Ketamine merits a detailed discussion because of its wide spectrum of safe uses (e.g., for sedation, regional and general anesthesia, analgesia, and psychiatry) and its availability throughout the world, even in areas with resource scarcities. (A discussion of ketamine use for Caesarian sections is in Chapter 16.)
“Ketamine is remarkably safe and is certainly the safest anesthetic if you are inexperienced.”2 Not surprisingly, in some hospitals without a trained anesthetist, up to 90% of the operations are done under ketamine.3
Ketamine is unique, producing hypnosis (sleep), analgesia (pain relief), and amnesia (short-term memory loss).4 Patients given ketamine rapidly go into a trance-like “dissociative” state, becoming detached from their surroundings. Patients’ eyes are wide open, and they have a slow nystagmus, preserve their corneal and light reflexes, and make reflexive movements.5,6 A major benefit of using ketamine is that, unless high doses are used or smaller doses are given rapidly, the patient’s airway remains open and he or she breathes spontaneously.2,5 Even if transient apnea occurs, brief bag-valve-mask (BVM) ventilation suffices until spontaneous respirations return. Another major benefit is that patients maintain their blood pressure (BP), even in shock.7 Laryngeal spasm is an extremely rare complication and can be easily treated with pressure in the “laryngospasm notch” (see Chapter 16).2
Being water and lipid soluble, ketamine can be administered intravenously (IV), intramuscularly (IM), orally, rectally, subcutaneously, transnasally, transdermally, and via an epidural block. Ketamine has a slower onset than other IV anesthetic agents after an IV bolus (1-5 minutes), and its duration of action depends on the route of administration (20-30 minutes for IM; 10-15 minutes for IV).6
Ketamine comes in three concentrations: 10 mg/mL, 50 mg/mL, and 100 mg/mL. If only one strength is to be kept in a hospital, the 50-mg/mL ampoule is the best compromise, because it can be used for IM injections or may be diluted down to 10 mg/mL for IV use. Protect the medication from light when stored. Table 17-1 lists ketamine’s physiological effects.
TABLE 17-1Ketamine’s Physiological Effects |Favorite Table|Download (.pdf) TABLE 17-1 Ketamine’s Physiological Effects
|System ||Effects |
|Cardiovascular system ||⇑ Heart rate ||⇑ BP ||⇑ CVP ||⇑ CO2 |
| ||Baroreceptors: Normal function ||Dysrhythmias: Rare || || |
|Respiratory system ||Bronchodilation ||⇑ Respiratory rate ||Preservation of airway reflexes |
|Central nervous system ||⇑ Cerebral blood flow ||⇑ Metabolic rate ||⇑ Intraocular pressure |
|Autonomic system ||Nausea and vomiting ||⇑ Salivation || |
|Genitourinary system ||⇑ Uterine tone || || || |
|Other ||Emergence delirium/dreams/hallucinations |
Do not mix barbiturates or diazepam in the same syringe or infusion as ketamine, because they are chemically incompatible. Other cerebral depressant medications prolong ketamine’s effects and delay recovery.5,8 Patients who receive repeated sedations, such as for dressing changes, often develop tolerance to ketamine and require progressively higher doses. Stop ketamine administration for 3 days to allow patients to regain their normal response.6
Ketamine has a wide variety of uses. A frequent medication for procedural sedation in medical settings (Table 17-2), ketamine is also an excellent analgesic (see Chapter 14) and antidepressant (see Chapter 38), and a drug to use during rescues, such as for an amputation on a trapped patient.5,9 The continued presence of a gag reflex under ketamine anesthesia makes operations inside the mouth problematic, although teeth can be wired for stabilization using ketamine. Bronchoscopy cannot be done under ketamine unless neuromuscular blockers are used.
TABLE 17-2Common Procedures/Surgeries Using Ketamine Sedation |Favorite Table|Download (.pdf) TABLE 17-2 Common Procedures/Surgeries Using Ketamine Sedation
|Fracture reduction ||Joint relocation ||Dressing changes |
|Abscess drainage ||Burn debridement ||Head/neck surgery |
|Dilation and curettage ||Cesarean sections ||Endoscopy |
|Foreign body removal ||Laceration repair (children) ||Cast changes |
|Radiotherapy ||Chest tube placement ||Bone marrow aspiration |
Ketamine is the ideal anesthetic for elderly, poor-risk, and dehydrated patients. It sustains rather than decreases the BP, and provides bronchodilation and decreases bronchospasm in chronic obstructive pulmonary disease (COPD) and asthma patients. For that reason, it is often used to intubate and treat patients in status asthmaticus.
Ketamine can be used as an anesthetic premedication (orally or parenterally) for anesthesia induction prior to administration of inhalational anesthetics, or for both induction and maintenance of anesthesia. It is of particular value for patients in shock, for children requiring frequent repeated anesthetic, for procedures with the patient in a prone (face-down) position that without intubation might make controlling the airway difficult, for emergency surgery when a patient has recently eaten, for surgery on patients who may be difficult to intubate, and when other anesthetics, equipment, or techniques are not available.5,8 It may also help severe asthmatic children who are unresponsive to other therapies. An optimal dose seems to be a 2- to 3-mg/kg bolus, followed by a 2- to 3-mg/kg/hr infusion.10
Anesthesia persists for up to 15 minutes after a single IV injection and is characterized by profound analgesia. (See also Chapter 14.) Ketamine also produces retrograde amnesia. Children receiving an IM injection, for example, will not recall getting the injection when they awaken.
Apnea is unusual unless ketamine is administered rapidly IV or another respiratory depressant drug, such as an opioid, is given. If only ketamine has been administered, the apnea lasts only a short time (up to 1 minute) and can easily be managed with a BVM. After a slow IV induction, breathing is well maintained and may even increase slightly.4
Airway reflexes and skeletal muscle tone are relatively well preserved, but salivary and tracheobronchial secretions increase. Despite the retention of protective reflexes, normal airway care must be maintained to prevent obstruction or aspiration.4 Laryngospasm occurs in about 1 in 500 cases after ketamine administration, although this is far less than the nearly 9 per 500 incidence with other agents.7
Ketamine stimulates the cardiovascular system, increasing the heart’s workload slightly while maintaining systemic vascular resistance. Because it does not induce hypotension, the patient does not have to remain supine. Its sympathomimetic effects are of particular value in patients who are shocked, severely dehydrated, or severely anemic.8 Ketamine raises the BP (in patients with an intact sympathetic response) by about 25% (systolic pressure increases by ~20 to 30 mm Hg) and the heart rate increases by ~20%. In the majority of patients, the BP rises steadily over 3 to 5 minutes and then returns to normal 10 to 20 minutes after injection, although there is wide individual variation that is related neither to dose nor to preexisting hypertension. Benzodiazepine premedication, such as with diazepam, reduces this rise in BP; additional small doses may control the pressure during the sedation.4 This is particularly important if ketamine must be given to patients with uncontrolled hypertension, increased intracranial pressure, thyrotoxicosis, congestive heart failure, or eclampsia.
The main problem with ketamine anesthesia is that there is no muscle relaxation. For abdominal operations or procedures on large joints (e.g., hip), a neuromuscular blocking agent and a controlled airway may be needed, requiring considerably more anesthetic prowess and eliminating one of the great benefits of using ketamine.
Preserved muscle tone may make airway control, if needed, more difficult. Unless other medications are given, the use of a laryngeal mask airway (LMA) or oral intubation will be extremely difficult.5 Ketamine does raise intraocular pressure, although only for a few minutes after administration. Eye movements may continue throughout surgery, making it unsuitable for patients with perforating eye injuries or for ophthalmic surgery where a nonmoving eye is required.4
Patients receiving ketamine may have a prolonged recovery time, sometimes accompanied by nausea and vomiting. Hallucinations can occur during recovery (although less commonly noticed in children), but they are avoided if ketamine is used solely as an induction agent and is followed by a conventional inhalational anesthetic. Their incidence may also be greatly reduced by administering diazepam both as a premedication and after the procedure.8
Ketamine is contraindicated in a number of conditions (Table 17-3). In contrast to prior dogma, it is no longer contraindicated in patients with head trauma or in children 3 to 12 months old. When relative contraindications exist, balance the need to use ketamine with the risks involved.
TABLE 17-3Contraindications to Ketamine |Favorite Table|Download (.pdf) TABLE 17-3 Contraindications to Ketamine
|Absolute Contraindications ||Relative Contraindications |
|Hypersensitivity to ketamine ||Known or suspected cardiovascular disease, including heart failure, hypertension, and angina ||Intracerebral mass, abnormality, or hemorrhage |
|Open eye procedures ||Active pulmonary infection or disease, including upper respiratory infection and asthma ||Acute porphyria |
|Age <3 months ||Major procedures stimulating posterior pharynx (e.g., endoscopy) ||History of airway instability, tracheal surgery, or tracheal stenosis |
|Liver failure ||Preeclampsia ||Glaucoma or acute globe rupture |
|Psychiatric disorders (e.g., schizophrenia, acute psychoses) ||History of cerebrovascular accident ||Thyroid disorder or taking thyroid medications |
Despite its safety record, patients should be carefully monitored during ketamine anesthesia. Secretions can cause obstruction and, although airway reflexes are usually preserved, laryngospasm and aspiration can occur. If there is no monitoring equipment, using your palm to check their breathing pattern and palpating the rate and quality of the patient’s pulse are usually sufficient.5
Judging depth of anesthesia under ketamine can be difficult, because there are few obvious signs. Spontaneous movement and eye opening may occur during adequate anesthesia, but are more common during subanesthetic doses.5
When ketamine is used for sedation, do not pretreat patients with anticholinergics. In children, premedication with benzodiazepines is unnecessary, although they should be available to treat the rare extreme emergence reaction. In adults, midazolam 0.03 mg/kg IV may be useful. Pretreating patients with odansetron may slightly reduce emesis.11
When using ketamine for anesthesia, pretreat patients to decrease salivation, either with atropine or scopolamine 20 mcg/kg (to a maximum dose of 0.5 mg [500 mcg]) given IM or IV 30 minutes before ketamine administration, or with 10 to 20 mcg/kg (to maximum 0.5 mg) of either medication given IV at the time of induction.4,13 Alternatively, glycopyrrolate, which may be a better choice due to its lower psychotropic and chronotropic effect, may be administered IV at 0.01 mg/kg (to a maximum 0.2 mg).5,6
Clonidine or diazepam may also be useful premedications before ketamine anesthesia. Oral clonidine (5 mcg/kg) reduces the hypertensive response. To reduce the dose of ketamine needed, give diazepam 0.15 mg/kg orally in adults, or promethazine 0.5 mg/kg orally in children, 1 hour prior to ketamine administration. Alternatively, give diazepam 0.1 mg/kg IV on induction.4,5 To diminish any unpleasant hallucinations and decrease muscle tone, which is particularly important in abdominal surgeries, give diazepam 0.22 mg/kg IV just before induction or orally 1 hour before induction.13 The downside is that, especially in infants, the routine administration of benzodiazepine reduces ketamine’s safety margin, and so should be avoided. A better method to prevent hallucinations is to treat patients with small doses of IV diazepam during recovery.6
Ketamine as an Anesthetic Premedication
Ketamine can be used to premedicate children before anesthesia with other agents. Oral ketamine 8 mg/kg is effective, although recovery from anesthesia is longer than normal. Intranasal ketamine can be used both as a premedicant and as an analgesic. In children, 3 mg/kg diluted to 2 mL with NS (give 1 mL per nostril) produces analgesia and sedation, but not anesthesia. (For best effect, use an atomizer. Improvised atomizers are described in Chapter 14.) This allows mask-inhalation anesthesia induction and does not cause prolonged recovery.5 Ketamine has also been used orally or rectally as a form of premedication/sedative, but its effect is unpredictable.4
Intramuscular (IM) ketamine can be used in analgesic/sedative doses or for anesthesia induction and maintenance (Table 17-4). The retrograde amnesia means that the child generally will not remember receiving the injection. IM doses last longer and wear off more slowly than do IV doses.14 When IM ketamine is used for sedation, no separate IV line is necessary.11
TABLE 17-4Intramuscular Ketamine Administration Sequence |Favorite Table|Download (.pdf) TABLE 17-4 Intramuscular Ketamine Administration Sequence
|Step ||Alternatives |
|Advance premedication || |
Atropine: 20 mcg/kg IM 30 min pre-op
Diazepam: 0.15 mg/kg orally 1 hr pre-op (adults)
Promethazine: 0.5 mg/kg orally 1 hr pre-op (children)
|Premedication at surgery || |
Atropine 10-20 mcg/kg IV prior to ketamine
|Induction ||1-2 mg/kg IV |
|Maintenance || |
IV boluses 0.5 mg/kg
IV drip 1-2 mg/min
For pediatric sedation, use 2 mg/kg IM. It takes about 5 minutes until the child is ready for the procedure.6 To induce surgical-level anesthesia, administer 5 to 10 mg/kg ketamine + 20 mcg/kg atropine, mixed in the same syringe, by deep IM injection. The child will be asleep in 3 to 5 minutes and anesthesia will last about 25 minutes.6,8 Anesthesia can be prolonged by using additional IV or IM doses of ketamine. If the IM route is used, administer additional doses of 3 to 5 mg/kg ketamine or 25% to 50% of the initial dose, as required. The need for supplementary doses is primarily determined by the patient’s moving in response to surgical stimuli.4,6,8
Ketamine’s effective dose seems to vary with a child’s nutritional status or the amount of alcohol an adult normally consumes. In malnourished children, always use less than the normal dose; in alcoholics, the dose should be higher. Experience shows that if a patient shows no signs of anesthesia after receiving three times the normal dose, a different agent should be used.4,15
If ketamine is scarce, consider giving it IV or with a neuromuscular blocker. King notes that “while 12 mg/kg IM ketamine (~840 mg for a 70-kg patient) provides an adult patient with about an hour of anesthesia; the same result comes from using about 280 mg IV. Only about half that much is needed if a muscle relaxant is used simultaneously.”16
When there is an option, administer ketamine IV, because it causes less emesis.11 The action of IV ketamine is faster than IM, but slower than other IV anesthetics. For example, within 3 to 5 minutes after an IM injection of 6 to 8 mg/kg ketamine (mixed with atropine), the patient will be ready for surgery, yet the patient should be ready in only 1 to 3 minutes following an IV injection of 1 to 2 mg/kg (mixed with atropine).9 Therefore, an IV dose of ketamine should not be given until the clinician is ready to start the procedure.
Induce a child with 1.5 to 2 mg/kg or an adult with 1.0 mg/kg ketamine by slow IV injection over 30 to 60 seconds; there appears to be no benefit to titrating it to effect with small boluses.11 More rapid administration may result in respiratory depression or apnea, as well as an enhanced pressor response. A dose of 2 mg/kg produces surgical anesthesia within 1 to 3 minutes that should last from 10 to 15 minutes.4,5,8
Maintenance anesthesia with ketamine can be achieved using IV boluses. Either give intermittent boluses of IV ketamine (0.5 mg/kg, or 50% of the original IV dose) every 15 to 20 minutes, or give boluses according to the patient’s response to surgical stimuli—pupil size, heart rate, BP, movement, and so forth.5,6,8,9 During longer procedures, the clinician should note the time interval between induction and the first supplemental dose, so that he or she can begin to inject further increments slowly at the next appropriate time.4
Maintaining anesthesia using a ketamine drip (a) allows better control of the anesthetic depth than do the IM or bolus IV methods, (b) has a rapid induction and recovery, and (c) is less likely to cause a respiratory arrest than using IV boluses.17 In circumstances in which non-anesthetists (and even nonmedical personnel) must give anesthesia, a ketamine drip permits a standardized protocol that most physicians and nurses can follow to administer anesthesia safely with minimal instruction.18
To use this method, make a ketamine solution of 1 mg/mL by dissolving 10 mL of ketamine containing 50 mg/mL in 500 mL of 5% dextrose or normal saline (0.9%, NS). For short procedures, mix smaller volumes, but keep it at 1 mg/mL for ease of administration. If the surgeon will also be giving the anesthetic (not unusual in the developing world), he or she should start the ketamine drip (using a 10 drop/mL infusion set) before beginning to scrub.
The method that King and others use for an average size adult is to start the drip at 1 to 2 drops/kg/min (non-micro drip IV chamber 15 drops/mL), which equals 1 to 2 mg/min ketamine, to maintain spontaneous ventilation. Some patients may need as much as 4 mg/min. Adjust the rate of infusion according to the depth of anesthesia achieved and required, as well as the size of the patient. “Continue the drip beyond the point at which the patient becomes unconscious, until surgical anesthesia is reached. This is easy to recognize, but difficult to describe. [The patient] develops a vacant stare, he does not respond to pain, but he still has his eyelash, corneal, and pharyngeal reflexes. Test his sensation of pain by pricking him with a pin. When surgical anesthesia has been reached, slow the drip to 60 to 80 drops/minute. This is about one drop/minute/kg body weight (4 mg/kg/hour).”19
In part, the nature of the surgery determines the required level of anesthesia, with minor procedures needing a smaller dose. The dose also depends on whether the patient has received a premedication. “If the patient is shocky, give him the smallest dose of ketamine that will keep him quiet. If he seems to react to the pain of the operation, increase the speed of the drip to 120 drops a minute. Stop operating until conditions are again satisfactory. Later, you may be able to slow the drip.”19 Generally, the ketamine will need to be discontinued 10 to 20 minutes before the end of the operation to avoid delayed emergence.4,5,6
During ketamine anesthesia, spontaneous patient movement is common, which may bother both the surgeon and the anesthetist. However, these patients are still anesthetized and the movements should not deter surgery. Surgeons and anesthetists who have experience using ketamine should be able to differentiate between spontaneous ketamine movements occurring during full ketamine anesthesia and spontaneous movements because of “lightening” of anesthesia.4
The 1:1 mixture of 10 mg/mL ketamine and 10 mg/mL propofol in a single syringe (ketofol) is commonly used around the world for pediatric sedation. With this formulation, each milliliter of solution contains 5 mg ketamine and 5 mg propofol. Titrate 0.5 mg/kg of either component drug at 30-second to 1-minute intervals to achieve the required sedation. Generally, <3.0 mg/kg (avg. 0.8 mg/kg) of each drug is used. The sedation is generally viewed as smoother than with ketamine alone and the recovery time is shorter, at <15 minutes.20
With a Neuromuscular Blockade
Ketamine infusion may be administered with a neuromuscular blockade (NMB) and intubation. This combination provides the muscle relaxation needed for abdominal and some large joint operations.
Dobson describes his procedure: “Use atropine and preoxygenate. Induce anesthesia with a fast-running ketamine infusion containing 1 mg/mL (average adult dose 50 to 100 mL). Give succinylcholine and intubate. Maintain anesthesia with ketamine 1 to 2 mg/min (more if no premedication given). After breathing returns, give a non-depolarizing relaxant. At the end of surgery, reverse muscle relaxant and extubate.”21
While the IV ketamine preparation is effective orally, a separate oral elixir is also available. Oral bioavailability is 16% to 20%, so the adult oral dose is 500 mg of ketamine plus 5 mg diazepam. For children, the oral dose is 15 mg/kg. One problem with oral administration is that the parenteral preparation tastes very bitter. Having the patient drink pure fruit juice or cola just before taking the medication or mixing the medication with juice or cola helps hide the taste. After oral administration, it takes 15 to 30 minutes to achieve sedation/anesthesia. Sedation begins earlier than anesthesia, but responses may be unpredictable and the onset may take longer.5,6
Complications with ketamine involve the airway and ventilation, gastrointestinal (GI) upset, psychiatric symptoms, unusual motor movements, and a series of relatively minor problems.
Administering ketamine too rapidly or in too large a dose can result in transient respiratory depression that may necessitate BVM or, rarely, mechanical ventilatory support.8 Excess secretions may also lead to aspiration. Though rare (~0.3% of pediatric cases), laryngospasm does occur and must be aggressively managed.13 This can be treated with constant positive pressure from a BVM or by using pressure in the “laryngospasm notch,” as described in Chapter 16.
Nausea, vomiting, and hallucinations may accompany recovery. In patients with schizophrenia, ketamine may reactivate psychoses, but there are no long-term psychiatric sequelae in nonschizophrenic patients.6
Tonic and clonic movements resembling seizures occur in some patients. These do not usually indicate a light plane of anesthesia or the need to give additional anesthetic. Although a slight increase in ketamine dose may be tried, further increases may increase the movements. At that point, benzodiazepines or analgesics may help, although this risks respiratory depression.6 Occasionally, patients under ketamine anesthesia become rigid. This can be a serious event and requires an NMB and intubation.
Other infrequent reactions include anorexia, pain and exanthems at the injection site, transient generalized erythema and morbilliform rashes, laryngospasm and other forms of airway obstruction, and transient postoperative diplopia, nystagmus, and elevated intraocular pressure.8
Return to consciousness is gradual. In contrast to the smooth induction of most anesthesia, 5% to 30% of patients may be agitated when recovering from ketamine. This occurs most often in adults, women, and those receiving large doses or rapid IV boluses.6 A state called emergence delirium, during which the patient may be disorientated, restless, and crying, sometimes occurs. The incidence of this reaction is reduced if the patient is not unnecessarily disturbed during recovery and is allowed to recover in a quiet area. However, in some tragic cases, isolating the patient has resulted in unsupervised recovery with fatal airway obstruction.
Emergence reactions are unlikely to occur if diazepam is administered preoperatively (usually diazepam 0.15 mg/kg orally 1 hour preoperatively or 0.1 mg/kg IV on induction) and supplemented, if necessary, by an additional 5 to 10 mg IV at the end of the procedure.4,8 Alternatively, promethazine can be used; this has the added advantage of an antiemetic effect. Promethazine may be given as an oral premedication (age 2 to 5 years, 15 to 20 mg by mouth [po]; 5 to 10 years, 20 to 25 mg po) or by IV at induction (25 to 50 mg IV in adults). It is not recommended for use in children <2 years old due to the risk of severe respiratory depression.6 Haloperidol can also be used to treat these reactions.22 Patients may continue to experience unpleasant dreams up to 24 hours after ketamine administration.4
Because delayed serious adverse events after ketamine sedation have not been reported, there is no reason to require that a child return to pretreatment levels of verbalization, awareness, and purposeful neuromuscular activity before discharge. In addition, requiring a child to tolerate oral fluids before discharge might unnecessarily provoke emesis. Do not wait for children to ambulate without assistance because they can experience ataxia for hours. Allow them to leave with close family observation to prevent falls.11
As a General Anesthetic in Children
In the absence of facilities for the safe administration of inhalational anesthesia, “ketamine anesthesia is considered the standard of care for children” in many developing countries.3 IM ketamine is ideal to use in children, especially those who require repeated painful procedures. Atropine can be mixed with ketamine for a single injection.5 The IM route is particularly useful in small infants prior to insertion of an IV.
Ketamine as a sole anesthetic agent is less successful in small babies, and repeated doses may lead to apnea. It is no longer recommended for sedation in children <3 months old, because they have markedly increased associated respiratory problems. If it must be used for general anesthesia in neonates, respirations can be tenuous, so always insert an airway and use a precordial stethoscope for continuous monitoring. In babies, do not use ketamine with neuromuscular blockers. Give IM atropine 15 to 30 minutes before the procedure, except in hot climates where hyperthermia may become an issue.23 In small children, anesthesia with ketamine as the sole agent for prolonged surgery may lead to delayed recovery, especially if combined with opioids.3