m not sure how else EMS providers are to administer the medication in a relatively safe manner. Hard restraints employed by law enforcement are a rapid and safe method of providing immediate control and helps to render a violent situation safer. Administering ketamine will create a safer approach to transferring a patient from the hard LE restraints to the soft restraints for EMS transport.
Moreover, the inference that somehow patients are suddenly docile or cooperative after being physically restrained is false. Patients continue to struggle, fight and resist efforts to calm down while in an agitated state. What is likely unreported is the dangerously hypertensive and tachycardia clinical state these patients are experiencing and unable to control in these situations.
What we can learn from the media portrayal of ketamine administration
There are other issues with this report. However, there are a few lessons that EMS providers should take from this article:
1.Document everything. Documentation in these situations must be extensive. I’m certain that the patient care reports provide adequate recording of the circumstances requiring ketamine administration: Why was the patient sedated?
What was the order of control?
What were the patient's observable condition and vital signs before and after restraint?
What were the reassessment findings?
What was not/could not be recorded or assessed due to the clinical presentation?
2.Maintain professionalism at all times. The increasing use of recording devices by public safety personnel increases the likelihood that comments and actions can be taken out of context. A three-second audio clip does not reflect the 45 to 60 minutes of patient contact time with violent patients. Maintain professional communication and behavior at all times, even under these highly stressful situations.
About the author
Art Hsieh, MA, NRP teaches in Northern California at the Public Safety Training Center, Santa Rosa Junior College in the Emergency Care Program. An EMS provider since 1982, Art has served as a line medic, supervisor and chief officer in the private, third service and fire-based EMS. He has directed both primary and EMS continuing education programs. Art is a textbook writer, author of "EMT Exam for Dummies," has presented at conferences nationwide and continues to provide direct patient care regularly. Art is a member of the EMS1 Editorial Advisory Board. Contact Art at Art.Hsieh@ems1.com https://www.ems1.com/ketamine/articles/384957048-Ketamine-a-safer-option-for-agitated-patients-and-providers/?NewsletterID=998922&utm_source=iContact&utm_medium=email&utm_content=Exclusives1LeftTitle&utm_campaign=EMS1Member&cub_id=[cub_id]

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