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REVIEW ARTICLE
Year : 2015  |  Volume : 5  |  Issue : 4  |  Page : 135-140

Rave drugs and anesthesiology practice: A pharmacoclinical review


1 Department of Anaesthesiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Anaesthesiology and Intensive Care, Gian Sagar Medical College And Hospital, Banur, Punjab, India

Date of Web Publication19-Oct-2015

Correspondence Address:
Sukhminder Jit Singh Bajwa
House No - 27-A, Ratan Nagar, Tripuri, Patiala - 147 001, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2231-0738.167498

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   Abstract 

Rave drugs are a class of synthetic drugs that are becoming increasingly popular among the adolescents and youths, especially those who participate in parties where the use of these drugs is rampant. Because of the wrong perception regarding their ability to increase sociability, energy, and safety, they are being extensively abused and are making alarming inroads in the Indian social scenario too. Anesthesiologists can expect to come across rave drug users in their clinical practice. Considering the settings in which rave parties are held, it is likely that anesthesiologists will have to deal with rave drug users in emergency situations. However, it is possible for anesthesiologists to come across such patients who are posted for elective surgeries too. This review attempts to increase awareness among anesthesiologists about the emerging societal menace of rave drugs and their pharmacological characteristics, their effects on various organ systems, and their associated anesthetic interactions.

Keywords: Ecstasy, ephedrine, ketamine, rave drugs


How to cite this article:
Haldar R, Bajwa SJ. Rave drugs and anesthesiology practice: A pharmacoclinical review. Int J Nutr Pharmacol Neurol Dis 2015;5:135-40

How to cite this URL:
Haldar R, Bajwa SJ. Rave drugs and anesthesiology practice: A pharmacoclinical review. Int J Nutr Pharmacol Neurol Dis [serial online] 2015 [cited 2020 Jul 13];5:135-40. Available from: http://www.ijnpnd.com/text.asp?2015/5/4/135/167498


   Introduction Top


Rave drugs (also known as "club" or "designer" drugs are a class of illicit drugs that has seen a tremendous spurt in popularity and use among youth since 1990 in the Western world. These drugs are made available or distributed in rave parties that are characterized by loud, electronic "techno rock" music (produced by computers with little or no vocals) and are held at obscure locations. These drugs seemingly enhance energy, friendliness, stamina, and sexual arousal and help the adolescent and young adult participants of such parties to sustain the exhausting lengthy all-night dancing sessions. Their use is independent of the variables of age, gender, sexual orientation, and race/ethnicity.[1] The explanation as to why drugs are consumed has been that they provide a subjective sense of "feeling better than well."[2] However, both the short-term and long-term physiological and psychological adverse effects of these drugs are relatively lesser known. Being illegal substances, their composition and purity are questionable. These drugs can be swallowed, drunk, snorted, or injected (most efficient and a common practice). Injecting drugs and the related high-risk behaviors increase the potential for contracting blood-borne infections like human immunodeficiency virus (HIV) infection and hepatitis (B and C) in subjects abusing these drugs.[3] Moreover, the monitoring and toxicological screening for these drugs still remain an underresearched area and thus, the hazard of this drug abuse continues to rise unchecked. There are progressive advancements in anesthetic and surgical techniques as well as the advent of modern equipment and newer drugs; the duties, responsibilities, and expectations from the anesthesiologist have seen a tremendous increase.[4] Considering the alarming frequency with which this particular threat is rising, anesthesiologists can expect to come across such patients during their normal course of practice. Thus, a basic understanding about these drugs and their short-term and long-term complications/clinical problems is warranted. This review seeks to raise awareness among anesthesiologists about common rave drugs, their pharmacological effects, and their anesthetic implications.


   Pharmacological Profile of Common Rave Drugs Top


The usual rave drugs include ecstasy, ephedrine, gamma-hydroxybutyrate (GHB), lysergic acid diethylamide (LSD), flunitrazepam, ketamine, and nitrites. Their use has been observed in a diverse patient population where there were differences in terms of age, gender, sexual orientation, and race/ethnicity.[1] These drugs have diverse pharmacological characteristics, sites of action, physical and psychological consequences, and interactions.

  • Ecstasy [3,4-methylenedioxymethamphetamine (MDMA)]: The oldest in this class of drugs, it was first synthesized in 1912 and has been used recreationally since 1970 for its stimulant and hallucinogenic properties. Street names of this drug include X, M, E XTC, Rolls, Clarity, Adam, Lover's speed, and hug drug. It is available in tablet/capsule form that can be ingested orally or crushed and snorted or dissolved and injected.[5] It is structurally related to psychostimulant methamphetamine and hallucinogen mescaline. It crosses the blood-brain barrier and stimulates both the central nervous system (CNS) and the sympathetic system by releasing serotonin, dopamine, and norepinephrine and blocking their reuptake inactivation by inhibiting monoamine oxidase (MAO).[6] Subjective feelings induced by this drug include a feeling of empathy, energy, psychomotor drive, positive mood, increased perception, and sensory awareness. Toxicity of MDMA is manifested in the form of nausea, tachycardia, hypertension, anxiety, bruxism, and fatal effects like disseminated intravascular coagulation (DIC), seizures, or death. Characteristic effects of this drug also include the alteration of body's temperature regulation capacity leading to hyperthermia that effects the renal, hepatic, and cardiovascular changes. This leads to excessive water intake that causes hyponatremia to which young women are particularly susceptible.[7] Since it interferes with its own metabolism, it can lead to the buildup of toxic levels on repeated use in a short time. As it acts on the serotonergic neurons it causes cognitive defects, memory changes, and depression. Neurotoxicity has been demonstrated in primates and the same effect may be seen in humans.[8] Routine screening for MDMA is difficult as immunoassays fail to detect it in a significant number of standardized specimens,[9] though toxicologists have now developed procedures for detection and quantification [10]
  • Ephedrine: Chemically it is an amphetamine analogue. Often sold in rave parties as herbal ecstasy. It mediates its effects through overstimulation of CNS and sympathetic overactivity. Adverse effects of this drug include tremulousness, anxiety, agitation, and palpitation. Serious events like stroke, seizures, myocardial infarction, hepatitis, and sudden death as a result of this drug abuse are also reported. Toxicological screening can give a positive test for amphetamines
  • GHB:First synthesized in 1960 as an anesthetic, GHB subsequently became popular as a recreational drug and nutritional supplement for bodybuilders.[11] Street names of this drug include G, Liquid ecstasy, Georgia Home Boy, Grievous Bodily Harm, Goop, Gib, Soap, and Nitro. It is available in the form of liquid, white powder (for dissolving in liquids), tablets, or capsules. It acts as a CNS suppressant and is structurally related to gammaaminobutyric acid (GABA).[12] Receptor sites that are highly specific for GHB are present in the hippocampus, cortex, and dopaminergic areas. GHB inhibits dopamine release and activates tyrosine hydroxylase, thereby increasing central dopaminergic stores. It is often mixed with alcohol to amplify its effects.[5] Effects include rapid loss of consciousness or onset of stupor (G-Napping) and antegrade amnesia.[13] Because of the level of incapacitation it produces, memory defects, and its rapid clearance from the body, it has attained notoriety as "date rape drug."[14] Toxic effects of this drug include sleep disorder, agitations, seizures, gastrointestinal (GI) disorders, apnea, bradycardia, and coma. It can produce dependence and withdrawal symptoms. Withdrawal symptoms are treated by benzodiazepines and trazodone (for mild symptoms) and barbiturates, high dose benzodiazepines, mood stabilizers, and antipsychotics (for severe symptoms). GHB can be detected in urinary screens but due to its short half-life (27 min), it is virtually undetectable in urine after 12 h of ingestion
  • LSD: Street names of this drug include Acid A, Strawberry, and Microdots. Low doses of this drug enhance sensations to light and sound whereas high doses produce strong emotional and visual effects that might not always be pleasant. The drug is chemically similar to serotonin and affects the dopaminergic, serotoninergic and N-methyl-D-aspartate (NMDA) receptors, though the exact mechanism is unknown. It presumably increases the glutamate levels in the cortex and causes excitation. LSD has anticholinesterase properties. It causes inhibition of monoamine oxidase (MAO) potentiating the effects of endogenous serotonin and histamine. Physical effects of this drug include mydriasis, increased wakefulness, and reduced appetite. Toxic effects include hypothermia or hyperthermia, tachycardia, frothing, and increased blood sugar levels
  • Flunitrazepam (Rohypnol): It is a benzodiazepine GABA receptor complex agonist with excellent oral bioavailability and lipophilicity. Street names of this drug include Roche, Forget Me Pills, Ropes, and Rib. It is abused for its intoxicant and relaxant effects. This drug is available in tablet or capsule form though it can be ground and snorted. It mediates its inhibitory effects by acting on the GABA receptors of the brain and spinal cord.[15] Adverse effects of this drug include somnolence, impaired psychomotor behavior, confusion, amnesia, and respiratory depression. Chronic use of this drug can produce dependence and withdrawal reactions may be present in dependent patients. Acute intoxication requires intravenous administration of flumazenil to reverse the effects. Toxicological tests can detect flunitrazepam in blood and urine up to 72 h due to quick metabolism and elimination [1]
  • Ketamine: It is a phencyclidine derivative and used as a human as well as a veterinary anesthetic. Street names of this drug include Special K, Vitamin K, Kit-Kat, and Cat. It can be taken orally, can be injected, smoked, or snorted. The psychedelic effects dissipate within 1 h. It is a NMDA receptor antagonist that binds to these receptors, decreasing the excitatory neurotransmitter release. It also increases dopamine release in the prefrontal cortex and midbrain. Suggested mechanisms also include decreased reuptake of dopamine, serotonin, and norepinephrine through unclear mechanisms.[16] Acute adverse effects include tachycardia, hypertension, palpitation, respiratory depression, apnoea, and unintentional injuries (due to decreased pain sensitivity). Cognitive defects in attention, memory, and learning and development of tolerance are seen among chronic abusers. Serious complications from this drug abuse include hyperthermia, seizures, rhabdomyolysis, and myoglobinuria
  • Nitrites (amyl, butyl, and isobutyl): They are available as volatile, clear amber-colored liquids. They are popular drugs in the rave circuits for their rapid onset of psychoactive and physical effects that include a sense of "high," slowed sense of time, and a carefree sense of physical well-being. They are available in glass ampoules that are crushed by fingers and then inhaled. Their effects are apparent in seconds and it dissipates within 3-5 min. These drugs are potent vasodilators and were used originally as antianginal drugs. Acute adverse effects include headache, syncope, postural hypotension, increased intraocular pressure, and tachycardia. Additional risk of life-threatening arrhythmias, loss of consciousness, or severe glaucoma exists. A serious complication from this drug abuse is methemoglobinemia that occurs due to oxidation of hemoglobin in red blood cells.



   Anesthetic Considerations in Rave Drug Users Top


Anesthesiologists are increasingly encountering patients who are rave drug users in surgical and critical care. The anesthesiologist's role in the face of this menace is significant and includes

  • The detection of addictive behavior and recognition of the clinical effects of these drugs
  • Ensuring safe conduct of anesthesia in patients with acute toxicity and in chronic abusers
  • Management of rave drug-related emergencies
  • Education and the spreading of awareness.


The anesthesiologist can encounter rave drug abusers in the settings of emergency surgeries (road traffic accidents and physical or sexual assaults) or a variety of elective surgeries. Considering the isolated locations where raves are held, the age group of users and their activities, it is likely that persons of this group will be admitted in an emergency situation.


   Preoperative Management Strategies Top


If the history of casual drug abuse is elicited beforehand, it can be of immense help in planning a safe anesthetic procedure. However, identification of potential abusers can be aided by subtle clinical signs during physical examination that helps in raising the clinical degree of suspicion regarding chronic drug usage. Crusty skin lesions on exposed areas like the nose, mouth, and lips and the presence of dermatitis or chemical burns are common among nitrite users. Moreover, chronic respiratory irritation due to nitrites can lead to coughing, wheezing, and dyspnea. MDMA-induced hepatotoxicity can give rise to progressive jaundice and weight loss. Hyperpyrexia and dehydration can occur with acute intoxication due to MDMA. Slurred speech, anxiety, agitation, psychotic behavior, and emaciated look are common features observed in chronic abusers.

History should include whether a single or multiple drugs are abused. Also the route (whether inhalational, intranasal, oral, or intravenous) needs to be known. A history of drug abuse is considered as a contraindication to day care surgery. Parturients consuming amphetamine-like substances can pose a diagnostic dilemma as hypertension and proteinuria with or without seizures can mimic preeclampsia or eclampsia.[17] Local, regional, or neuraxial techniques should be considered whenever feasible.[18]

Baseline investigations as per the clinical situation and type of surgery are needed. However, certain investigations are specific to this class of patients that are as follows:

  • Serum electrolytes: MDMA users are prone to pronounced hyponatremia. This is due to MDMA-induced antidiuretic hormone secretion or excessive water intake to counter dehydration. Serum sodium levels, volume status, urine osmolarity, and electrolytes are needed to be assessed. Based on the volume status, hyponatremia correction using normal saline or hypertonic saline should be considered. Hyperkalemia can develop secondary to rhabdomyolysis and precipitate arrhythmias
  • Liver function tests: Hepatotoxicity is a known side effect of MDMA and ephedrine use. Patients may present with transaminitis and raised prothrombin time.
  • Urinalysis: It can detect the presence of myoglobinuria. Rhabdomyolysis (due to hyperthermia, prolonged dancing, or seizures) can lead to proteinuria and elevated creatine kinase levels. This mandates vigorous hydration and forced dieresis with careful attention to fluid, electrolytes, and renal status


  • Cardiovascular status: Chronic users have a higher baseline pulse rate and blood pressure due to blockade of norepinephrine uptake. Underlying cardiac pathologies like left ventricular hypertrophy (cardiac myocyte hypertrophy), decreased left ventricular compliance due to fibrosis (long-term exposure to catecholamines, and enhanced collagen), dysrhythmias, coronary vasospasm, cardiomyopathies, and autonomic dysfunction may coexist. Cardiological assessment is thus helpful to rule out these defects
  • Viral markers: It reveals high incidence of needle-borne infections in patients who are intravenous drug abusers.



   Intraoperative Issues in Club Drug Users Top


  • Preoperative benzodiazepines can help in anxiolysis and can increase the seizure thresholds in conscious patients
  • Establishing venous access may be challenging in intravenous drug users as superficial veins may be thrombosed. It can be fatal in emergency situations where alternative accesses like jugular or intraosseous accesses need to be considered
  • Ketamine as an induction agent is to be avoided as it causes catecholamine release from potentially exhausted stores with unpredictable and undesirable effects. Induction agents like propofol and thiopentone can be used. Etomidate has stable hemodynamic effects but it may induce myoclonus and seizures
  • Airway concerns exist as bruxism that might complicate intubation. Abusing the drugs through nasal routes and intranasal intubation can cause septal trauma. Therefore, possibilities are always there that can account for seepage of blood into the aerodigestive tract. The aspiration of blood into trachea and digestive tract has its own set of complications (like higher postoperative nausea and vomiting) and involves different management strategies.[19] Cautious use of succinylcholine is advocated to avoid effects like malignant hyperthermia, raised intracranial pressure (ICP), and worsened hyperkalemia, if present. Effects of succinylcholine can be prolonged due to anticholinesterases inhibition in LSD users. Nondepolarizers like rocuronium are helpful as they aid in rapid sequence intubation, slow down heat production, and maintain paralysis.[20] Exaggerated hemodynamic effects and ICP rise can occur following laryngoscopy that needs to be blunted (lignocaine, opioids etc.)
  • Cautious use of volatile anesthetics intraoperatively can avoid hyperthermia. Narcotic infusion (preferably remifentanil) lowers surgical stress and reduces the requirement for volatile agents. Minimum alveolar concentration (MAC) of inhalational anesthetics is increased. Halothane is to be avoided in view of arrhythmias
  • Opioid-related effects like analgesia and ventilatory depression may be magnified in users of hallucinogens due to their anticholinesterase properties
  • Exaggerated effects of anesthetic drugs may occur due to decreased plasma proteins and fat stores. Anesthetics hepatically metabolized and renally excreted may have prolonged effects due to fatty liver changes and renal failure (MDMA users)
  • Intraoperative use of beta blockers can lead to unopposed alpha vasoconstriction leading to hypertension and reflex bradycardia. Labetalol for control of hypertension and tachycardia is suitable for its alpha and beta blocking effects. Ephedrine for control of hypotension may not be effective due to catecholamine depletion. Phenylephrine (direct acting) and fluid infusions are required
  • Catecholamines (epinephrine, norepinephrine) administration can have exaggerated effects due to reuptake blockade
  • Invasive arterial monitoring placed prior to induction helps in the early recognition of hemodynamic swings and repeated sampling for electrolytes and blood gases [20]
  • Temperature monitoring is necessary to avoid rhabdomyolysis and DIC. Warming blankets are to be avoided and cold intravenous fluids and ice packs may be necessary to maintain normothermia
  • Vigilant monitoring for cardiac dysrhythmias (electrolyte disturbances, coronary vasospasm) and urine output (renal failure due to myoglobinuria)
  • Local anesthetics (ester type) are metabolized through plasma cholinesterase. Toxicity might result from their use due to the inhibition of plasma cholinesterase. Caution should be exercised when using epinephrine containing local anesthetic solutions. Regional anesthesia-induced hypotension should be treated cautiously with vasoconstrictors to avoid sympathetic hyperactivity.[21] Also, the altered perception and combative behavior of these patients should be considered
  • Universal precautions throughout the conduct of anesthesia should be undertaken. The potential risk of HIV, hepatitis, and other blood-borne transmission during these circumstances increases manifold from undiagnosed and unsuspected HIV-positive cases. These risks certainly increase during the performance of invasive procedures such as intubation and airway management, securing of peripheral and central vascular access, and insertion of Ryle's tube and urinary catheters.[22]



   Postoperative Concerns Top


  • Profound neurological changes may occur following recovery from anesthesia where preexisting cognitive deficits are amplified
  • Motor irritability and hallucinations (flashbacks) may be present during the recovery phase


  • The altered pain perception occurs due to µ- and κ-receptor populations; thus, the prediction of the need for analgesic is difficult. There are chances of increased use of opioids to obtain chemical gratification. Administrations of nonopioid analgesics like paracetamol or nonsteroidal anti-inflammatory drugs (NSAIDs) are encouraged. Regional techniques should be utilized whenever possible
  • Deep vein thrombosis (DVT) is common among intravenous drug abusers, especially those who use the groin veins.



   Management of Rave Drug-Related Emergencies Top


No standard treatment protocol has been identified and supportive care (based on advanced cardiac life support protocols) needs to be instituted.[23] Medicolegal notification and samples for sexually transmitted diseases (STDs), viral markers, pregnancy, and toxicological screening should sent immediately. No specific antidote for rave drugs exists except for flunitrazepam where flumazenil can be helpful in reversing toxicity. Basic management includes cardiac monitoring, pulse oximetry, urinalysis, and performance of comprehensive chemistry panel to check for electrolytes, renal toxicity, and possible underlying disorders. Seizure control (benzodiazepines) maintenance of ventilation and aspiration prophylaxis should be given priority. Recently, numerous researches have observed the delirium management with dexmedetomidine, an alpha-2 agonist.[24] Gastrointestinal decontamination using activated charcoal and a cathartic should be considered if oral intake occurs 60 min earlier. Many such drugs can potentially cause gastritis, as is commonly seen with alcohol consumption.[25] Severe hypertension can be treated with labetalol, phentolamine, or nitroprusside. Hyperthermia should be treated with external and core cooling methods (tepid water bathing, fanning). Serotonin antagonists like cyproheptadine or chlorpromazine can be considered for controlling the serotonin syndrome. Methemoglobinemia causing cyanosis due to nitrites may not respond to oxygen and requires methylene blue.[26]


   Conclusion Top


With the changing societal demographics, rave drugs have emerged as a public menace despite increasing public education and awareness. Anesthesiologists are likely to encounter patients who are rave drug users during preanesthetic checkups, emergency surgeries, or in critical care units. It is imperative that they should be cognizant of the ill effects and potential risks of these drugs. Identification of these patients (through nonjudgmental enquiry) during routine preanesthetic checkup is one of initial steps of successful management. As anesthesiologists, we need to educate our patients during preanesthetic checkup appropriately keeping in mind their varied cultural beliefs, educational level, and their environment, in consonance with the current evidence for providing quality care to our patients.[27] Lowering of stress, by improved understanding of psychological issues, will certainly optimize autonomic and adrenal functions and help in lowering the pressure and stress reaction to surgery.[28] Rehabilitation with novel drugs may also be needed in some cases as depression is a common acute effect of such a drug consumption pattern.[29] Judicious uses of anesthetic drugs and techniques, provision of adequate postoperative care, and analgesia and following universal precautions form the mainstay of anesthetic management of these patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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