Ketamine for Pain and Sedation

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Introduction   

Effective sedation is crucial for managing acute pain, performing procedures, and reducing patient distress in the fast-paced hospital environment. Among the various medications used for sedation, ketamine stands out for its unique properties and versatile applications. “Ketamine remains invaluable to the fields of anesthesiology and critical care medicine, largely due to its ability to maintain cardiorespiratory stability while providing effective sedation and analgesia” [1]. 

Definition  

Ketamine is a dissociative anesthetic that induces a trance-like state, providing sedation, pain relief, and amnesia. It acts primarily by blocking N-methyl-D-aspartate (NMDA) receptors in the brain, distinct from other sedatives like benzodiazepines or opioids [1].  

History & Background  

Developed in the 1960s, ketamine was initially used in veterinary medicine before being adopted for human use.  Its rapid onset and minimal effects on respiratory function made it ideal for both battlefield and emergency medical settings. Over the decades, ketamine has gained popularity for its efficacy and safety in managing various medical procedures and traumatic injuries [1]. 

Prior to the development of Ketamine, phencyclidine, or PCP, was discovered. Researchers discovered it subdued animals and produced an intense calming effect. Higher doses of the drug were not fatal, making it an appealing option for anesthetic in humans. However, the grave side effects of extended delirium and psychosis post-anesthesia made it ultimately unviable. Researchers then went on to explore shorter-acting derivatives of PCP that would produce similar effects minus the severe post-delirium [1]. 

In 1964, two University of Michigan Professors, Dr. Edward Domino of Pharmacology and Dr. Guenter Corssen of Anesthesiology administered ketamine to human patients. The preliminary study was promising, leading the doctors to believe ketamine use in humans was safe for anesthetic purposes. After continued studies, the doctors determined that ketamine administration could not only quickly produce intense anesthesia accompanied by an unusually altered state but could also be safely readministered to maintain the anesthetic effect. It was also noted that the human patients who were administered ketamine experienced little to no side effects, furthering the promising nature of its use [1]. 

In 1970, the FDA approved Ketalar for human use. It was the first preparation of ketamine made available for human anesthesia. Ketalar was widely used in the Vietnam War due to its powerful analgesic properties and the ability to administer it without needing a full surgical suite to monitor the anesthetized patient [2].  

Ketamine is now widely used in emergency departments and ICUs nationwide with great success [1]. “Procedural sedation and analgesia (PSA) in the ED is a common practice to relieve anxiety, discomfort and pain of patients during invasive diagnosis and treatment” [3]. Ketamine use for moderate sedation allows the patient to maintain their own airway and respond to verbal commands, making it an integral part of emergency medicine [3]. 

Furthermore, ketamine provides valuable benefits compared to traditional opioid therapies in the hospital setting. It doesn’t cause respiratory depression or hypotension and has minimal effect on bowel motility. It can also be administered in several ways, including intranasally, intramuscularly, intravenously, orally, or rectally, making it a valuable option in the medical setting [4, 14]. 

Indications for Use  

In the emergency department, ketamine finds widespread use due to its rapid onset (typically within 1-5 minutes) and short duration of action (approximately 10-15 minutes) [1]. Common indications for its use include: 

• Procedural Sedation: Facilitating painful procedures such as wound repair, fracture reduction, or abscess drainage [3]. 

• Analgesia: Managing acute pain, especially in trauma patients [3]. 

• Psychiatric Emergencies: Controlling agitation and aggression, often seen in patients with severe mental health crises [1]. 

• Rapid Sequence Intubation (RSI): As an induction agent before intubation, particularly in critically ill patients [3]. 

• Direct Current Cardioversion [3] 

• Mechanical Ventilation in the ICU [4] 

Needs for ketamine use continue to grow and expand. Physicians use it for adjuvant administration with local anesthesia, low-dose anesthesia and as a new treatment for reactive airway diseases [3].  

In cases where traditional bronchodilators and corticosteroids may not provide sufficient relief, ketamine’s ability to antagonize N-methyl-D-aspartate (NMDA) receptors and inhibit glutamate transmission can help alleviate bronchospasms and airway inflammation. By reducing the hypersensitivity of the airways and modulating the inflammatory response, ketamine can potentially improve respiratory function in patients with reactive airway disease. However, its use in this context is still under investigation, and further research is necessary to establish optimal dosing and safety guidelines [5]. 

Nursing Care  

Nurses play a pivotal role in administering ketamine and monitoring patients during and after sedation. Key nursing considerations include: 

• Assessment: Conducting thorough pre-sedation assessments to evaluate patient suitability and potential risks [6]. 

• Informed Consent: Educate patients, parents or guardians about the procedure, potential side effects, and the expected recovery process, obtain a signature from patient/representative per facility policy [6]. 

• Monitoring: Vital signs, sedation level, and respiratory status must be continuously monitored throughout the procedure [6]. 

• Documentation: Nurses should ensure they accurately document the ketamine administration, patient responses, and any adverse events [6]. 

• Post-Sedation Care: Nurses should continue to monitor their patient’s vital signs to confirm they are recovering safely from sedation, assess for emergence reactions, and provide adequate pain management [6]. 

• Emergency Management: Although ketamine is well tolerated, appropriately trained nurses (ACLS, etc.) should always have emergency airway equipment and a crash cart in the procedure room and be ready to respond to airway complications or other cardiorespiratory issues that may arise [17]. 

Of very important note: The ability of nurses to administer ketamine, or any other medication, can vary significantly from state to state due to differences in state regulations, licensing requirements, and scope of practice laws. Here are some key points to consider: 

• Scope of Practice Laws: Each state has its own Nurse Practice Act (NPA) that defines the scope of practice for nurses within that state. This includes what medications nurses are allowed to administer and under what circumstances [7]. 

• Advanced Practice Nurses (APRNs): APRNs, such as nurse practitioners and clinical nurse specialists, typically have broader authority to prescribe and administer medications compared to registered nurses or licensed practical nurses [7]. 

• Certification and Training Requirements: Even if a medication like ketamine is within a nurse’s scope of practice in one state, there may be specific training or certification requirements that the nurse must meet to administer the medication [7]. 

• Collaborative Agreements: In some states, APRNs are required to have collaborative agreements with physicians in order to prescribe or administer certain medications, including ketamine [7]. 

• Setting of Administration: The regulations may also depend on the setting in which the ketamine is administered (e.g., hospital, clinic, ambulatory care, home care). Different rules may apply based on whether the setting is acute care, outpatient, or long-term care [7]. 

• Legal and Liability Considerations: States may have varying laws regarding liability and legal implications for nurses administering medications. Understanding these laws is crucial for nurses to practice safely and effectively [7]. 

Due to these variations, nurses need to be aware of and comply with the regulations in the state where they practice. They also need to stay informed about any changes or updates to these regulations that could impact their ability to administer medications like ketamine. Nurses also need to familiarize themselves with their facility’s policy regarding nurse administration of ketamine. 

Patient Safety Considerations  

While generally safe, ketamine administration requires careful attention to the following: 

• Respiratory Monitoring: Although ketamine typically preserves respiratory function, monitoring is essential, especially in patients with compromised airways or respiratory conditions [6]. 

• Hemodynamic Stability [6]: Ketamine can transiently increase heart rate and blood pressure; thus, cautious use is necessary in patients with cardiovascular disease. 

• Psychiatric Effects: Managing emergence reactions such as hallucinations or delirium, particularly in susceptible individuals [8]. 

Potential Adverse Effects of Ketamine 

Psychiatric and Cognitive Effects 

One of the most notable adverse effects of ketamine is its impact on psychiatric and cognitive functions. Ketamine is known to induce vivid hallucinations, delirium, and dissociative states, which can be distressing for patients and challenging for healthcare providers to manage. These effects may manifest as perceptual disturbances, agitation, and disorientation, particularly in patients with pre-existing psychiatric conditions or a history of substance abuse [8]. 

Furthermore, ketamine has been associated with cognitive impairment, including deficits in memory and attention span. Prolonged or repeated exposure to ketamine may exacerbate these cognitive effects, posing risks especially in vulnerable populations such as elderly patients or those with compromised neurological function [8]. 

Cardiovascular Effects 

Ketamine can significantly affect cardiovascular function, necessitating careful monitoring during administration. It has been known to cause transient hypertension and tachycardia due to its sympathomimetic properties. These cardiovascular changes are typically transient and self-limiting but can be problematic in patients with pre-existing cardiovascular disease or hypertension [9]. 

In rare cases, ketamine may also induce arrhythmias or exacerbate existing arrhythmias, highlighting the need for cardiac monitoring, particularly in patients with known cardiac risk factors [9]. 

Respiratory Effects 

Respiratory depression is another concern associated with ketamine use, albeit less common compared to other sedative agents. Ketamine’s respiratory depressant effects are typically mild and transient, characterized by a dose-dependent decrease in respiratory rate and tidal volume. However, in higher doses or in combination with other sedatives, ketamine can potentiate respiratory depression, necessitating vigilant monitoring, especially in settings where airway management may be compromised [8]. 

Gastrointestinal Effects 

Ketamine administration has been linked to an increased incidence of nausea and vomiting, particularly during the recovery phase post-sedation. Although these gastrointestinal effects are generally self-limiting, they can contribute to patient discomfort and require supportive management [8]. 

Emergence Phenomena 

Emergence phenomena such as agitation, vivid dreams, and hallucinations are common after ketamine administration, particularly during recovery. These phenomena are transient but can be distressing for patients and caregivers. Strategies to mitigate emergence phenomena include providing a calm environment, reassurance, and pharmacological interventions if necessary [8]. 

Nursing Management and Considerations: Ketamine for Agitation or Delirium 

Acute Agitation and Aggressive Behavior Management 

Ketamine is particularly indicated in situations where patients present with severe agitation, aggression, or violent behavior that poses a risk to themselves or the healthcare staff trying to treat them. This includes psychiatric emergencies such as acute psychosis, substance-induced agitation, or agitation associated with delirium secondary to medical conditions [10]. 

In emergency departments and psychiatric settings, ketamine can be administered to rapidly achieve sedation to facilitate a safe environment for further assessment and management. “New member research, published in the Annals of Emergency Medicine, shows that in ED patients with severe agitation, intramuscular ketamine provided a significantly shorter time to adequate sedation than a combination of intramuscular midazolam and haloperidol” [11]. 

Delirium Management 

Delirium, characterized by acute changes in cognition and awareness, often requires pharmacological intervention to manage symptoms and prevent complications. Ketamine’s unique pharmacodynamic profile makes it a viable option in delirious patients who do not respond adequately to conventional sedatives or in whom benzodiazepines are contraindicated due to respiratory depression concerns [12]. 

Ketamine’s ability to modulate neurotransmitter systems involved in delirium pathophysiology, such as glutamate and dopamine, may contribute to its efficacy in restoring cognitive function and reducing agitation associated with delirium. This makes ketamine a promising alternative or adjunctive therapy in the management of delirium, particularly in critically ill or postoperative patients. Studies have indicated that low-dose ketamine can be particularly helpful in reducing delirium in elderly ICU patients [12]. 

Nursing Management and Considerations: Ketamine in the Pediatric Patient  

Ketamine has emerged as a preferred agent due to its rapid onset, analgesic properties, and favorable safety profile in children.  In pediatric patients, ketamine induces a trance-like state characterized by analgesia, amnesia, and sedation, making it suitable for a variety of medical procedures [13].  

The use of ketamine and its special considerations are very similar in the pediatric population as their adult counterparts, with dosing being the main difference. 

Indications for Use in Children 

Common indications for ketamine in pediatric settings include: 

• Procedural Sedation: Facilitating painful procedures such as suturing, reduction of fractures, and lumbar punctures [13]. 

• Emergency Department Use: Managing traumatic injuries and rapid sequence intubation (RSI) in critically ill children [13]. 

• Diagnostic Imaging: Enhancing patient comfort during MRI scans or other imaging studies requiring immobility [14]. 

• Given Prior to General Anesthesia: Ketamine may be administered to children prior to GA to reduce anxiety and distress due to parental separation [15]. 

Ketamine has also been successfully used in pediatric patients with certain cardiovascular complications. “Ketamine is the general anesthetic of choice for children with congenital heart diseases with a right to left shunt, like the tetralogy of Fallot, because of its beneficial cardiovascular effects. It increases the systemic vascular resistance, decreasing the venous return and, hence, decreases the shunting of blood in the heart” [15]. Moreover, ketamine is a bronchodilator and can be used in pediatric asthma patients as a potential treatment alternative when there is no response to standard therapy [16].  

Pediatric Nursing Care Protocols 

The role of pediatric nurses in the administration and monitoring of ketamine is crucial for ensuring patient safety and procedural success: 

• Pre-Sedation Assessment: Conducting a thorough assessment to evaluate the child’s medical history, allergies, and suitability for ketamine administration [17]. 

• Informed Consent: Educating parents or guardians about the procedure, potential side effects, and the expected recovery process, signature from parent/guardian per facility policy [17]. 

• Administration and Monitoring: Ensuring accurate dosing based on weight and age, closely monitoring vital signs, level of sedation, and respiratory function throughout the procedure [17]. 

• Post-Sedation Care: Monitoring for emergence reactions, providing adequate pain management, and facilitating safe recovery in a monitored setting [17]. 

• Emergency Management: Although ketamine is well tolerated, appropriately trained nurses (ACLS, PALS, etc.) should always have emergency airway equipment and a crash cart in the procedure room and be ready to respond to airway complications or other cardiorespiratory issues that may arise [17]. 

Pediatric Safety Considerations  

While ketamine is generally well-tolerated in pediatric patients, careful attention must be paid to: 

• Respiratory Monitoring: Assessing respiratory rate, depth, and oxygen saturation continuously during and after ketamine administration [17]. 

• Cardiovascular Stability: Monitoring heart rate and blood pressure, particularly in children with pre-existing cardiac conditions [17]. 

• Emergence Delirium: Managing post-sedation delirium, hallucinations, or emergence reactions promptly and reassuring families about their transient nature. Emergence delirium is relatively uncommon in children but more widespread in adolescents [14]. 

• Adverse Effects: Recognizing potential adverse effects such as nausea, vomiting, or hypersalivation and intervening appropriately [17]. Parents/caregivers should be made aware that vomiting may occur after discharge and be offered appropriate measures for their commute home [15]. 

• Age Restriction: Ketamine is generally avoided in infants younger than three months due to airway risks in this group [18].  

Patient and Family Education  

Educating patients and families about ketamine use is crucial for informed consent and post-procedure care. When providing education to patients and families about ketamine administration, it’s important to provide information about several areas. Nurses should let the them know that ketamine is used to cause a dissociative state that allows healthcare providers to maintain comfort and safety for the patient. The medication is also intended to control anxiety and reduce any psychological symptoms the patient may be having related to the procedure. Nurses should also make patients/families aware that the lowest possible dose of medication will be used to achieve these goals, but an increase in medicine may be needed to maximize patient safety and comfort [21]. 

It’s also important to prepare parents or family members for what their loved ones may look like after medication administration. Educate them that everyone responds differently and that their family member’s vital signs and response to ketamine is being closely monitored.  

Further education should include: 

• Purpose and Use: Explain that ketamine is used as an anesthetic agent to induce loss of consciousness during surgery or medical procedures. Healthcare professionals administer it in controlled settings [17]. 

• Mechanism of Action: Describe briefly how ketamine works in the body to block certain receptors in the brain, leading to anesthesia. Use simple language to help the patient understand without overwhelming them with technical details [17]. 

• Administration: Explain the typical methods of ketamine administration, which may include intravenous (IV) injection or sometimes intramuscular (IM) injection. Emphasize that it is given by trained professionals in a hospital or surgical center [21]. 

• Expectations: Explaining the effects of ketamine, including possible sensations of dissociation or altered perception. Inform the patient about what they might experience when receiving ketamine, such as feeling disconnected from their body, having vivid dreams or hallucinations, and feeling sleepy or drowsy [13]. 

• Post-Sedation Care: Providing instructions on recovery, potential side effects, and when to seek medical help [17]. 

• Precautions and Contraindications: Highlight any conditions or medications that may interact with ketamine or make its use less safe. For example, ketamine may not be suitable for patients with certain heart conditions or a history of psychosis [21]. 

• Follow-up: Advising on follow-up appointments and medications prescribed post-procedure [21]. 

• Questions and Concerns: Encourage the patient to ask questions and address any concerns they may have about ketamine or the anesthesia process. Ensure they feel comfortable and informed before proceeding [21]. 

• Informed Consent: Finally, ensure that the patient understands the information provided and obtains their informed consent before proceeding with ketamine anesthesia. Document this consent appropriately in the patient’s medical record [6]. 

Nurses should also inform patients/families that one of the benefits of ketamine for anesthetic purposes is that it is fast-acting. As long as their post-sedation assessment deems it safe, patients can be discharged the same day they have received ketamine [14]. The patient should not drive or operate heavy machinery that day or until they feel well enough post-sedation to resume normal activities.  

By covering these topics, the nurse helps ensure that the patient has a clear understanding of ketamine anesthesia and feels more comfortable and prepared for their procedure. 

Ketamine Trends Outside of the Hospital Setting 

Ketamine’s use for depression has garnered significant interest and research attention in recent years. Ketamine is primarily used in cases where standard antidepressant treatments have not been effective. This includes patients who have tried multiple antidepressants without significant improvement in their symptoms. The rapid onset of antidepressant effects (often within hours to days) is a key advantage of ketamine over traditional antidepressants, which may take weeks to achieve noticeable results [26]. 

Ketamine for depression is typically administered intravenously (IV) or intramuscularly (IM) under medical supervision, usually in a clinic setting. The dosage and frequency of treatments vary based on individual response and treatment protocols [19]. Esketamine, however, a derivative of ketamine, has been approved by the FDA as a nasal spray for treatment-resistant depression. It is administered in a healthcare setting due to its dissociative effects and potential for misuse [26].  

It should be noted that ketamine is only approved by the FDA as an anesthetic. It has not been approved to treat any psychiatric conditions [19]. However, ketamine is still being heavily researched to treat other conditions, including alcohol abuse disorder [20], autism [22], post-traumatic stress disorder, and status epilepticus [13].  

Ketamine Abuse 

Ketamine has, unfortunately, been a drug of abuse since the 1990s. Abuse or misuse seems to be most common in the 16–24-year-old age group; however, its use in other age groups should not be discounted [23]. Ketamine is known as a party drug, and abuse and misuse are often seen at clubs or raves; however, misuse and abuse are becoming more widespread in any environment. 

Individuals who abuse or misuse ketamine may appear drunk, exceedingly calm, or stuporous if they have consumed a very high dose. They may experience hallucinations or disorientation. Acute abuse of ketamine might also be accompanied by abdominal pain, tenderness, nausea, and vomiting [23]. Due to its sedative and amnesic properties, it is also used for the nefarious purpose of facilitating sexual assault [24], which healthcare professionals should be aware of.  

“Over the last ten years, case reports have surfaced regarding young patients with recurrent cystitis. Long-term ketamine misuse can indeed lead to a sterile ulcerative cystitis” [23]. Ketamine has a caustic effect on the urothelium. Thus, chronic users may experience bladder pain, urgency, frequency, and irritation. Chronic users might also experience memory loss, cognitive deficits, and depression [23]. 

Despite ketamine’s potential for addiction, there aren’t typical withdrawal symptoms such as seen with opiates or alcohol. There have been some users who report intense cravings for the drug and physical symptoms after cessation. However, it’s thought that the continued misuse or abuse of the drug is twofold; the individual continues to use it to experience the desired pleasurable effects, and the dopaminergic sensations act as positive reinforcement of continued use [23].  

Treatment for ketamine abuse varies. Some users can seek treatment on an outpatient basis, while others will benefit from a more rigorous approach, including detox and inpatient rehabilitation. Treatment methods should be discussed between the patient and their healthcare team to determine the best route for them [25]. 

Conclusion

Ketamine is a valuable tool in the armamentarium of emergency medicine because of its rapid onset, reliable efficacy, and wide-ranging applications. While its use requires careful monitoring and consideration of individual patient factors, ketamine remains indispensable in providing safe and effective sedation in the dynamic hospital setting.  

By understanding its indications, nursing care protocols, safety considerations, and patient education needs, healthcare providers can optimize the use of ketamine to enhance patient outcomes and satisfaction in emergency care settings. 

Ketamine is now widely used to treat depression in the clinical setting despite not being approved by the FDA for this specific use. Research for ketamine use in treatment-resistant depression is ongoing. Healthcare providers should be aware that ketamine can be a drug of abuse and that there are different treatment options available. 

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