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InFocus: Yet Another Ketamine Myth Debunked

Roberts, James R. MD

doi: 10.1097/01.EEM.0000455721.15127.63
InFocus

Dr. Robertsis a professor of emergency medicine and toxicology at the Drexel University College of Medicine in Philadelphia. Read the Procedural Pause, a blog by Dr. Roberts and his daughter, Martha Roberts, ACNP, CEN, athttp://bit.ly/ProceduralPause, and read his past columns athttp://bit.ly/RobertsInFocus.

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Ketamine, as it turns out, is a wonderful drug that is significantly underused in the ED. Our anesthesia colleagues have kept this drug a secret for many years, often putting up objections or obstacles to its use outside the OR. Frequently quoted adverse effects have prompted many adult clinicians to eschew this drug for indications that beg for its use. Pediatricians, contrary to their normal conservative modalities, have adopted ketamine as a routine drug for sedating children undergoing painful procedures in the ED. Many adult practitioners have never used ketamine, know very little about it, and have been dissuaded from using the drug by outdated and incorrect policies and procedures, and scary warnings. Overall, however, ketamine is safer than most of the drugs used in the ED for conscious sedation.

One commonly quoted contraindication to ketamine use is that it will elevate intracranial or increased cerebral perfusion pressure, markedly raising these parameters to result in detrimental effects, particularly in patients with head trauma. This is essentially another myth about ketamine, and concerns about use of this drug in the ED by emergency physicians are unnecessary.

The Effect of Ketamine on Intracranial and Cerebral Perfusion Pressure and Health Outcomes: A Systematic Review

Cohen L, Athaide V, et al

Ann Emerg Med

Published online July 22, 2014

This study evaluated the available evidence on the effects of ketamine on intracranial and cerebral perfusion pressures, and focused on neurological outcomes, ICU length of stay, and mortality when the drug is used. This article nicely reviews the medical literature on the use of ketamine and other sedatives in intubated ICU patients. Authors reviewed 10 studies that met the inclusion criteria, reporting data on about 1,000 patients.

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These authors conclude that ketamine for managing an undifferentiated critically ill patient is safe and effective. Yet, U.S. emergency physicians have been generally reluctant to adopt it. Only three percent reported any ED intubations performed with ketamine in 2002. That number has certainly increased over the past few years. One of the reasons for the reluctance to use ketamine is based on 40-year-old data suggesting that ketamine can increase intracranial pressure. These reports were based on observations in patients with preexisting intracranial pathology, usually space-occupying lesions or obstructive hydrocephalus, and emergency clinicians rapidly adopted propofol and etomidate as substitutes in the ED, especially for undifferentiated patients.

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Of course, a high number of undifferentiated critically ill patients require emergency airway management in the ED before any investigations can be performed to rule in or rule out CNS pathology. Unknown but wildly agitated patients must be chemically restrained. These authors review the human data of the effects of IV ketamine continuous infusion or bolus-dosing in patients who had been previously intubated or who were being intubated at the time of data collection. The acceptable studies for analysis included randomized controlled trials, prospective controlled studies, and studies that included a comparison group treated with an IV drug that might also be used for rapid sequence intubation in the ED.

Interestingly, three of the five randomized controlled trials were conducted on patients with severe traumatic brain injury and a Glasgow coma scale less than 8. Other trials included critically ill patients suffering multiple trauma. Some studies enrolled patients undergoing neurosurgical intervention for a space-occupying lesion, obstructive hydrocephalus, or nontraumatic subarachnoid hemorrhage. The studies used the patients' baseline data as controls. Agents also used for comparison included fentanyl, fentanyl derivatives, and etomidate.

Eight studies examined the relationship between ketamine and other agents with respect to intracranial and cerebral perfusion pressures. Two studies evaluated the effects of prolonged ketamine infusion in ICU patients with severe traumatic brain injury post craniotomy. The data showed no difference in the mean daily intracranial or cerebral perfusion pressure in patients treated with ketamine.

The authors also reviewed previous prospective studies to determine the CNS effect of varying doses of IV ketamine with bolus of 1.5, 3, and 5 mg/kg. These studies also measured intracranial and cerebral perfusion pressure in patients with severe traumatic brain injuries. These studies as a group showed a slight decrease in intracranial pressure initially, with a slightly increased intracranial pressure after that. The elevation of intracranial pressure was minimal and clinically inconsequential between ketamine and alternative treatments. No effect was seen on cerebral perfusion pressure.

No significant difference was found among various drugs for neurologic outcome, nor was a difference seen with ketamine and other medications for ICU length of stay or mortality.

The authors said there may be a lack of power of individual reports to detect differences in the parameters studies for the quality of the studies and the number of the patients investigated. They found no evidence, however, of any sustained changes of intracranial pressure or cerebral perfusion pressure in any of the studies analyzed. Likewise, ketamine did not affect the other outcomes examined. This evaluation directly contradicts previous dogma stating that ketamine should not be used for rapid sequence intubation in patients with head injuries.

These authors conclude that ketamine is a safe and effective drug to be used in the ED when critically ill patients have not yet been ruled out as having head traumas or elevated intracranial pressure. The main determinant of a bad outcome during intubation is prolonged hypotension, however, so one should avoid using agents that may exacerbate hemodynamic instability, including opioids, propofol, or benzodiazepines. Ketamine meets all the criteria as an alternative induction agent, and appears to get the nod over even etomidate. The authors state that all available data suggest that ketamine does not adversely affect intracranial or cerebral perfusion pressures, neurologic outcome, or mortality when compared with other commonly used intravenous induction agents.

Comment: Ketamine is a dissociative anesthetic agent similar in structure to phencyclidine (PCP). It has some unique sedating properties, and provides analgesia in addition to amnestic and sedative effects. Following a bolus dose of 1-2 mg/kg IV, the time to effect is usually less than one minute with a duration of only 10-20 minutes. This increases up to 25-30 minutes following an IM injection, usually 4-5 mg/kg. This makes IV ketamine an ideal agent for intubation, reducing a dislocated shoulder, or other short procedures in adults and children.

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The effect of ketamine on various receptors in the brain is complex, but it has been shown to increase the release of catecholamines, leading to an increase in heart rate, mean arterial pressure, and cerebral blood flow. Importantly, ketamine preserves the respiratory drive while providing a quick onset of action and analgesia.

The age-old unproven cautions about ketamine are repeated in most reviews, and recommendations have not kept up with previous published studies that prove its safety and tout its use in the ED. Ketamine is an ideal agent for intubation attempts, particularly when laryngoscopy is performed on patients who are moderately sedated but not paralyzed because of concerns about a difficult airway. It is an attractive choice for patients who are hypotensive and require rapid intubation, and it has been effective and safe in infants and adults undergoing bronchoscopy. Ketamine does produce some bronchodilation by stimulating the release of catecholamines. This gives the drug potential direct bronchodilatory effects, making it an ideal induction agent in severe asthmatics. Asthmatic patients in particular can fare poorly if they are paralyzed and remain hypoxic during intubation attempts.

Another commonly held and incorrect belief about a complication of ketamine is the reemergence phenomenon. It's usually mild inconsequential, and dissipates in a short time. Patients can experience disturbing dreams as they emerge from ketamine. Dreaming may occur, but it is often pleasant. The frequency of the reemergence phenomenon and delirium can be reduced by the concomitant use of a benzodiazepine. It would not be uncommon to add a few milligrams of IV midazolam after the intubation or the procedure has been successful to decrease some emergence symptoms. Some references caution against using ketamine in patients with heart disease, severe hypertension, or known ICP elevations, but these authors believe it is an appropriate induction agent for RSI in patients with normal blood pressure or hypotension, even if the patient has suspected intracranial pressure elevation. Its beneficial use for cardioversion attests to cardiac safety.

The use of a prolonged ketamine infusion in patients with asthma or other medical conditions is even more foreign to many EPs. I have used it a number of times in intubated patients with asthma because of its bronchodilatory effect, but it is usually turned off as soon as the patient reaches the ICU. Adding small doses of ketamine post-operatively for pain control to reduce opioid use is another rapidly progressing intervention.

No dose adjustments are required for patients with renal or hepatic impairment when using ketamine clinically. The drug comes in various concentrations, including 10 mg/ml, 50 mg/ml, and 100 mg/ml. It's generally stated that the drug should be given intravenously over a minute or so, but it is frequently used in the ED for intubation as a fast-acting bolus with minimal effects. Many asthmatics who are struggling to breathe, pulling off their oxygen or bronchodilator mask, or attempting to get off the stretcher will lie back in a dazed state, continue to breathe rapidly, and allow the bronchodilator to work after receiving ketamine. An emergency or crash intubation in a deteriorating and hypoxic asthmatic now becomes an elective one when all appropriate equipment and personnel are ready.

Ketamine IM, given to the very agitated and violent patient without IV access in the anterior thigh at a dose of 4-5 mg/kg, will produce rapid sedation in about a minute without respiratory effects. This negates the need for additional doses of an ineffectual initial dose of benzodiazepines or haloperidol to calm agitation. An uncommon side effect of ketamine is increased salivation, often times interpreted as an airway emergency. Increased saliva is transient and usually controlled easily with simple suctioning. Some pediatricians in the past have given atropine with ketamine, but its use is generally not supported as routine. It is also not common for a child to vomit after coming out of ketamine sedation. Emesis, when it occurs, is usually well into the recovery period, but it can occur at home after discharge. It occurs in less than 10 percent of children and can be helped but not totally prevented with ondansetron. Patients should not be discharged until they return to their pretreatment level of verbalization and awareness and are able to walk independently. It is best to tell them not to eat for a few hours.

Ketamine will produce a cataleptic-like state. The patient is dissociated from the surrounding environment, likely from a direct action on the cortex and limbic system. The drug is known to produce glutamate blockade in the CNS by noncompetitive NMDA receptor blocker. Very shortly after the administration of ketamine, the patient passes into a trance-like state. The eyes often remain open, but the patient does not respond to voice or stimuli and has no recollection of the events. Occasionally a small amount of clonus can be observed. Upper airway reflexes remain intact and cardiovascular stability is significant, so blood pressure and pulse rate are not markedly increased. Nystagmus is not uncommon. Elimination is primarily through the urine, with some minimal hepatic metabolism.

Ketamine has numerous uses in the ED. Many clinicians use it for cardioversion, but ideal uses are also for rapid sequence intubation or for restraint of the hostile or dangerous individual, even before a cause is determined.

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