Summary Of Exposure |
A) USES: Ketamine is a drug used for the induction and maintenance of anesthesia, sedation, analgesia, and as a treatment of bronchospasm. It has also been used for the treatment of migraine headaches, depression, alcoholism, heroin addiction, and chronic pain/pain syndromes. It is a widely-used medication among veterinarians for its anesthetic and analgesic properties for small and large animals. In addition, it is a popular "club drug", used for recreational purposes. Related drugs in the same class include tiletamine and phencyclidine (PCP), however, ketamine has only 5% to 10% of the potency of pharmaceutical-grade phencyclidine. Ketamine is administered intramuscularly or intravenously when used therapeutically. When abused, ketamine is usually snorted or injected intramuscularly, however, it is occasionally used orally or intravenously. Methoxetamine, an odorless, white powder, is an arylcyclohexylamine congener of ketamine and phencyclidine (PCP). It is available from the internet and used for the dissociative and hallucinogenic properties. It may be used by oral, insufflation, intramuscular, rectal, and intravenous routes.
B) PHARMACOLOGY: Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist but also binds to opioid mu and sigma receptors at high doses. It is known as a dissociative anesthetic via its action on the cerebral cortex and limbic system and causes the release of endogenous catecholamines (epinephrine, norepinephrine). In addition, it reduces polysynaptic spinal reflexes.
C) TOXICOLOGY: At high doses, ketamine is a sigma receptor agonist, causing lethargy and coma. It is also an acetylcholine receptor agonist and GABA agonist at high doses, causing nicotinic and muscarinic effects, and sedation.
D) EPIDEMIOLOGY: Ketamine exposures are uncommon and major effects or deaths are rare.
E) WITH THERAPEUTIC USE
1) COMMON: Following usual anesthetic doses, common side effects include significant transient increases in blood pressure and heart rate, muscle rigidity, and psychomotor, psychomimetic, and acute dystonic reactions. OTHER EFFECTS: Respiratory depression, airway obstruction, and apnea are rare. Ketamine also elevates intracranial and intraocular pressures. Emergence reactions, which occur in about 12% of patients, include confusion, delirium, hallucinations, irrational behavior, and vivid dreams. These reactions are more common among adults as compared to children and the elderly.
2) WITHDRAWAL: Withdrawal can develop after chronic abuse. Manifestations include chills, autonomic arousal, lacrimation, restlessness, visual, olfactory and tactile hallucinations, nightmares, and psychological cravings.
F) WITH POISONING/EXPOSURE
1) TOXICITY: In overdose, the most common effects are sedation and respiratory depression. Other effects include dizziness, tachycardia, altered mental status, anxiety, palpitations, slurred speech, hallucinations, nystagmus, mydriasis, muscular hypertonus, trismus, psychomotor and psychomimetic reactions, emergence delirium, hypertension, and chest pain. Confusion, vomiting, and memory loss are less common. Rarely, seizures, polyneuropathy or respiratory arrest may occur but death is extremely rare following ketamine abuse. Rhabdomyolysis has been reported in patients with prolonged agitation.
2) METHOXETAMINE: Nausea, vomiting, diarrhea, perceptual distortions, dissociative/catatonic states, hallucinations, paranoia, anxiety, respiratory depression, hypertension, tachycardia, and rotatory nystagmus have been reported with methoxetamine use. A man developed agitation, a dissociative state, tachycardia, and bilateral rotary nystagmus after using methoxetamine intramuscularly (unknown quantity). His symptoms resolved gradually.
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Vital Signs |
3.3.2) RESPIRATIONS
A) Ketamine may produce respiratory depression and apnea (Reich & Silvay, 1989a; Jahangir & Rahman, 1991; Smith & Santer, 1993).
3.3.3) TEMPERATURE
A) Malignant hyperthermia has been reported in one patient (S Sweetman , 2000).
B) FEVER: CASE REPORT: A 42-year-old man who was found unconscious, presented with drowsiness, a Glasgow Coma Score (GCS) of 6/15, tachycardia (heart rate 135 beats/min), hypertension (BP 187/83 mmHg) and fever (temperature 38.2 degree C). Following supportive care, his condition improved. At this time, it was found that he drank approximately 1.5 L of beer and snorted 0.75 g of "benzofury" and 0.5 g of methoxetamine before losing consciousness. He was discharged later that day (Wood et al, 2012).
C) METHOXETAMINE WITH AMPHETAMINE: Hyperthermia (greater than 39 degrees C) developed in a 31-year-old man who had been using methoxetamine and amphetamine recreationally (Wiergowski et al, 2014).
3.3.4) BLOOD PRESSURE
A) Following usual anesthetic doses, side effects include significant transient increases in blood pressure (Anon, 1977; Becsey et al, 1972; Kaplan & Cooperman, 1971). One case of hypertension and pulmonary edema associated with intravenous ketamine in a patient with a history of cocaine/alcohol abuse has been reported (Murphy, 1993).
3.3.5) PULSE
A) Following usual anesthetic doses, side effects include significant transient increases in pulse rate and blood pressure (Anon, 1977; Becsey et al, 1972).
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Heent |
3.4.3) EYES
A) BLURRED VISION has been reported (Felser & Orban, 1982). B) LOSS OF VISION: A temporary loss of vision may be noted (Fine et al, 1974). C) INTRAOCULAR PRESSURE: A transient increase in intraocular pressure may occur (Grant, 1986). Other investigators found that intraocular pressure decreased significantly after induction, but returned to baseline following intubation and remained stable (Badrinith et al, 1986). D) MYDRIASIS was reported in 3 of 20 patients following ketamine abuse (Weiner et al, 2000). 1) METHOXETAMINE: In a study of 47 methoxetamine-related telephone enquiries to NPIS (the National Poisons Information Service in UK), stimulant-type effects (eg, tachycardia, hypertension, mydriasis, palpitation, increased sweating) were reported in 17 cases (36%; 95% CI, 24 to 50) (Hill et al, 2013).
E) NYSTAGMUS may be seen for a short time following administration of ketamine. In a retrospective review of 20 patient records of patients abusing ketamine, only 3 were reported to have nystagmus (Weiner et al, 2000). Bilateral rotary nystagmus was also seen in a patient after using methoxetamine intramuscularly (Ward et al, 2011). F) METHOXETAMINE: Rotatory nystagmus has been reported with methoxetamine use (Rosenbaum et al, 2012). 1) In a study of 47 methoxetamine-related telephone enquiries to NPIS (the National Poisons Information Service in UK), cerebellar-type effects (eg, nystagmus, tremor) were reported in 3 cases (6%; 95% CI, 2 to 17) (Hill et al, 2013).
3.4.4) EARS
A) WITH THERAPEUTIC USE 1) INTRANASAL KETAMINE: In a prospective, observational study, 40 patients (aged older than 6 years) were administered intranasal ketamine 0.5 to 0.75 mg/kg to treat pain from orthopedic injuries. Adverse effects included dizziness (n=21), feeling of unreality (n=14), nausea (n=4), fatigue (n=4), mood change (n=3), and changes in hearing (n=1) (Andolfatto et al, 2013).
3.4.5) NOSE
A) WITH POISONING/EXPOSURE 1) Epistaxis and anosmia (loss of sense of smell) have been reported following chronic snorting of ketamine (Lim, 2003).
2) In a study of acute (n=188) and chronic (n=96) toxicity of ketamine abusers (age range, 10 to 39 years) in Hong Kong, chronic nasal problems, including septal perforation were observed in 40 (42%) chronic cases (Yiu-Cheung, 2012).
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Cardiovascular |
3.5.2) CLINICAL EFFECTS
A) CATECHOLAMINE LEVEL - FINDING 1) Ketamine increases circulating catecholamine levels. 2) Transient increases in heart rate, blood pressure, systemic vascular resistance, pulmonary artery pressure and pulmonary vascular resistance have been reported in patient's breathing room air. a) CASE SERIES: Systemic vascular resistance did not increase in 16 adults who were ventilated with an FIO2 of 0.25 (Balfors et al, 1983; Reich & Silvay, 1989a).
3) Alpha and Beta blocking agents, benzodiazepines (most efficacious), and verapamil have been shown to block cardiovascular stimulation (Reich & Silvay, 1989a). 4) Cardiac dysrhythmias are rare. B) HYPERTENSIVE EPISODE 1) Patients on thyroid replacement therapy may be predisposed to developing severe hypertension and tachycardia (Kaplan & Cooperman, 1971). 2) KETAMINE: Hypertension and tachycardia have been reported in chronic oral ketamine users (Zuccoli et al, 2014). a) CASE REPORT: One case of severe hypertension and pulmonary edema associated with intravenous ketamine in a patient with cocaine/alcohol abuse has been reported (Murphy, 1993).
b) In a study of acute (n=188) and chronic (n=96) toxicity of ketamine abusers (age range, 10 to 39 years) in Hong Kong, cardiovascular effects, including hypertension (systolic blood pressure greater than 160 mmHg or diastolic pressure greater than 90 mmHg) and tachycardia (heart rate greater than 100 beats/min) were observed in 50 (27%) acute cases (Yiu-Cheung, 2012).
3) METHOXETAMINE: Hypertension and tachycardia have been reported with methoxetamine use (Hofer et al, 2012; Wood et al, 2012). a) In a study of 47 methoxetamine-related telephone enquiries to NPIS (the National Poisons Information Service in UK), stimulant-type effects (eg, tachycardia, hypertension, mydriasis, palpitation, increased sweating) were reported in 17 cases (36%; 95% CI, 24 to 50) (Hill et al, 2013).
b) A 42-year-old man who was found unconscious, presented with drowsiness, a Glasgow Coma Score (GCS) of 6/15, tachycardia (heart rate 135 beats/min), hypertension (BP 187/83 mmHg) and fever (temperature 38.2 degree C). Following supportive care, his condition improved. At this time, it was found that he drank approximately 1.5 L of beer and snorted 0.75 g of "benzofury" and 0.5 g of methoxetamine before losing consciousness. He was discharged later that day (Wood et al, 2012).
c) A 29-year-old man was found catatonic with a tremor, visual hallucinations, confusion, and dilated pupils. He presented to the ED with confusion, a GCS of 14/15, tachycardia (heart rate 121 beats/min), and hypertension (BP 201/104 mmHg). Following supportive care, his symptoms improved overnight. The next day, it was found that he drank a mixture of 200 mg of methoxetamine and water before becoming unwell (Wood et al, 2012).
d) A 28-year-old man was found unconscious with a bag of methoxetamine white powder. He later developed worsening agitation and aggression. He presented to the ED with drowsiness, a GCS of 10/15, confusion, agitation, tachycardia (heart rate 113 beats/min), hypertension (BP 198/78 mmHg), and dilated pupils. He recovered following supportive care (Wood et al, 2012).
C) TACHYCARDIA 1) KETAMINE: Hypertension and tachycardia have been reported in chronic oral ketamine users (Zuccoli et al, 2014). a) CASE SERIES/INCIDENCE: In a case series of 20 reported ketamine abusers, 12 developed tachycardia and 3 complained of palpitations (Weiner et al, 2000).
b) In a study of acute (n=188) and chronic (n=96) toxicity of ketamine abusers (age range, 10 to 39 years) in Hong Kong, cardiovascular effects, including hypertension (systolic blood pressure greater than 160 mmHg or diastolic pressure greater than 90 mmHg) and tachycardia (heart rate greater than 100 beats/min) were observed in 50 (27%) acute cases (Yiu-Cheung, 2012).
2) METHOXETAMINE: Tachycardia has been reported with methoxetamine use (Hofer et al, 2012; Rosenbaum et al, 2012). a) In a study of 47 methoxetamine-related telephone enquiries to NPIS (the National Poisons Information Service in UK), stimulant-type effects (eg, tachycardia, hypertension, mydriasis, palpitation, increased sweating) were reported in 17 cases (36%; 95% CI, 24 to 50) (Hill et al, 2013).
b) CASE REPORT: Tachycardia (105 beats/min) developed in a man who presented with agitation, a dissociative state, and bilateral rotatory nystagmus after using methoxetamine intramuscularly (unknown quantity) (Ward et al, 2011).
c) CASE REPORT: A 42-year-old man who was found unconscious, presented with drowsiness, a Glasgow Coma Score (GCS) of 6/15, tachycardia (heart rate 135 beats/min), hypertension (BP 187/83 mmHg) and fever (temperature 38.2 degree C). Following supportive care, his condition improved. At this time, it was found that he drank approximately 1.5 L of beer and snorted 0.75 g of "benzofury" and 0.5 g of methoxetamine before losing consciousness. He was discharged later that day (Wood et al, 2012).
d) CASE REPORT: A 29-year-old man was found catatonic with a tremor, visual hallucinations, confusion, and dilated pupils. He presented to the ED with confusion, a GCS of 14/15, tachycardia (heart rate 121 beats/min), and hypertension (BP 201/104 mmHg). Following supportive care, his symptoms improved overnight. The next day, it was found that he drank a mixture of 200 mg of methoxetamine and water before becoming unwell (Wood et al, 2012).
e) CASE REPORT: A 28-year-old man was found unconscious with a bag of methoxetamine white powder. He later developed worsening agitation and aggression. He presented to the ED with drowsiness, a GCS of 10/15, confusion, agitation, tachycardia (heart rate 113 beats/min), hypertension (BP 198/78 mmHg), and dilated pupils. He recovered following supportive care (Wood et al, 2012).
D) CONDUCTION DISORDER OF THE HEART 1) WITH POISONING/EXPOSURE a) METHOXETAMINE: A 21-year-old man developed an epileptic seizure and briefly lost consciousness after inhaling vapors of heated methoxetamine powder (about 50 mg) for 2 minutes. He presented to the ED conscious and oriented. An ECG revealed sinus bradycardia and ST-segment elevation in leads DII, DIII, aVF, V4 and V5, suggesting localized myocardial ischemia. Laboratory results revealed a slightly elevated creatine kinase concentration (270 Units/L) and hyponatremia (sodium 127 mmol/L). He experienced two new seizures about 5 hours after the inhalation of methoxetamine, but his symptoms resolved following supportive care and he was transferred for addiction treatment (Imbert et al, 2014).
E) CARDIAC ARREST 1) WITH POISONING/EXPOSURE a) CASE REPORT: A 69-year-old woman with a history of hypertension and asthma inadvertently received 500 mg ketamine intravenously instead of the intended dose of 50 mg IV ketamine prior to mechanical ventilation and, within minutes of ketamine administration, developed cardiopulmonary arrest and died. An autopsy showed 75% stenosis of the left anterior descending coronary artery and hypertensive heart disease. The cause of death was determined to be coronary heart disease exacerbated by ketamine overdose (Long et al, 2002).
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Respiratory |
3.6.2) CLINICAL EFFECTS
A) ACUTE RESPIRATORY INSUFFICIENCY 1) WITH THERAPEUTIC USE a) Ketamine causes a dose-related respiratory depression similar to that caused by opiates (Reich & Silvay, 1989a).
b) CASE REPORT/RESPIRATORY ARREST: A 2-year-old girl (weight 12 kg) was given ketamine 48 mg (4 mg/kg) intramuscularly for conscious sedation and developed apnea 10 minutes later (Mitchell et al, 1996). Respirations spontaneously returned after 5 to 6 artificial ventilations, and the patient was adequately oxygenated on a 100% nonrebreather face mask. The child was monitored for 3 hours and was discharged to home with no adverse sequelae reported.
2) WITH POISONING/EXPOSURE a) CASE SERIES/PEDIATRIC: In a review of 9 children who had received inadvertent ketamine overdoses during procedures performed in the ED, prolonged sedation occurred in each child along with transient respiratory depression developing in 4 of the 9 children (Green et al, 1999a). Brief mechanical ventilation was required in 2 of the 4 children. The range of exposure was 5 to 100 (1 child) times the intended dose of ketamine; the children ranged in age from 24-days to 7-years-old. 1) In one case, a 3-year-old child was to receive 8 mg (0.5 mg/kg) and inadvertently was given 800 mg (100 times the intended dose). No respiratory depression occurred; elective intubation was performed as a precaution. Despite prolonged sedation, the patient awoke 9 hours later with normal respiratory function and no alterations in mental status. The patient was discharged to home at 24 hours.
b) CASE REPORT: A 3-year-old child received 450 mg (30 mg/kg) of intramuscular ketamine instead of 45 mg during a procedure and experienced prolonged sedation (20 hours) and several episodes of airway complications (partial upper airway obstruction and a decrease in oxygen saturation to 82%), requiring repositioning of the airway and supplemental oxygen; however, intubation was not required. The child was discharged 36 hours after ketamine administration (Capape et al, 2008). c) METHOXETAMINE: Respiratory depression has been reported with methoxetamine use (Rosenbaum et al, 2012). d) METHOXETAMINE WITH AMPHETAMINE: A 31-year-old man who had been using methoxetamine and amphetamine recreationally, presented in a deep coma, with acute respiratory failure, hyperthermia (greater than 39 degrees C), and generalized seizures. Laboratory results revealed leukocytosis (WBC 50 Units x 10(3)/L), elevated serum creatinine (2.8 mg/dL), elevated liver enzymes, and signs of massive rhabdomyolysis (CPK 170,000 Units/L). An ECG revealed sinus tachycardia (HR 120 to 140 beats/min). Despite intensive supportive care, including diuresis with alkalization, Continuous Veno-Venous Hemodialysis with citrate anticoagulation, Single Pass Albumin Dialysis for hepatic failure, his condition worsened and he died after developing multi-organ dysfunction syndrome 28 days after presentation. Serum and urine analysis revealed amphetamine concentration within the non-toxic range and methoxetamine within the toxic range (0.32 mcg/mL) (Wiergowski et al, 2014). B) APNEA 1) CASE REPORT: Apnea of 45 minutes duration combined with an intense spasm of the jaw muscles occurred in a 6-year-old child after an intramuscular dose of 6 mg/kg ketamine (Jahngir & Rahman, 1991).
2) CASE REPORT: A short period of apnea has been reported in a 4-year-old child after an intramuscular dose of 4 mg/kg ketamine (Smith & Santer, 1993).
C) BRONCHIECTASIS 1) Ketamine also has bronchodilator effects, possibly related to increased catecholamine levels. Ketamine has been used for emergency intubation in patients with status asthmaticus (L'Hommedieu & Arens, 1987; Reich & Silvay, 1989a).
D) SPUTUM ABNORMAL - AMOUNT 1) Salivary and tracheobronchial secretions are increased (L'Hommedieu & Arens, 1987; Reich & Silvay, 1989a).
E) ACUTE LUNG INJURY 1) CASE REPORTS a) ADULTS 1) One case of hypertension and pulmonary edema associated with intravenous ketamine in a patient with cocaine/alcohol abuse has been reported (Murphy, 1993).
2) An 18-year-old man died after intramuscular injection of 1 gram ketamine; death was attributed to massive pulmonary edema (Licata et al, 1994).
b) PEDIATRIC 1) An 8-year-old developed fulminant pulmonary edema after receiving 125 mg ketamine IM for a dressing change of first degree burns to the hand. Within 10 minutes of administration, the child developed labored breathing, cyanosis and desaturated to 80% (while receiving 30% oxygen via ventimask; the airway was patent) requiring rapid intubation, with pink frothy fluid observed. Chest x-ray one hour later was normal and the patient was extubated 5 hours later with no further complications. The authors suggested that the possible mechanism involved in this case was the inhibition of norepinephrine uptake in postganglionic sympathetic nerve endings which resulted in elevated plasma catecholamine concentrations (Pandey et al, 2000).
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Neurologic |
3.7.2) CLINICAL EFFECTS
A) INCREASED MUSCLE TONE 1) Following usual anesthetic doses, side effects may include muscular hypertonus (Sussman, 1974). Trismus has been reported in a child (Jahangir & Rahman, 1991).
B) CENTRAL NERVOUS SYSTEM DEFICIT 1) WITH POISONING/EXPOSURE a) METHOXETAMINE: In a study of 47 methoxetamine-related telephone enquiries to NPIS (the National Poisons Information Service in UK), acute mental health disturbance-type effects (eg, agitation, confusion, euphoria, aggression, hallucination, paranoia, hysteria, and manic psychosis) were reported in 20 cases (43%; 95% CI, 30 to 57) (Hill et al, 2013).
b) KETAMINE: In one study, schizophrenia-proneness and neurocognitive function of 130 volunteers (29 cannabis (skunk) chronic users, 22 cocaine chronic users, 21 ketamine chronic users, 28 recreational poly-drug users, and 30 drug non-user controls) were evaluated. Deficits in working memory was observed only in ketamine chronic users. Ketamine and cannabis users had deficits in frontal functioning. All users had long-term memory deficits; however, this occurred mostly in the cannabis users. Affective and perceptual disturbances occurred mostly in the ketamine group; however, both cannabis and ketamine users experienced cognitive disturbances and attentional deficits (Morgan et al, 2012).
c) KETAMINE: A 2-year-old girl with an abscess requiring incision and drainage, inadvertently received 10 times the prescribed dose of ketamine (20 mg/kg of IM ketamine using a 100 mg/mL product instead of 2 mg/kg IM using a 10 mg/mL solution). She was still sedated 60 minutes after receiving ketamine. She had a normal respiratory effort, but was not arousable to verbal or tactile stimuli. Her vital signs included a blood pressure of 92/54 mmHg, pulse of 131 beats/min, and respirations of 28 breaths/min with 100% oxygen saturation on room air. Following supportive care, including 0.1 mg of glycopyrrolate for increased oral secretions, her condition returned to baseline 4 hours later and she was discharged 18 hours after receiving ketamine. Her ketamine concentrations at 97 minutes, 6 hours, and 12 hours after administration were 3800 ng/mL, 350 ng/mL, and 160 ng/mL, respectively (Thornton et al, 2015).
C) PSYCHOMOTOR AGITATION 1) WITH POISONING/EXPOSURE a) KETAMINE 1) CASE REPORT: A 34-year-old chronic oral ketamine user presented with severe agitation, anxiety, tachycardia, and hypertension. Laboratory results revealed mildly elevated liver enzymes and a positive drug urine test for ketamine and cannabis. Physical examination revealed irritability, incoherence of thought, confusion, and delusion of grandeur. He admitted to using cannabis sporadically (less than 5 times a month) and oral ketamine more than 4 times weekly. His anxiety and agitation improved significantly following supportive care, including benzodiazepine therapy (lorazepam and diazepam), but he still experienced delusions and bizarre behavior. Four days after presentation, he was started on paliperidone (6 mg/day) which resulted in a gradual improvement of his symptoms (Zuccoli et al, 2014).
b) METHOXETAMINE 1) Agitation has been reported with methoxetamine use (Hofer et al, 2012; Ward et al, 2011) .
2) CASE REPORT: A 32-year-old man developed agitation, dissociative state, tachycardia, and bilateral rotary nystagmus after using methoxetamine intramuscularly (unknown quantity). His symptoms resolved gradually in the next 8 hours (Ward et al, 2011).
3) In a study of 47 methoxetamine-related telephone enquiries to NPIS (the National Poisons Information Service in UK), acute mental health disturbance-type effects (eg, agitation, confusion, euphoria, aggression, hallucination, paranoia, hysteria, and manic psychosis) were reported in 20 cases (43%; 95% CI, 30 to 57) (Hill et al, 2013).
D) DISSOCIATIVE CONFUSION 1) WITH THERAPEUTIC USE a) METHOXETAMINE 1) Dissociative and/or catatonic states have been reported in patients using methoxetamine (Wood et al, 2012; Ward et al, 2011). a) CASE REPORT: A 32-year-old man developed agitation, a dissociative state, tachycardia, and bilateral rotary nystagmus after using methoxetamine intramuscularly (unknown quantity). His symptoms resolved gradually in the next 8 hours (Ward et al, 2011).
b) CASE REPORT: A 42-year-old man who was found unconscious, presented with drowsiness, a Glasgow Coma Score (GCS) of 6/15, tachycardia (heart rate 135 beats/min), hypertension (BP 187/83 mmHg) and fever (temperature 38.2 degree C). Following supportive care, his condition improved. At this time, it was found that he drank approximately 1.5 L of beer and snorted 0.75 g of "benzofury" and 0.5 g of methoxetamine before losing consciousness. He was discharged later that day (Wood et al, 2012).
c) CASE REPORT: A 29-year-old man was found catatonic with a tremor, visual hallucinations, confusion, and dilated pupils. He presented to the ED with confusion, a GCS of 14/15, tachycardia (heart rate 121 beats/min), and hypertension (BP 201/104 mmHg). Following supportive care, his symptoms improved overnight. The next day, it was found that he drank a mixture of 200 mg of methoxetamine and water before becoming unwell (Wood et al, 2012).
d) CASE REPORT: A 28-year-old man was found unconscious with a bag of methoxetamine white powder. He later developed worsening agitation and aggression. He presented to the ED with drowsiness, a GCS of 10/15, confusion, agitation, tachycardia (heart rate 113 beats/min), hypertension (BP 198/78 mmHg), and dilated pupils. He recovered following supportive care (Wood et al, 2012).
E) MOVEMENT DISORDER 1) WITH POISONING/EXPOSURE a) TILETAMINE: A 35-year-old veterinarian presented with choreatic involuntary movement of all four limbs after tiletamine abuse for 2 weeks. Laboratory drug screening test results were positive for benzodiazepine and negative for ketamine, amphetamine, and heroin. Following treatment with clonazepam, his symptoms gradually improved over the next 2 weeks. The patient still had tremors at 4-month follow-up (Lee et al, 2009).
F) SEIZURE 1) Seizures have been reported (Winters, 1972; (Felser & Orban, 1982). EEG changes may occur resembling an epileptiform EEG (Winters, 1972). Two cases of generalized clonic convulsions in children have been reported (Burmeister-Rother & StreatFeild, 1993). 2) METHOXETAMINE a) In a study of 47 methoxetamine-related telephone enquiries to NPIS (the National Poisons Information Service in UK), seizures were reported in 1 case (2.1%; 95% CI, 0 to 11) (Hill et al, 2013).
b) CASE REPORT: A 21-year-old man developed an epileptic seizure and briefly lost consciousness after inhaling vapors of heated methoxetamine powder (about 50 mg) for 2 minutes. He presented to the ED conscious and oriented. An ECG revealed sinus bradycardia and ST-segment elevation in leads DII, DIII, aVF, V4 and V5, suggesting localized myocardial ischemia. Laboratory results revealed a slightly elevated creatine kinase concentration (270 Units/L) and hyponatremia (sodium 127 mmol/L). He experienced two new seizures about 5 hours after the inhalation of methoxetamine, but his symptoms resolved following supportive care and he was transferred for addiction treatment (Imbert et al, 2014).
c) METHOXETAMINE WITH AMPHETAMINE: A 31-year-old man who had been using methoxetamine and amphetamine recreationally, presented in a deep coma, with acute respiratory failure, hyperthermia (greater than 39 degrees C), and generalized seizures. Laboratory results revealed leukocytosis (WBC 50 Units x 10(3)/L), elevated serum creatinine (2.8 mg/dL), elevated liver enzymes, and signs of massive rhabdomyolysis (CPK 170,000 Units/L). An ECG revealed sinus tachycardia (HR 120 to 140 beats/min). Despite intensive supportive care, including diuresis with alkalization, Continuous Veno-Venous Hemodialysis with citrate anticoagulation, Single Pass Albumin Dialysis for hepatic failure, his condition worsened and he died after developing multi-organ dysfunction syndrome 28 days after presentation. Serum and urine analysis revealed amphetamine concentration within the non-toxic range and methoxetamine within the toxic range (0.32 mcg/mL) (Wiergowski et al, 2014).
G) DYSTONIA 1) CASE REPORT: Tongue and neck movements which interfered with speech have been reported in a 20-year-old man 10 hours following the self-administration of 0.5 mL ketamine intravenously (Felser & Orban, 1982).
2) METHOXETAMINE: In a study of 47 methoxetamine-related telephone enquiries to NPIS (the National Poisons Information Service in UK), dissociative-type effects (eg, catatonia, dystonia, hypertonia, and tetany) were reported in 5 cases (11%; 95% CI, 5 to 23) (Hill et al, 2013).
H) NEUROPATHY 1) Polyneuropathies, a floating sensation, ataxia, dizziness, anxiety, nausea and vomiting, mental confusion, visual distortions and illusions, blurred vision, insomnia, hallucinations, vivid dreams, and slurring of speech are commonly reported in recreational users or with sub-anesthetic doses of ketamine (Felser & Orban, 1982; Ghoneim et al, 1985).
2) Decreased sexual motivation and seizures have also been reported.
I) AMNESIA 1) Low doses of ketamine (0.25-0.5 mg/kg IM) impair memory primarily through interference with memory retrieval processes. Recovery occurred within 45 and 60 minutes following administration (Ghoneim et al, 1985).
J) CLOUDED CONSCIOUSNESS 1) WITH POISONING/EXPOSURE a) In a study of acute (n=188) and chronic (n=96) toxicity of ketamine abusers (age range, 10 to 39 years) in Hong Kong, 48% (n=90) of acute cases had neurological features, including confusion, drowsiness, or transient loss of consciousness. All symptoms resolved following supportive care in 2 to 6 hours (Yiu-Cheung, 2012).
K) DIZZINESS 1) Dizziness always occurred with nausea and vomiting in one study (Ghoneim et al, 1985).
2) INTRANASAL KETAMINE: In a prospective, observational study, 40 patients (aged older than 6 years) were administered intranasal ketamine 0.5 to 0.75 mg/kg to treat pain from orthopedic injuries. Adverse effects included dizziness (n=21), feeling of unreality (n=14), nausea (n=4), fatigue (n=4), mood change (n=3), and changes in hearing (n=1) (Andolfatto et al, 2013).
L) SYNCOPE 1) WITH POISONING/EXPOSURE a) CASE REPORT: A 10-year-old had a syncopal episode approximately 5 minutes after receiving an inadvertent IM dose of ketamine (the intended drug was tetanus toxoid 0.5 Milliliter IM) (Anon, 2000). The patient was at times incoherent with no respiratory depression reported. Approximately 30 minutes after exposure the patient began to communicate. Although occasionally combative, no further symptoms were reported. A qualitative blood screen for ketamine that was returned one week later was strongly positive.
M) COMA 1) WITH POISONING/EXPOSURE a) TILETAMINE 1) CASE REPORT: A 30-year-old female animal trainer was found comatose with hypotension (BP 90/palp) after intravenous injection of an unknown amount of Telazol(R) (tiletamine hydrochloride 50 mg/mL and zolazepam hydrochloride 50 mg/mL) used as an animal anesthetic (Quail et al, 1999). The patient became alert and oriented shortly after admission following supportive care. A previous history of recreational use of Telazol(R) was reported by the patient. No permanent sequelae was reported. 2) CASE SERIES/PEDIATRICS: In a review of 9 children who had received inadvertent ketamine overdoses during procedures performed in the ED, prolonged sedation occurred in each child. The range of exposure was 5 to 100 (1 child) times the intended dose of ketamine; the children ranged in age from 24-days to 7-years-old (Green et al, 1999a). Most patients recovered within 6 hours, although in one patient sedation persisted for 24 hours. a) A 3-year-old was to receive 8 mg (0.5 mg/kg) and inadvertently was given 800 mg; elective intubation was performed as a precaution. He awoke 9 hours later with no neurological deficits reported and was discharged to home at 24 hours.
3) CASE REPORT: A 3-year-old child received 450 mg (30 mg/kg) of intramuscular ketamine instead of 45 mg during a procedure and experienced prolonged sedation (20 hours) and several episodes of airway complications (partial upper airway obstruction and a decrease in oxygen saturation to 82%), requiring repositioning of the airway and supplemental oxygen. He was discharged 36 hours after ketamine administration (Capape et al, 2008). b) KETAMINE 1) In a study of acute (n=188) and chronic (n=96) toxicity of ketamine abusers (age range, 10 to 39 years) in Hong Kong, 48% (n=90) of acute cases had neurological features, including confusion, drowsiness, or transient loss of consciousness. All symptoms resolved following supportive care in 2 to 6 hours (Yiu-Cheung, 2012).
c) METHOXETAMINE 1) Coma has been reported in patients using methoxetamine (Wood et al, 2012; Ward et al, 2011).
2) In a study of 47 methoxetamine-related telephone enquiries to NPIS (the National Poisons Information Service in UK), reduced consciousness (eg, reduced conscious level, stupor, somnolence, and coma) was reported in 8 cases (17%; 95% CI, 9 to 30) (Hill et al, 2013).
3) CASE REPORT: A 21-year-old man developed an epileptic seizure and briefly lost consciousness after inhaling vapors of heated methoxetamine powder (about 50 mg) for 2 minutes. He presented to the ED conscious and oriented. An ECG revealed sinus bradycardia and ST-segment elevation in leads DII, DIII, aVF, V4 and V5, suggesting localized myocardial ischemia. Laboratory results revealed a slightly elevated creatine kinase concentration (270 Units/L) and hyponatremia (sodium 127 mmol/L). He experienced two new seizures about 5 hours after the inhalation of methoxetamine, but his symptoms resolved following supportive care and he was transferred for addiction treatment (Imbert et al, 2014).
4) CASE REPORT: A 42-year-old man who was found unconscious, presented with drowsiness, a Glasgow Coma Score (GCS) of 6/15, tachycardia (heart rate 135 beats/min), hypertension (BP 187/83 mmHg) and fever (temperature 38.2 degree C). Following supportive care, his condition improved. At this time, it was found that he drank approximately 1.5 L of beer and snorted 0.75 g of "benzofury" and 0.5 g of methoxetamine before losing consciousness. He was discharged later that day (Wood et al, 2012).
5) CASE REPORT: A 28-year-old man was found unconscious with a bag of methoxetamine white powder. He later developed worsening agitation and aggression. He presented to the ED with drowsiness, a GCS of 10/15, confusion, agitation, tachycardia (heart rate 113 beats/min), hypertension (BP 198/78 mmHg), and dilated pupils. He recovered following supportive care (Wood et al, 2012).
6) METHOXETAMINE WITH AMPHETAMINE: A 31-year-old man who had been using methoxetamine and amphetamine recreationally, presented in a deep coma, with acute respiratory failure, hyperthermia (greater than 39 degrees C), and generalized seizures. Laboratory results revealed leukocytosis (WBC 50 Units x 10(3)/L), elevated serum creatinine (2.8 mg/dL), elevated liver enzymes, and signs of massive rhabdomyolysis (CPK 170,000 Units/L). An ECG revealed sinus tachycardia (HR 120 to 140 beats/min). Despite intensive supportive care, including diuresis with alkalization, Continuous Veno-Venous Hemodialysis with citrate anticoagulation, Single Pass Albumin Dialysis for hepatic failure, his condition worsened and he died after developing multi-organ dysfunction syndrome 28 days after presentation. Serum and urine analysis revealed amphetamine concentration within the non-toxic range and methoxetamine within the toxic range (0.32 mcg/mL) (Wiergowski et al, 2014).
N) ANXIETY 1) WITH POISONING/EXPOSURE a) METHOXETAMINE: Anxiety has been reported with methoxetamine use (Rosenbaum et al, 2012).
O) TREMOR 1) WITH POISONING/EXPOSURE a) METHOXETAMINE: In a study of 47 methoxetamine-related telephone enquiries to NPIS (the National Poisons Information Service in UK), cerebellar-type effects (eg, nystagmus, tremor) were reported in 3 cases (6%; 95% CI, 2 to 17) (Hill et al, 2013).
P) CENTRAL NERVOUS SYSTEM FINDING 1) WITH THERAPEUTIC USE a) INTRANASAL KETAMINE: In a prospective, observational study, 40 patients (aged older than 6 years) were administered intranasal ketamine 0.5 to 0.75 mg/kg to treat pain from orthopedic injuries. Adverse effects included dizziness (n=21), feeling of unreality (n=14), nausea (n=4), fatigue (n=4), mood change (n=3), and changes in hearing (n=1) (Andolfatto et al, 2013).
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Gastrointestinal |
3.8.2) CLINICAL EFFECTS
A) NAUSEA, VOMITING AND DIARRHEA 1) Nausea and vomiting have been reported following low doses (0.25 and 0.5 mg/kg) IM ketamine (Ghoneim et al, 1985).
2) METHOXETAMINE: Nausea, vomiting and diarrhea have been reported with methoxetamine use (Rosenbaum et al, 2012).
3) INTRANASAL KETAMINE: In a prospective, observational study, 40 patients (aged older than 6 years) were administered intranasal ketamine 0.5 to 0.75 mg/kg to treat pain from orthopedic injuries. Adverse effects included dizziness (n=21), feeling of unreality (n=14), nausea (n=4), fatigue (n=4), mood change (n=3), and changes in hearing (n=1) (Andolfatto et al, 2013).
B) ABDOMINAL PAIN 1) WITH POISONING/EXPOSURE a) In a study of acute (n=188) and chronic (n=96) toxicity of ketamine abusers (age range, 10 to 39 years) in Hong Kong, abdominal pain was observed in 49 (26%) acute cases. Chronic abdominal pain was observed in 63 (66%) chronic cases (Yiu-Cheung, 2012).
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Hepatic |
3.9.2) CLINICAL EFFECTS
A) INCREASED LIVER ENZYMES 1) WITH POISONING/EXPOSURE a) CASE REPORT: Mildly elevated liver enzymes have been reported in chronic oral ketamine users (Zuccoli et al, 2014).
b) CASE REPORT: A 24-year-old woman who had been using intra-nasal street ketamine regularly for the past 6 years, presented with a 6-month history of lower back pain, frequent urination, odynuria, and dysuria. Laboratory results showed renal insufficiency (urea: 19.84 mmol/L, serum creatinine: 249.3 mcmol/L), abnormal total bilirubin (22.9 mcmol/L), elevated liver enzymes, and abnormal urinalysis. Renal ultrasound revealed chronic cystitis, bilateral hydronephrosis, and ureteral expansion. Following the diagnosis of urinary tract infection, antibiotic therapy, and lack of ketamine use during hospitalization, her laboratory results normalized. However, she continued to experience urinary irritation. Cystoscopy showed a diffusely inflamed bladder with marked reduction in capacity. After the discharge, she became pregnant and 6 months after delivering her child, she started taking ketamine again. Once again, she presented with urinary irritation and laboratory results showed abnormal renal function and elevated liver enzymes. Urine protein electro-nephrosis revealed glomerular proteinuria. Magnetic resonance urography and renal ultrasound revealed bilateral hydronephrosis and ureteral expansion. Following the discontinuation of ketamine, her condition gradually resolved and all laboratory parameters normalized (Wang et al, 2014).
B) TOXIC LIVER DISEASE 1) WITH POISONING/EXPOSURE a) CASE SERIES: In a cross-sectional study of 297 ketamine abusers (by nasal insufflation; amount of ketamine used: 17.9 g +/- 16.8 g per week; duration: 82 months +/- 37 months) with urinary tract dysfunction, liver injury (all cholestatic) was observed in 9.8% of patients. Alcohol, cocaine, crystal methamphetamine, and ecstasy were also used by 149 (50%), 123 (41%), 28 (9%), 22 (7%) patients, respectively. Seven patients underwent liver biopsy, which revealed varying degrees of active bile duct injury, including biliary epithelial disarray, lymphocytic cholangitis, and ductular reaction resembling sclerosing cholangitis. Bridging fibrosis was observed in 2 patients. Magnetic resonance cholangiopancreatography examination revealed prominent or dilated common bile ducts without obstructions or extrinsic compressions in 3 of 6 patients (Wong et al, 2014).
b) CASE REPORT: A 21-year-old man with a medical history of acute renal failure and bilateral hydronephrosis, who had been using inhalational ketamine daily for at least 9 months and binging alcohol occasionally, presented with fever, marked abdominal pain, and elevated liver enzymes in the setting of acute pyelonephritis. Physical examination did not show ascites or hepatosplenomegaly. A diffusely echogenic liver with normal portal vein blood flow was noted in an abdominal ultrasound and no hepatic or bile duct abnormalities were observed in a non-contrast-enhanced abdominal computed tomography scan. His liver enzymes gradually improved following antibiotic therapy; however, he was admitted again 2 months later for recurrent pyelonephritis. Despite supportive care, his liver enzymes remained elevated on discharge. All other laboratory results, including hepatitis A, B, C, and other viral infections were normal. A percutaneous liver biopsy revealed concentric fibrosis surrounding an intrahepatic bile duct, consistent with primary or secondary sclerosing cholangitis. Interlobular bile ducts with thickened basement membranes, mild lymphocytic infiltrates, and a mild ductular reaction were also observed. Following a drug rehabilitation program, his liver enzymes improved significantly. Normal intrahepatic and extrahepatic bile ducts were observed in a follow-up magnetic resonance cholangiopancreatography (MRCP) (Turkish et al, 2013).
c) METHOXETAMINE WITH AMPHETAMINE: A 31-year-old man who had been using methoxetamine and amphetamine recreationally, presented in a deep coma, with acute respiratory failure, hyperthermia (greater than 39 degrees C), and generalized seizures. Laboratory results revealed leukocytosis (WBC 50 Units x 10(3)/L), elevated serum creatinine (2.8 mg/dL), elevated liver enzymes, and signs of massive rhabdomyolysis (CPK 170,000 Units/L). An ECG revealed sinus tachycardia (HR 120 to 140 beats/min). Despite intensive supportive care, including diuresis with alkalization, Continuous Veno-Venous Hemodialysis with citrate anticoagulation, Single Pass Albumin Dialysis for hepatic failure, his condition worsened and he died after developing multi-organ dysfunction syndrome 28 days after presentation. Serum and urine analysis revealed amphetamine concentration within the non-toxic range and methoxetamine within the toxic range (0.32 mcg/mL) (Wiergowski et al, 2014).
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Genitourinary |
3.10.2) CLINICAL EFFECTS
A) BLADDER DYSFUNCTION 1) WITH POISONING/EXPOSURE a) An association between ketamine abuse and urinary tract abnormalities has been reported (Chu et al, 2007). Severe irritative and inflammatory urinary tract and bladder symptoms (eg, cystitis) have been reported in chronic ketamine abusers (Prod Info KETALAR intravenous injection, intramuscular injection, 2012). Symptoms of ketamine cystitis include frequency, urgency, dysuria, incontinence, gross hematuria, crampy lower abdominal pain, suprapubic or pelvic pain, and urethral or vaginal jelly-like discharge (Gray & Dass, 2012). b) In a study of acute (n=188) and chronic (n=96) toxicity of ketamine abusers (age range, 10 to 39 years) in Hong Kong, lower urinary tract symptoms (ketamine cystitis) were observed in 60 (32%) acute cases. Ketamine cystitis, including dysuria, urgency, and frequency was observed in 88 (92%) chronic abusers (Yiu-Cheung, 2012). c) CASE REPORT: A 24-year-old man with a history of ketamine abuse (3 to 5 times daily for 4 years) developed severe urinary urgency and frequency. An ultrasound was used to identify bilateral hydronephrosis and a focally thickened irregular shaped bladder (Tran et al, 2014). d) CASE SERIES: Ten patients (age, 20 to 30 years) who had abused "street ketamine" for 1 to 4 years, presented with dysuria, frequency (having to void once every 15 minutes), urgency, urge incontinence, and painful hematuria. All urine cultures were negative for acid-fast bacilli. Detrusor overactivity with urinary leakage were observed in seven patients with bilateral reflux in one patient and unilateral reflux in two patients. Ultrasonography of seven patients revealed bilateral hydronephrosis. Random biopsies showed cystitis glandularis in four patients. One patient who continued to abuse ketamine after undergoing an augmentation enterocystoplasty, was readmitted 3 months later in acute renal failure. An ultrasound of the kidneys showed gross bilateral hydronephrosis (Chu et al, 2007). It is not clear if ketamine, another illicit drug, or an adulterant may have been responsible for these effects. e) CASE SERIES: Four chronic ketamine abusers (for at least a year) presented with dysuria, fluctuating lower urinary tract symptoms, lower abdominal or perineal pain, and impaired functional bladder capacities. Urinalysis revealed pyuria and microhematuria. Cystoscopic examination showed bladder ulceration with severe diffuse hemorrhage and low bladder capacity. Chronic cystitis was confirmed with a transurethral bladder mucosa biopsy . Hyaluronic acid was instilled intravesically in 3 patients. One patient could not tolerate the bladder instillation and was given oral pentosan polysulfate. Suprapubic pain was improved in 3 patients (Chen et al, 2011). f) In a study of adolescents and young adults (n=53; average age, 18 years; range, 13 to 25; mean ketamine use: 12.5 g/week; MAX: 64 g), ketamine use more than 3 times a week was associated with measurable dysfunction of the lower urinary tract (eg, lower voided volumes) and symptoms may persist for up to 1 year after the discontinuation of ketamine use. Lower urinary tract function was evaluated using the Pelvic Pain, Urgency and Frequency questionnaire, and uroflowmetry and ultrasonography. The questionnaire scores were significantly higher for patients with ketamine use for more than 24 months compared with short duration users (7.82 vs 6). These scores decreased progressively with increased abstinence duration. Ultrasound results showed hydronephrosis in 25% of active ketamine users and 5% of non-users (p = 0.062). Nine ketamine users and 2 abstainers had epigastric pain. Hematuria was reported in 3 ketamine users and 2 non-users (Mak et al, 2011). g) CASE REPORT: A 52-year-old man presented with a 10-year history of urinary urgency (20 times per day) and lower abdomen discomfort. Despite using anticholinergics and alpha-adrenergic receptor blockers for overactive bladder, benign prostatic hyperplasia, and chronic prostatitis, his urinary tract symptoms did not improve. All laboratory results were normal. Interstitial cystitis/hypersensitive bladder syndrome was suspected after using an interstitial cystitis symptom index and problem index (O'Leary and Sants). During cystoscopy procedure, mild glomerulation and mucosal bleeding in the bladder mucosal lumen were observed, suggesting a diagnosis of interstitial cystitis. A review of his medical history revealed that he had been abusing ketamine for approximately 30 years and experiencing occasional bladder pain and gross hematuria. Following the discontinuation of ketamine, his symptoms improved gradually (Nomiya et al, 2011). h) In 9 case reports, the development of ulcerative cystitis appeared to be related to the illicit use of ketamine as a recreational drug (Shahani et al, 2007). 1) The first case involved a 28-year-old man who presented with a 6-month history of dysuria, urgency, painful hematuria, and postmicturition pain which began shortly after he started using daily ketamine. A past medical history was positive for juvenile diabetes mellitus, hyperthyroidism and peptic ulcer disease. Computed tomography (CT) scans of the abdomen and pelvis showed marked inflammatory changes and a very small bladder capacity. Urine culture, urinalysis, urine cytology and vasculitis were all negative. Cystoscopy and bladder biopsy showed erythematous patches of bladder wall and eosinophilic infiltrates, respectively, both consistent with cystitis development. The patient was unresponsive to antibiotic and steroid therapy. Upon his discontinuation of ketamine, hematuria was reduced but he continued to experience urination urgency and frequency.
2) The second case involved a 25-year-old woman who presented with a 2-year history of urinary urgency, frequency and suprapubic discomfort; onset of symptoms was associated with her initial ketamine use. Cystoscopy showed mild squamous metaplasia and ulcerated patches of bladder wall. Upon ketamine cessation, the patient noted marked improvements in her symptoms.
3) A third patient, a 17-year-old boy, presented with recurrent episodes of dysuria and irritative voiding, which had occurred over several months and was associated with his ketamine use. Cystoscopy results were similar to the first case and discontinuation of ketamine had no effect on symptoms. After several unsuccessful therapy attempts to improve his symptoms, the addition of pentosan polysulfate therapy helped relieve his irritative voiding symptoms.
4) The remaining 6 cases all showed similar patterns of ketamine use, with symptoms and findings similar to the first case. Three of these 6 patients had bladder biopsies performed, which showed variable degrees of eosinophilic infiltrates. All found some benefit with the discontinuation of ketamine and the initiation of pentosan polysulfate therapy. The author hypothesized that perhaps ketamine and/or its active metabolites, norketamine and hydroxynorketamine, which accumulate in the urine, may induce bladder ulceration. In addition, despite the presence of eosinophilic infiltrates in the biopsies of these case reports, the histologic characteristics of this sort of cystitis appear to be distinct from what is described as classic eosinophilic cystitis (Shahani et al, 2007).
i) It has been suggested that ketamine cystitis may have been caused by 4 possible mechanisms: Direct toxic effect of ketamine or its metabolites on the urinary tract; microvascular damage to the urinary tract; autoimmune effects; or unrecognized bacteriuria (Gray & Dass, 2012). B) RENAL INFARCTION 1) WITH POISONING/EXPOSURE a) CASE REPORT: A 20-year-old woman presented with a 3-week history of left flank pain. On presentation, she had no fever, dysuria, hematuria, or difficulty in micturition. All laboratory tests were normal. She was a ketamine abuser who had been using ketamine by nasal insufflation about 2 to 5 grams/day. She discontinued using ketamine a year before presentation because of ketamine cystitis, but restarted using it 2 months before presentation. A CT scan of the abdomen revealed several wedge-shaped, heterogeneous areas with reduced enhancement of the left kidney, in addition to hydroureteronephrosis, indicating renal infarction. Cystoscopy revealed multiple petechial hemorrhages of the bladder wall and multiple erythematous patches with bleeding, indicating ketamine cystitis. Following supportive care, including treatment with a low-molecular-weight heparin for 3 days, followed by oral warfarin, her condition gradually improved and she was discharged 6 days after presentation. She continued to use ketamine and presented 9 months later with weakness and poor renal function. At this time, a CT scan of the abdomen revealed progressive renal infarction of the left kidney. It is proposed that the etiology of renal infarction may be secondary to vasospasm from ketamine induced decreased intracellular nitric oxide (NO) production (Chen et al, 2013).
C) OBSTRUCTIVE NEPHROPATHY 1) WITH POISONING/EXPOSURE a) CASE REPORT: A 24-year-old woman who had been using intra-nasal ketamine regularly for the past 6 years, presented with a 6-month history of lower back pain, frequent urination, odynuria, and dysuria. Laboratory results showed renal insufficiency (urea: 19.84 mmol/L, serum creatinine: 249.3 mcmol/L), abnormal total bilirubin (22.9 mcmol/L), elevated liver enzymes, and abnormal urinalysis. Renal ultrasound revealed chronic cystitis, bilateral hydronephrosis, and ureteral expansion. Following the diagnosis of urinary tract infection, antibiotic therapy, and lack of ketamine use during hospitalization, her laboratory results normalized. However, she continued to experience urinary irritation. Cystoscopy showed a diffusely inflamed bladder with marked reduction in capacity. After the discharge, she became pregnant and 6 months after delivering her child, she started taking ketamine again. Once again, she presented with urinary irritation and laboratory results showed abnormal renal function and elevated liver enzymes. Urine protein electro-nephrosis revealed glomerular proteinuria. Magnetic resonance urography and renal ultrasound revealed bilateral hydronephrosis and ureteral expansion. Following the discontinuation of ketamine, her condition gradually resolved and all laboratory parameters normalized (Wang et al, 2014).
D) ACUTE RENAL FAILURE SYNDROME 1) WITH POISONING/EXPOSURE a) METHOXETAMINE WITH AMPHETAMINE: A 31-year-old man who had been using methoxetamine and amphetamine recreationally, presented in a deep coma, with acute respiratory failure, hyperthermia (greater than 39 degrees C), and generalized seizures. Laboratory results revealed leukocytosis (WBC 50 Units x 10(3)/L), elevated serum creatinine (2.8 mg/dL), elevated liver enzymes, and signs of massive rhabdomyolysis (CPK 170,000 Units/L). An ECG revealed sinus tachycardia (HR 120 to 140 beats/min). Despite intensive supportive care, including diuresis with alkalization, Continuous Veno-Venous Hemodialysis with citrate anticoagulation, Single Pass Albumin Dialysis for hepatic failure, his condition worsened and he died after developing multi-organ dysfunction syndrome 28 days after presentation. Serum and urine analysis revealed amphetamine concentration within the non-toxic range and methoxetamine within the toxic range (0.32 mcg/mL) (Wiergowski et al, 2014).
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Dermatologic |
3.14.2) CLINICAL EFFECTS
A) EXCESSIVE SWEATING 1) WITH POISONING/EXPOSURE a) METHOXETAMINE: In a study of 47 methoxetamine-related telephone enquiries to NPIS (the National Poisons Information Service in UK), stimulant-type effects (eg, tachycardia, hypertension, mydriasis, palpitation, increased sweating) were reported in 17 cases (36%; 95% CI, 24 to 50) (Hill et al, 2013).
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Musculoskeletal |
3.15.2) CLINICAL EFFECTS
A) INCREASED MUSCLE TONE 1) Rigidity was a frequent patient complaint in a retrospective chart review of 20 ketamine abusers (Weiner, 1998).
B) RHABDOMYOLYSIS 1) In a retrospective review of 20 reported cases of ketamine abuse, 2 combative patients developed mild rhabdomyolysis (Weiner et al, 2000).
2) METHOXETAMINE WITH AMPHETAMINE: A 31-year-old man who had been using methoxetamine and amphetamine recreationally, presented in a deep coma, with acute respiratory failure, hyperthermia (greater than 39 degrees C), and generalized seizures. Laboratory results revealed leukocytosis (WBC 50 Units x 10(3)/L), elevated serum creatinine (2.8 mg/dL), elevated liver enzymes, and signs of massive rhabdomyolysis (CPK 170,000 Units/L). An ECG revealed sinus tachycardia (HR 120 to 140 beats/min). Despite intensive supportive care, including diuresis with alkalization, Continuous Veno-Venous Hemodialysis with citrate anticoagulation, Single Pass Albumin Dialysis for hepatic failure, his condition worsened and he died after developing multi-organ dysfunction syndrome 28 days after presentation. Serum and urine analysis revealed amphetamine concentration within the non-toxic range and methoxetamine within the toxic range (0.32 mcg/mL) (Wiergowski et al, 2014).
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Endocrine |
3.16.2) CLINICAL EFFECTS
A) DIABETES INSIPIDUS 1) WITH THERAPEUTIC USE a) CASE REPORT: A 2-year-old girl with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and stable hypertrophic cardiomyopathy, who was admitted for pneumonia, developed acute respiratory failure requiring intubation and mechanical ventilation. Despite treatment with lorazepam, fentanyl, and dexmedetomidine to maintain sedation, optimal sedation was ultimately maintained by ketamine (an initial bolus infusion [1 mg/kg] followed by a continuous infusion [1 mg/kg/hr]). She developed polyuria (urine output 8 mL/kg/hr) 7 hours after ketamine administration. Laboratory results (obtained 10 hours after receiving ketamine) revealed hypernatremia, elevated serum osmolality, and decreased urine osmolality, indicating a diagnosis of diabetes insipidus. Following supportive care, including vasopressin therapy, her condition gradually resolved. It was suggested that ketamine antagonized N-methyl-D-aspartate receptors, resulting in the inhibition of glutamate-stimulated arginine vasopressin release from the neurohypophysis (Hatab et al, 2014).
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Reproductive |
3.20.1) SUMMARY
A) Ketamine crosses the placenta. Severe adverse effects on the infant, including respiratory depression, have been reported following ketamine use for obstetric analgesia.
3.20.2) TERATOGENICITY
A) CONGENITAL ANOMALY 1) RAT - Kochhar et al (1986) demonstrated dose-related degeneration of fetal heart, liver, and kidney tissue in rats given IP ketamine on days 1 through 15 of gestation in doses of 25, 50 and 100 mg/kg.
2) MICE - In one study, decreases in fetal weight and length, a higher frequency of skeletal defects, and CNS abnormalities were found in mice dosed with a combination of cocaine and ketamine, as compared to groups dosed with either drug alone (Abdel-Rahman & Ismail, 2000).
3.20.3) EFFECTS IN PREGNANCY
A) PLACENTAL BARRIER 1) HUMAN - Ketamine crosses the placenta. Severe adverse effects on the infant, including respiratory depression, have been reported following ketamine use for obstetric analgesia (Janeczko et al, 1974; Downing et al, 1976).
2) RAT - Ketamine decreases rat placental circulation and uterine motility (Kochhar et al, 1986).
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