Abstract
Ketamine is a phencyclidine derivative that produces pharmacologic effects like dissociative anesthesia, sedation, catalepsy, profound somatic analgesia, amnesia, bronchodilatation, and sympathetic nervous system stimulation. It is currently being widely used as a sedative premedicant, sole or adjunct anesthetic, perioperative analgesic, sedative for procedural sedation, and analgesic cum antidepressant in pain medicine. Though ketamine has an excellent safety profile, some unique adverse effects can accompany its use. Significant complications of ketamine use include tachycardia, increase in arterial pressure, skeletal muscle hypertonia, increased salivation, laryngospasm, emergence phenomenon, nausea, and vomiting. In clinical settings, ketamine is well tolerated. Most of the complications are transient and can be managed. Ketamine-induced complications will be reduced if careful patient and surgical procedure selection with proper patient monitoring are done, the drug is administered by an anesthesiologist, the dose is lowered and titrated, and appropriate prophylactic drugs like glycopyrrolate and benzodiazepines like midazolam are administered.
Keywords
analgesia, anesthesia, emergence reaction, hemodynamic, ketamine, laryngospasm, sedation
Case Synopsis
A 22-year-old woman is posted for an emergency appendectomy. She is hemodynamically stable and administered a spinal anesthesia. The surgeon makes the abdominal incision, but on deeper dissection the patient cries out in pain. The anesthesiologist administers bolus ketamine intravenously (2 mg/kg) and asks the surgeon to go ahead. Soon after the bolus dose, there is respiratory depression and apnea for a few seconds, which recedes with intermittent positive-pressure ventilation. After some time, the surgeon complains of tightness of the abdominal muscles and inability to continue with the surgery. He demands better relaxation. The patient’s limbs are tight. She is clenching her teeth tightly, and there is a slight rise in her arterial pressure and heart rate. Oral secretions appear. She is suctioned and administered intravenous (IV) glycopyrrolate (0.02 mg/kg). Laryngospasm ensues, and the arterial oxygen saturation falls. The anesthesiologist administers IV succinylcholine 1.5 mg/kg, intubates her trachea, and maintains further muscle relaxation with IV vecuronium. She is reversed and extubated at the end of the surgery. In the recovery room, soon after shifting, she is frequently blushing, shows lip-smacking movements, is casting coy glances here and there, and is repeatedly shouting loudly, “What? What is it? Where are you?” Her cry is disturbing to all the staff and patients in the recovery area. She repeatedly tries to get up from her bed, pulls out her nasogastric tube, and has a bout of vomiting. The anesthesiologist and recovery room doctor administer IV midazolam 0.05 mg/kg and IV ondansetron (0.15 mg/kg). Her agitation soon decreases.
Problem Analysis
Definition
Ketamine is a phencyclidine derivative that produces pharmacologic effects such as dissociative anesthesia, sedation, catalepsy, profound somatic analgesia, amnesia, bronchodilation, and sympathetic nervous system stimulation. It is currently being widely used as a sedative premedicant, sole anesthetic or adjunct anesthetic, perioperative analgesic, sedative for procedural sedation, and an analgesic cum antidepressant in pain medicine. Though ketamine has an excellent safety profile, some unique adverse effects can cause complications during its use ( Table 89.1 ).
| Intraoperative/During the Infusion | Postoperative/After Discontinuing Infusion | After Prolonged and Repeated/Recreational Use |
|---|---|---|
| Increase in arterial pressure and heart rate | Emergence phenomenon | Hemorrhagic cystitis, hydronephrosis, papillary necrosis |
| Increase in oral and tracheobronchial secretions, laryngospasm, airway obstruction | Nausea and vomiting | Abdominal cramps (“K” cramps) Mild transient increase in liver enzymes |
| Increase in skeletal muscle tone (opisthotonus, bizarre postures, clonus), purposeless movements | Neurocognitive impairment, memory and attention deficits, emotional blunting, impaired language skills | |
| Slight rise in ICP and IOP, seizures, nystagmus, transient diplopia | Tolerance | |
| Withdrawal syndrome with psychosis after discontinuation, dependence | ||
| Transient apnea, respiratory depression, hiccups | ||
| Negative cardiovascular (direct cardiac depressant) effects in critically ill and severely stressed patients/with high-dose ketamine |
Recognition
The case synopsis illustrates significant complications of ketamine use: (1) tachycardia and increase in arterial pressure, (2) skeletal muscle hypertonia, (3) increased salivation, (4) laryngospasm, (5) emergence phenomenon, and (6) nausea and vomiting.
Tachycardia and Increase in Arterial Pressure
Ketamine administration leads to centrally mediated increase in sympathetic tone and release of catecholamines from the adrenal medulla, thus causing an indirect increase in the blood pressure (BP) and heart rate. The episodes of tachycardia and hypertension are short. In the absence of depressant premedication, the rise in heart rate is about 15% to 25%, and the rise in systolic pressure in adults receiving clinical doses of ketamine is about 20 to 40 mm Hg (10% to 50% above preanesthesia values) with a slightly lower rise in diastolic pressure. The BP rises steadily over 3 to 4 minutes after injection and then declines to normal limits over the next 10 to 20 minutes.
Increase in Skeletal Muscle Tone
This is most prominent after an initial IV bolus and gradually decreases.
Respiratory Depression/Apnea
This may occur due to rapid administration of a normal dose/administration of an unusually large dose and concurrent use of sedative drugs. It is transient and appears 1 to 2 minutes after rapid IV administration due to unusually high central nervous system levels. Midazolam when coadministered can increase the likelihood of apnea.
Laryngospasm
Increased salivation can lead to laryngospasm. The chances of laryngospasm are more after intramuscular (IM) ketamine administration, especially in children, in children with upper respiratory tract infection/airway anomalies/airway procedures, and in adults receiving high IM doses. The laryngospasm may be transient, but sometimes may be intractable and repetitive.
Nausea and Vomiting
It usually occurs late during the recovery phase when the patient is alert and can clear the airway without assistance.
Emergence Reactions
These are undesirable psychomimetic reactions that complicate recovery from ketamine anesthesia. They occur secondary to ketamine induced depression of auditory and visual relay nuclei, leading to misinterpretation or misperception of auditory and visual stimuli. They can be of varying severity and types. They abate within a few hours. The common clinical manifestations include agitation, pleasant and unpleasant hallucinations, confusion, euphoria, fear, disorientation, sensory and perceptual illusions, nightmares (up to 3 to 30 postoperative days), delirium, excitation, aggressive behavior, out-of-body sensation, paresthesia, short-lasting delusions, feeling of a sensation of light throughout the body, colorful vision, distorted shape and size of body parts, novel experiences concerning body consistency as made of dry wood/plastic/foam rubber, melting together with someone/environment, feeling energized and getting a strong urge to move around and talk to people, monosyllable mumble, feeling of numbness in the extremities, losing of sense of time and identity, “giggliness,” feelings of estrangement or isolation, negativism, hostility, and repetitive motor behavior. The recovery agitation is mild in 6.3% of cases and clinically important in 1.4% of cases. The differential diagnosis includes alcoholic delirium tremens, head injury–induced delirium, postoperative cognitive dysfunction/postoperative delirium/atropine-induced delirium in the elderly, and postoperative delirium due to sevoflurane/isoflurane/desflurane in children.
Risk Assessment
The hemodynamic effects are seen at anesthetic doses and are not measurable at subanesthetic doses. The increase in salivation is particularly seen in children and at higher doses. Ketamine-associated laryngospasm and respiratory depression/apnea are transient and the incidence is 0.3% and 0.8%, respectively, in children. The incidence of ketamine-induced vomiting is more in adults (5% to 15%) compared with children, and the peak age for vomiting is early adolescence. High IV doses, anesthetic doses, and the IM route are associated with a higher rate of vomiting. The incidence of emergence reactions ranges from 3% to 100% and is more and of a larger magnitude in adult patients (age >15 years and <65 years; 30% to 50%) compared with children (5% to 15%) and in women compared with men. Incidence is less after oral administration. Also, it is higher in patients with psychotism/known schizophrenia. There is a dose-effect relationship between the ketamine dose and the intensity of the psychomimetic effects. The psychomimetic effects increase at doses above 0.3 mg/kg IV bolus. Complications such as increase in intracranial pressure and intraocular pressure (IOP) may be exacerbated in the presence of hypercarbia. Nystagmus and diplopia occur at all doses of ketamine. IM/IV ketamine–associated seizures have been reported in both healthy and epileptic patients with premedication and induction doses. However, the drug has shown both proconvulsant and anticonvulsant effects.
Implications
The cardiovascular-stimulating properties of ketamine can produce an undesirable hemodynamic response to intubation; hinder intraoperative elective hypotension, especially in the first 15 minutes after ketamine administration; play havoc with the surgical field; cause life-threatening engorgement of vascular tumors of the tongue and resultant airway obstruction; and prove disastrous in patients with preexisting hypertension or cardiovascular disease/intravascular aneurysms. The skeletal muscle hypertonia produced by ketamine can make operating conditions very difficult for the surgeon, especially during intraabdominal and intrathoracic operations. The hypersalivation caused by ketamine can cause laryngospasm and airway obstruction, make taping of the endotracheal tubes difficult, and may impair visualization during fiberoptic intubation. The purposeless limb movements, muscle rigidity, rise in pulse rate and blood pressure, increased salivation, and laryngospasm are sometimes misdiagnosed as signs of light anesthesia leading to administration of high doses of ketamine, which can cause further complications. Because ketamine can sometimes disturb patency of the airway and cause vomiting, it should be avoided for procedures in the prone position and in patients with a full stomach. The increase in IOP and nystagmus make ketamine unsuitable in surgeries for glaucoma and open eye injuries. Emergence reactions can be frightening and disturbing to the patient, the anesthesiologist, the surgeon, recovery room staff, other neighboring patients, and relatives and cause damage to the surgical site and drains.
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